bluuebunny/crossref_metadata_2025 huggingface dataset:
A Phase 1/2, Dose-Escalation Trial of Deferasirox for the Treatment of Iron Overload in HFE -Related Hereditary Hemochromatosis
Authors: Phatak Pradyumna , Brissot Pierre , Wurster Mark , Adams Paul C , Bonkovsky Herbert L. , Gross John , Malfertheiner Peter , McLaren Gordon D. , Niederau Claus , Piperno Alberto , Powell Lawrie W. , Russo Mark W. , Stoelzel Ulrich , Stremmel Wolfgang , Griffel Louis , Lynch Nicola , Zhang Yiyun , Pietrangelo Antonello
Published: July 2010

Hereditary hemochromatosis (HH) is characterized by increased intestinal iron absorption that may result in iron overload. Although phlebotomy is widely practiced, it is poorly tolerated or contraindicated in patients with anemias, severe heart disease, or poor venous access, and compliance can vary. The once-daily, oral iron chelator, deferasirox (Exjade) may provide an alternative treatment option. Patients with HH carrying the

HFE

gene who were homozygous for the Cys282Tyr mutation, serum ferritin levels of 300-2000 ng/mL, transferrin saturation ≥45%, and no known history of cirrhosis were enrolled in this dose-escalation study to characterize the safety and efficacy of deferasirox, comprising a core and an extension phase (each 24 weeks). Forty-nine patients were enrolled and received starting deferasirox doses of 5 (n = 11), 10 (n = 15), or 15 (n = 23) mg/kg/day. Adverse events were generally dose-dependent, the most common being diarrhea, headache, and nausea (n = 18, n = 10, and n = 8 in the core and n = 1, n = 1, and n = 0 in the extension, respectively). More patients in the 15 mg/kg/day than in the 5 or 10 mg/kg/day cohorts experienced increases in alanine aminotransferase and serum creatinine levels during the 48-week treatment period; six patients had alanine aminotransferase >3× baseline and greater than the upper limit of normal range, and eight patients had serum creatinine >33% above baseline and greater than upper limit of normal on two consecutive occasions. After receiving deferasirox for 48 weeks, median serum ferritin levels decreased by 63.5%, 74.8%, and 74.1% in the 5, 10, and 15 mg/kg/day cohorts, respectively. In all cohorts, median serum ferritin decreased to <250 ng/mL.

Conclusion:

Deferasirox doses of 5, 10, and 15 mg/kg/day can reduce iron burden in patients with HH. Based on the safety and efficacy results, starting deferasirox at 10 mg/kg/day appears to be most appropriate for further study in this patient population. (Hepatology 2010)
Age Dependence of Oval Cell Responses and Bile Duct Carcinomas in Male Fischer 344 Rats Fed a Cyclic Choline-Deficient, Ethionine-Supplemented Diet
Authors: Guest Ian , Ilic Zoran , Sell Stewart
Published: July 2010

The age dependence of the oval cell response and bile duct carcinomas of male F344 rats exposed to a cyclic choline deficiency-ethionine (CDE) diet (2 weeks on, 1 week off) supports the concept of loss of potential of liver stem cells to form cancers with aging. Livers of rats exposed at 3 weeks of age demonstrated a robust and widespread oval cell proliferation followed by cholangiofibrosis and bile duct metaplasia with extensive mucinous cysts throughout all lobes, and induction of cholangiocarcinomas (CCAs) in seven of eight rats. Livers of rats exposed beginning at 8 weeks of age had much less oval cell response and cholangiofibrosis with only 1 of 15 rats developing a CCA. Livers in old (10-12 months when started) rats remained virtually unaffected, with minimal oval cell proliferation, only occasional and small foci of ductular dysplasia, and none of 16 rats developed CCAs. In contrast to most published studies using uninterrupted choline deficiency plus a carcinogen, hepatocellular carcinoma (HCC) was not observed under the conditions of this study.

Conclusion:

With aging, male F344 rats exposed to cyclic CDE diet display a diminished oval cell response and fewer CCAs. The absence of HCC is possibly due to the fact that during cyclic CDE, the week off may allow putative liver stem cells to avoid death or differentiation and survive to give rise to CCAs, whereas with continuous CDE exposure, the stem cells are forced to differentiate and develop into HCCs with relatively few CCAs. Hepatology 2010
The effect of soil data resolution on hydrological processes modelling in a large humid watershed
Authors: Ye Xuchun , Zhang Qi , Viney N. R.
Published: July 2010

Hydrological process modelling depends on the data characterizing the heterogeneity of the catchment. In particular, in a large‐scale catchment, could a higher resolution of input data contribute to a more accurate result? In this study, surveyed soil data with two different spatial resolutions were used as input data for a Soil and Water Assessment Tool (SWAT) model simulation in a large humid watershed of Xinjiang River (15 535 km2) in Poyang Lake catchment in China. Simulations of stream flow, soil water storage and evapotranspiration (ET) generated using the two soil datasets were compared, and the impact of soil data resolution was analysed. The results indicate that the different resolutions of soil data have a great impact on the distribution of hydrological response units in the SWAT model, but do not lead to obvious differences in stream flow simulation. The finer resolution data produced a higher monthly soil water storage simulation than the lower‐resolution data across the watershed, while the seasonal variation of soil water content (SW) shows a close relation to the local precipitation and temperature. Results also show that the soil ET calculation method in the SWAT model is not particularly sensitive to the different resolutions of the soil maps. The implications of this study are that improvement of the resolution of soil data does not necessarily contribute to a more accurate prediction of stream flow in large‐scale watersheds. In practical studies, modellers need to select an appropriate resolution of soil data depending on the scale of watershed and the level of accuracy required, and also need to consider the principle of the model and the physical meaning of some key parameters to explain the simulation results. Copyright © 2010 John Wiley & Sons, Ltd.
Simultaneous color‐coded imaging to distinguish cancer “stem‐like” and non‐stem cells in the same tumor
Authors: Suetsugu Atsushi , Osawa Yosuke , Nagaki Masahito , Moriwaki Hisataka , Saji Shigetoyo , Bouvet Michael , Hoffman Robert M.
Published: July 2010

In this study, we demonstrate that the differential behavior, including malignancy and chemosensitivity, of cancer stem‐like and non‐stem cells can be simultaneously distinguished in the same tumor in real time by color‐coded imaging. CD133+ Huh‐7 human hepatocellular carcinoma (HCC) cells were considered as cancer stem‐like cells (CSCs), and CD133− Huh‐7 cells were considered as non‐stem cancer cells (NSCCs). CD133+ cells were isolated by magnetic bead sorting after Huh‐7 cells were genetically labeled with green fluorescent protein (GFP) or red fluorescent protein (RFP). In this scheme, CD133+ cells were labeled with GFP and CD133− cells were labeled with RFP. CSCs had higher proliferative potential compared to NSCCs in vitro. The same number of GFP CSCs and the RFP NSCCs were mixed and injected subcutaneously or in the spleen of nude mice. CSCs were highly tumorigenic and metastatic as well as highly resistant to chemotherapy in vivo compared to NSCCs. The ability to specifically distinguish stem‐like cancer cells in vivo in real time provides a visual target for prevention of metastasis and drug resistance. J. Cell. Biochem. 111: 1035–1041, 2010. © 2010 Wiley‐Liss, Inc.
High preoperative plasma fibrinogen levels are associated with distant metastases and impaired prognosis after curative resection in patients with colorectal cancer
Authors: Tang Liang , Liu Kai , Wang Junfeng , Wang Cui , Zhao Peng , Liu Jianzhong
Published: July 2010

Background

The purpose of this study was to evaluate the association between preoperative plasma fibrinogen levels on clinicopathologic parameters and overall survival in patients after curative resection with colorectal cancer.

Methods

Preoperative plasma fibrinogen levels were examined in 341 patients who underwent curative resection for colorectal cancer. Preoperative plasma fibrinogen levels were correlated with clinicopathologic findings and disease‐specific overall survival.

Results

Mean (±SD) preoperative plasma fibrinogen levels were 369.9 mg/dl (±69.1 mg/dl). Elevated plasma fibrinogen levels were associated with advanced tumor stage (P = 0.008), venous invasion (P = 0.006), and postoperative distant metastases (P < 0.001), but not with histologic grade (P = 0.232), invasion depth (P = 0.253), and lymph node involvement (P = 0.136). Multivariate analysis showed that preoperative plasma fibrinogen levels (P = 0.029), histologic grade (P = 0.001), and lymph node involvement (P = 0.001) were defined as independent prognostic factors.

Conclusions

High preoperative plasma fibrinogen levels are associated with distant metastases and impaired prognosis after curative resection in patients with colorectal cancer. J. Surg. Oncol. 2010;102:428–432. © 2010 Wiley‐Liss, Inc.
Mycobacterium tuberculosis infection in liver transplantation
Authors: Yehia Baligh R. , Blumberg Emily A.
Published: July 2010

Mycobacterium tuberculosis can cause significant infections in liver transplant candidates and recipients. Its nonspecific clinical features and prolonged growth time in culture make the diagnosis difficult, and treating tuberculosis (TB) remains challenging because of significant toxicities and drug-drug interactions. The diagnosis of a latent TB infection may be accomplished with tuberculin skin testing and with the newer interferon-γ release assays, although this infection may be underrecognized because of host factors. Latent TB should be treated, but the degree of liver failure and the likelihood of progression to active TB will dictate whether this should occur before or after transplantation. Patients who have a history of TB, have used muromonab-CD3 or anti-T lymphocyte antibodies, or have experienced allograft rejection or coinfection with cytomegalovirus, Pneumocystis
jiroveci, or Nocardia are at the greatest risk of developing active TB. Active TB in transplant patients is difficult to treat because of drug-induced hepatotoxicity and the significant interaction between rifampin and calcineurin inhibitors. In this article, we review the epidemiology, clinical features, and evaluation of transplant candidates and recipients. In addition, we offer recommendations on the appropriate diagnostic and treatment regimens for patients with latent and active TB infections. Liver Transpl 16:1129–1135, 2010. © 2010 AASLD.
Hepatic venous outflow obstruction in pediatric living donor liver transplantation using left-sided lobe grafts: Kyoto university experience
Authors: Sakamoto Seisuke , Egawa Hiroto , Kanazawa Hiroyuki , Shibata Toshiya , Miyagawa-Hayashino Aya , Haga Hironori , Ogura Yasuhiro , Kasahara Mureo , Tanaka Koichi , Uemoto Sinji
Published: July 2010

The goals of this study were to evaluate the incidence of hepatic venous outflow obstruction (HVOO) in pediatric patients after living donor liver transplantation (LDLT) using left-sided lobe grafts and to assess the therapeutic modalities used for the treatment of this complication at a single center. Four hundred thirteen primary LDLT procedures were performed with left-sided lobe grafts between 1996 and 2006. All transplants identified with HVOO from a cohort of 380 grafts with survival greater than 90 days were evaluated with respect to the patient demographics, therapeutic intervention, recurrence, and outcome. Seventeen cases (4.5%) were identified with HVOO. Eight patients experienced recurrence after the initial balloon venoplasty. Two patients finally required stent placement after they experienced recurrence shortly after the initial balloon venoplasty. A univariate analysis revealed that a smaller recipient-to-donor body weight ratio and the use of reduced grafts were statistically significant risk factors. The cases with grafts with multiple hepatic veins had a higher incidence of HVOO. In conclusion, the necessity of repeated balloon venoplasty and stent placement was related to poor graft survival. Therefore, the prevention of HVOO should be a high priority in LDLT. When grafts with multiple hepatic veins and/or significant donor-recipient size mismatching are encountered, the use of a patch graft is recommended. Stent placement should be carefully considered because of the absence of data on the long-term patency of stents and stent-related complications. New stenting devices, such as drug-eluting and biodegradable stents, may be promising for the management of HVOO. Liver Transpl 16:1207–1214, 2010. © 2010 AASLD.
A novel automatic method for monitoring Tourette motor tics through a wearable device
Authors: Bernabei Michel , Preatoni Ezio , Mendez Martin , Piccini Luca , Porta Mauro , Andreoni Giuseppe
Published: July 2010

The aim of this study was to propose a novel automatic method for quantifying motor‐tics caused by the Tourette Syndrome (TS). In this preliminary report, the feasibility of the monitoring process was tested over a series of standard clinical trials in a population of 12 subjects affected by TS. A wearable instrument with an embedded three‐axial accelerometer was used to detect and classify motor tics during standing and walking activities. An algorithm was devised to analyze acceleration data by: eliminating noise; detecting peaks connected to pathological events; and classifying intensity and frequency of motor tics into quantitative scores. These indexes were compared with the video‐based ones provided by expert clinicians, which were taken as the gold‐standard. Sensitivity, specificity, and accuracy of tic detection were estimated, and an agreement analysis was performed through the least square regression and the Bland‐Altman test. The tic recognition algorithm showed sensitivity = 80.8% ± 8.5% (mean ± SD), specificity = 75.8% ± 17.3%, and accuracy = 80.5% ± 12.2%. The agreement study showed that automatic detection tended to overestimate the number of tics occurred. Although, it appeared this may be a systematic error due to the different recognition principles of the wearable and video‐based systems. Furthermore, there was substantial concurrency with the gold‐standard in estimating the severity indexes. The proposed methodology gave promising performances in terms of automatic motor‐tics detection and classification in a standard clinical context. The system may provide physicians with a quantitative aid for TS assessment. Further developments will focus on the extension of its application to everyday long‐term monitoring out of clinical environments. © 2010 Movement Disorder Society
Adverse drug reactions to dopamine agonists: A comparative study in the french pharmacovigilance database
Authors: Perez‐Lloret Santiago , Bondon‐Guitton Emmanuelle , Rascol Olivier , Montastruc Jean‐Louis ,   and the French Association of Regional Pharmacovigilance Centers
Published: July 2010

Pharmacodynamical differences between dopamine agonists (DAs) suggest differences in their adverse drug reactions (ADRs) profile. In this study, frequencies of ADR to DAs or levodopa reports in the French Pharmacovigilance Database were explored. Reports occurring between January 1, 1984 and December 31, 2008 were selected (2,189 for DAs and 1,315 for levodopa). The numbers of ADRs by system organ class were compared using ropinirole as a reference. Diurnal somnolence was less frequently reported with all DAs when compared with ropinirole (P < 0.001). Impulse control disorders (ICDs) were more frequently reported with pramipexole (P < 0.001). Significant difference was found among DAs in the frequency of confusion or disorientation (P < 0.001), nausea and vomiting (P < 0.05), or edemas (P < 0.001). No difference among DAs was observed in the frequency of hallucination or arterial hypotension ADR reports (P = 0.3 and P = 0.1). Pleural effusions were more frequently reported with pergolide or bromocriptine (P < 0.001). Somnolence or ICD reports were less frequent with levodopa, whereas confusion was more frequently reported. In summary, our data show significant differences in the kind of ADRs reported for each DA. © 2010 Movement Disorder Society.
Early‐onset L‐dopa‐responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations
Authors: Paisán‐Ruiz Coro , Guevara Rocio , Federoff Monica , Hanagasi Hasmet , Sina Fardaz , Elahi Elahe , Schneider Susanne A. , Schwingenschuh Petra , Bajaj Nin , Emre Murat , Singleton Andrew B. , Hardy John , Bhatia Kailash P. , Brandner Sebastian , Lees Andrew J. , Houlden Henry
Published: July 2010

Seven autosomal recessive genes associated with juvenile and young‐onset Levodopa‐responsive parkinsonism have been identified. Mutations in PRKN, DJ‐1, and PINK1 are associated with a rather pure parkinsonian phenotype, and have a more benign course with sustained treatment response and absence of dementia. On the other hand, Kufor‐Rakeb syndrome has additional signs, which distinguish it clearly from Parkinson's disease including supranuclear vertical gaze palsy, myoclonic jerks, pyramidal signs, and cognitive impairment. Neurodegeneration with brain iron accumulation type I (Hallervorden‐Spatz syndrome) due to mutations in PANK2 gene may share similar features with Kufor‐Rakeb syndrome. Mutations in three other genes, PLA2G6 (PARK14), FBXO7 (PARK15), and Spatacsin (SPG11) also produce clinical similar phenotypes in that they presented with rapidly progressive parkinsonism, initially responsive to Levodopa treatment but later, developed additional features including cognitive decline and loss of Levodopa responsiveness. Here, using homozygosity mapping and sequence analysis in families with complex parkinsonisms, we identified genetic defects in the ATP13A2 (1 family), PLA2G6 (1 family) FBXO7 (2 families), and SPG11 (1 family). The genetic heterogeneity was surprising given their initially common clinical features. On careful review, we found the FBXO7 cases to have a phenotype more similar to PRKN gene associated parkinsonism. The ATP13A2 and PLA2G6 cases were more seriously disabled with additional swallowing problems, dystonic features, severe in some, and usually pyramidal involvement including pyramidal weakness. These data suggest that these four genes account for many cases of Levodopa responsive parkinsonism with pyramidal signs cases formerly categorized clinically as pallido‐pyramidal syndrome. © 2010 Movement Disorder Society.
No increased risk of obstructive sleep apnea in Parkinson's disease
Authors: Trotti Lynn Marie , Bliwise Donald L.
Published: July 2010

Pulmonary function abnormalities in Parkinson's disease (PD) might predispose patients to obstructive sleep apnea (OSA) and daytime sleepiness. Fifty‐five idiopathic PD patients (mean age = 63.9) underwent three consecutive nights of in‐laboratory polysomnography on their usual dopaminergic medications. Sleep apnea severity was compared to published, normative, population‐based data from the Sleep Heart Health Study. Demographic and clinical data were compared in patients with and without OSA. The apnea‐hyponea index (AHI) was stable across nights in PD patients, and was not different between PD patients and normative controls. Epworth Sleepiness Scale scores, Body Mass Index, and snoring did not correlate with AHI. Severity of OSA is stable across multiple nights in PD patients. Rates of OSA in PD are similar to those seen in the general population. Daytime sleepiness, snoring, and obesity may not be helpful in identifying OSA in PD. © 2010 Movement Disorder Society
Restless legs syndrome in patients with amyotrophic lateral sclerosis
Authors: Lo Coco Daniele , Piccoli Federico , La Bella Vincenzo
Published: July 2010

We aimed to evaluate the frequency and determinants of restless legs syndrome (RLS) in a group of 76 patients with amyotrophic lateral sclerosis (ALS) and 100 control subjects. A diagnosis of RLS was made according to the criteria of the International RLS Study Group, and severity was assessed by the RLS severity scale. RLS was significantly more frequent in patients with ALS (ALS/RLS+) than in control subjects (25% vs. 8%; P = 0.002). Compared with control subjects, patients with ALS/RLS+ showed shorter history of RLS complaints and higher frequency of symptoms occurrence. Moreover, compared with those without RLS, patients with ALS/RLS+ showed increased functional impairment and more often reported sleep complaints. Multivariate logistic regression confirmed the association between RLS and functional impairment. Our findings suggest that RLS should be considered as a possible cause of disrupted sleep in patients with ALS and should be specifically investigated in these patients. © 2010 Movement Disorder Society.
Randomized, double‐blind, multicenter evaluation of pramipexole extended release once daily in early Parkinson's disease
Authors: Hauser Robert A. , Schapira Anthony H.V. , Rascol Olivier , Barone Paolo , Mizuno Yoshikuni , Salin Laurence , Haaksma Monika , Juhel Nolwenn , Poewe Werner
Published: July 2010

The objective of this study was to evaluate the efficacy and safety of pramipexole extended release (ER) administered once daily in early Parkinson's disease (PD). Pramipexole immediate release (IR) administered three times daily (TID) is an efficacious and generally well‐tolerated treatment for PD. A pramipexole ER formulation is now available. We performed a randomized, double‐blind, placebo and active comparator–controlled trial in subjects with early PD. The primary efficacy and safety evaluation of pramipexole ER compared with placebo took place at week 18. Two hundred fifty‐nine subjects were randomized 2:2:1 to treatment with pramipexole ER once daily, pramipexole IR TID, or placebo. Levodopa rescue was required by 7 subjects in the placebo group (14%), 3 subjects in the pramipexole ER group (2.9%, P = 0.0160), and 1 subject in the pramipexole IR group (1.0%, P = 0.0017). Adjusted mean [standard error (SE)] change in Unified Parkinson Disease Rating Scale (UPDRS) II [activities of daily living (ADL)] + III (motor) scores from baseline to week 18, including post‐levodopa rescue evaluations, was −5.1 (1.3) in the placebo group, −8.1 (1.1) in the pramipexole ER group (P = 0.0282), and −8.4 (1.1) in the pramipexole IR group (P = 0.0153). Adjusted mean (SE) change in UPDRS ADL + motor scores, censoring post‐levodopa rescue data, was −2.7 (1.3) in the placebo group, −7.4 (1.1) in the pramipexole ER group (P = 0.0010), and −7.5 (1.1) in the pramipexole IR group (P = 0.0006). Adverse events more common with pramipexole ER than placebo included somnolence, nausea, constipation, and fatigue. Pramipexole ER administered once daily was demonstrated to be efficacious compared with placebo and provided similar efficacy and tolerability as pramipexole IR administered TID. © 2010 Movement Disorder Society
Cardiac autonomic dysfunction in idiopathic REM sleep behavior disorder
Authors: Postuma Ronald B. , Lanfranchi Paola A. , Blais Helene , Gagnon Jean‐Francois , Montplaisir Jacques Y.
Published: July 2010

More than 50% of persons with idiopathic REM sleep behavior disorder (RBD) will develop Parkinson's disease or Lewy body dementia. Symptom screens and metaiodobenzylguanine (MIBG)‐scintigraphy suggest autonomic abnormalities in idiopathic RBD, but it is unclear whether autonomic abnormalities can predict neurodegenerative disease. From a cohort of 99 patients with idiopathic RBD, we selected those who developed parkinsonism or dementia. These were matched by age, sex, and follow‐up duration to patients with RBD who remained disease free and to matched controls. From the polysomnographic trace performed at baseline evaluation, measures of beat‐to‐beat RR variability including time domains (mean RR‐interval and RR‐standard deviation) and frequency domains (low and high frequency components) were retrospectively assessed. Twenty‐one patients with idiopathic RBD who developed neurodegenerative disease were included (Parkinson's disease‐11, multiple system atrophy‐1, and dementia‐9). Age at PSG was 66 years, and 86% were male. PSG was performed on average 6.7 years before defined neurodegenerative disease. Comparing all patients with idiopathic RBD to controls, there were significant reductions in RR‐standard deviation (24.6 ± 2.2 ms vs. 35.2 ± 3.5 ms, P = 0.006), very low frequency components (238.6 ± 99.6 ms2 vs. 840.1 ± 188.3 ms2, P < 0.001), and low frequency components (127.8 ± 26.3 ms2 vs. 288.7 ± 66.2 ms2, P = 0.032). However, despite clear differences between patients with idiopathic RBD and controls, there were no differences in any measure between those who did or did not develop disease. RR‐variability analysis demonstrates substantial autonomic dysfunction in idiopathic RBD. However, this dysfunction is identical in patients who will or will not develop defined neurodegenerative disease. This suggests that autonomic dysfunction is linked with RBD independent of associated Parkinson's disease or Lewy body dementia. © 2010 Movement Disorder Society
The impact of stroke: insights from patients in Taiwan
Authors: Lee Ya‐Chen , Chen Yi‐Miau , Hsueh I‐Ping , Wang Yen‐Ho , Hsieh Ching‐Lin
Published: July 2010

Clinical stroke trials have been increasing interest in patient‐centred assessments such as functional status and health‐related quality of life. There is a consensus that these measurement factors must be relevant to, and obtained from, the patients of interest. The main purpose of this study was to evaluate the patients' reactions and concerns that individuals experience after having had a stroke. A focus group and individual interviews were conducted to identify and describe the patients' reactions to living with the results of a stroke. One hundred twelve patients participated in the study. Fifteen factors were identified as problems for the 112 participants. For the level of impact and importance, the highest percentages of responses rated by the participants in each factor were all towards the physical aspects of functioning such as hand/arm function and mobility. These findings provide important information on the impact of stroke that could be useful for occupational therapists in treatment planning and outcome measurement. Further research is recommended to understand the impact of a stroke on an individual's adjustment at home and in the community. Copyright © 2010 John Wiley & Sons, Ltd.
Solvent, salt and high pressure effects on the rate and equilibrium constants for the formation of tri‐n‐butylphosphoniumdithiocarboxylate
Authors: Iskhakova Gulnara G. , Kiselev Vladimir D. , van Eldik Rudi , Zahl Achim , Shihab Mehdi S. , Konovalov Alexander I.
Published: July 2010

Solvent, salt and high pressure effects on the rate and equilibrium constants for the formation of tri‐n‐butylphosphoniumdithiocarboxylate at 298.2 K are reported. This equilibrium is shifted to the phosphobetaine in polar solvents, salt solutions and under high external pressure. The reaction volume changes dramatically on going from less polar diethyl ether (−69 cm3 mol−1) and tetrahydrofurane (THF) (−66 cm3 mol−1), to more polar acetonitrile (−39 cm3 mol−1) and acetone (−38 cm3 mol−1). Copyright © 2010 John Wiley & Sons, Ltd.
Sickness absence and full return to work after cancer: 2‐year follow‐up of register data for different cancer sites
Authors: Roelen Corné A. , Koopmans Petra C. , Groothoff Johan W. , van der Klink Jac J. , Bültmann Ute
Published: July 2010

Objective: Cancer survival has improved in recent years, but data on return to work (RTW) after cancer are sparsely published. Therefore, this study analysed RTW after cancer.

Methods: Employees diagnosed with breast cancer, genital cancer, gastro‐intestinal cancer, lung cancer, skin cancer, or blood malignancies were selected from an occupational health register. Sickness absence was followed for 2 years after diagnosis and full RTW at equal earnings as before sickness absence was assessed for each cancer site using Cox proportional hazards regression analysis stratifying for age and gender.

Results: 3701 (73%) of 5074 employees with cancer had full RTW after a median duration of 290 days. Employees with lung cancer had the longest duration of sickness absence and only 45% of them had full RTW 2 years after diagnosis compared with 88% of employees with genital cancer and 87% of employees with skin cancer. Age was associated with the time to full RTW among employees with genital cancer: women aged⩾35 years had a longer time to full RTW compared with women <35 years and men aged⩾55 years had a longer time to full RTW compared with men <35 years. Gender was associated with the time to full RTW among survivors of blood malignancies with women having a longer time to full RTW than men.

Conclusions: Most employees had full RTW within 2 years after the diagnosis of cancer and the time to RTW was largely independent of age and gender. Copyright © 2010 John Wiley & Sons, Ltd.
Do risk factors for persistent asthma modify lung function in infants and young children with recurrent wheeze?
Authors: Keklikian Esteban , Sanchez‐Solis Manuel , Bonina Angel Jose , Meneguzzi Alejandra , Pastor‐Vivero Maria Dolores , Mondejar‐Lopez Pedro , Garcia‐Marcos Luis
Published: July 2010

Background

There is very limited information on how the risk of persistent asthma in recurrent wheezing (RW) infants modifies their lung function early in life. The aim of this study is to compare lung function of RW infants and young children with a positive or negative asthma predictive index (API), an index previously used to anticipate asthma persistence into childhood and adolescence.

Methods

Two groups of RW infants and young children were recruited in two centres in Spain (Palma de Mallorca and Murcia). Lung function was measured according to the thoracho‐abdominal compression technique (RCT), and values of the maximal flow at functional residual capacity ${\rm (V}_{{\rm maxFRC}}^{\rm '} {\rm )}$ were expressed as Z‐scores. Other variables included in the study, as independent factors, were: gender, age, length, weight, and parental smoking habits together with information regarding API.

Results

Expressed as mean ± SD, API+ RW infants (n = 50; age in months 11.9 ± 4.9) had a lower ${\rm V}_{{\rm maxFRC}}^{\rm '} $ Z‐score than API− RW ones (n = 41; age in months 12.3 ± 6.2; −2.01 ± 0.79 vs. −1.64 ± 0.77, P = 0.026, respectively). Centre and tobacco exposition did not have an effect on lung function.

Conclusion

Among RW infants and young children, those having a positive API have a significant lower lung function as measured by ${\rm V}_{{\rm maxFRC}}^{\rm '} $ at an early age. Pediatr. Pulmonol. 2010; 45:914–918. © 2010 Wiley‐Liss, Inc.
Does presenting with meconium ileus affect the prognosis of children with cystic fibrosis?
Authors: Johnson Jo‐Anne , Bush Andrew , Buchdahl Roger
Published: July 2010

It is a matter of debate as to what extent the long‐term outcome of cystic fibrosis (CF) is affected by presenting with meconium ileus (MI). We compared long‐term clinical outcomes of CF children who presented with MI, to those presenting with other symptoms (non‐MI) in an era of non new‐born‐screening (NBS).

We collected annual lung function data between the ages of 8–15 years in terms of percent predicted first second forced expired volume (FEV1%pr), percent predicted forced vital capacity (FVC%pr), and between the ages of 2–15 years annual height and weight Z‐scores (HtZ and WtZ respectively) for children attending the Royal Brompton Hospital CF clinic. To be included in the study, subjects had to have at least five pulmonary function tests and five anthropometric measurements recorded over this period.

Thirty‐eight MI and 76 non‐MI subjects were compared. There were no significant differences in genotype, sex, chronic Pseudomonas infection, or pancreatic enzyme use between the two groups. The median age of diagnosis was 1 day (MI) versus 7 months (non‐MI). There was a decline in spirometry and anthropometric variables over the study period for both MI and non‐MI groups apart from WtZ score in the non‐MI group. Mixed model analysis adjusting for potential confounders including genotype, pancreatic status, sex, chronic Pseudomonas aeruginosa lung infection, and age of diagnosis revealed no difference between the two groups in terms of lung function and growth during the time period of the study, however there was a non‐significant trend for subjects presenting with MI to do better in all four parameters.

We conclude that babies presenting with MI have no worse long‐term outcome than those presenting symptomatically later in infancy, despite having undergone invasive procedures in the newborn period. This underscores the importance of early diagnosis and treatment in CF. Pediatr Pulmonol. 2010; 45:951–958. © 2010 Wiley‐Liss, Inc.
Development of a new dispenser for microbiological control agents and evaluation of dissemination by bumblebees in greenhouse strawberries
Authors: Mommaerts Veerle , Put Kurt , Vandeven Jessica , Jans Kris , Sterk Guido , Hoffmann Lucien , Smagghe Guy
Published: July 2010

BACKGROUND: To date, in modern agriculture, biological control strategies are increasingly becoming the preferred pest management approach. However, the success of microbiological control agents (MCAs) largely depends on efficient dissemination into the crop. The pollinator‐and‐vector technology employs pollinating insects like bees for a better dissemination. In this study, a new dispenser for bumblebee workers of Bombus terrestris L. was developed. Binab‐T‐vector and Prestop‐Mix were used as two typical MCA products for dissemination.

RESULTS: In a first series of experiments in the laboratory for optimisation, the newly developed dispenser was a two‐way type dispenser, 20 cm long, with two rectangular compartments and different entrance and exit holes. In addition, the amounts of MCA loaded on the workers were 10 times higher with the new dispenser as compared with the side‐by‐side passageway (SSP) dispenser. Typically, the highest amounts were recovered from the thorax and legs of the workers. In a second series of experiments under greenhouse conditions with the use of queen‐right B. terrestris hives, successful dissemination in strawberry flowers was obtained at different distances from the hive (0–8 m, 8–18 m and 18–21 m), and the workers inoculated the first, second and third flowers that were consecutively visited. In addition, the new dispenser caused no adverse effects on worker foraging intensity, whereas a dramatic reduction was scored with an SSP dispenser. Finally, the data suggested that it is necessary to refill the newly developed dispenser at 3 day intervals.

CONCLUSIONS: The results demonstrated that, with the use of the newly developed dispenser, bumblebee workers carried high amounts of MCA, and this resulted in a successful dissemination of MCA into strawberry flowers. Copyright © 2010 Society of Chemical Industry
Construction by replacement: a new approach to simulation modeling
Authors: Hines James , Malone Thomas , Gonçalves Paulo , Herman George , Quimby John , Murphy‐Hoye Mary , Rice James , Patten James , Ishii Hiroshi
Published: July 2010

Simulation modeling can be valuable in many areas of management science, but it is often costly, time‐consuming, and difficult to do. To reduce these problems, system dynamics researchers have previously developed standard pieces of model structure, called molecules, that can be reused in different models. However, the models assembled from these molecules often lacked feedback loops and generated few, if any, insights. This paper describes a new and more promising approach to using molecules in system dynamics modeling. The heart of the approach is a systematically organized library (or taxonomy) of predefined model components, or molecules, and a set of software tools for replacing one molecule with another. Users start with a simple generic model and progressively replace parts of the model with more specialized molecules from a systematically organized library of predefined components. These substitutions either create a new running model automatically or request further manual changes from the user. The paper describes our exploration using this approach to construct system dynamics models of supply chain processes in a large manufacturing company. The experiment included developing an innovative “tangible user interface” and a comprehensive catalog of system dynamics molecules. The paper concludes with a discussion of the benefits and limitations of this approach. Copyright © 2010 System Dynamics Society.
CFD Benchmark for a Single Strand Tundish (Part II)
Authors: Odenthal H.‐J. , Javurek M. , Kirschen M. , Vogl N.
Published: July 2010

In a comparative benchmark, nine participants of the German Steel Institute VDEh working group “Fluid Mechanics and Fluid Simulation” studied the melt flow in a 16‐t single‐strand tundish. Starting with a steady‐state simulation of the melt flow, the transient flow behaviour was simulated for an idealized ladle change involving a sudden jump in temperature and concentration. In addition, the separation of non‐metallic particles to the melt surface was examined. No guidelines and limitations were made regarding the simulation strategy. The predicted flow profiles, temperature and concentration distributions coincide with each other within a good approximation. Systematic differences in the transient temperature and turbulence fields are explained by the selection of the boundary condition at the free surface. All CFD programs reproduce the fundamental flow structure with a good degree of accuracy. The separation rate for non‐metallic particles calculated on the basis of the Lagrange Method are greater than would be expected according to theory and measurement results obtained on the water model.
NY‐ESO‐1 protein glycosylated by yeast induces enhanced immune responses
Authors: Wadle Andreas , Mischo Axel , Strahl Sabine , Nishikawa Hiroyoshi , Held Gerhard , Neumann Frank , Wullner Beate , Fischer Eliane , Kleber Sascha , Karbach Julia , Jager Elke , Shiku Hiroshi , Odunsi Kunle , Shrikant Protul A. , Knuth Alexander , Cerundolo Vincenzo , Renner Christoph
Published: July 2010

Vaccine strategies that target dendritic cells to elicit potent cellular immunity are the subject of intense research. Here we report that the genetically engineered yeast Saccharomyces cerevisiae, expressing the full‐length tumour‐associated antigen NY‐ESO‐1, is a versatile host for protein production. Exposing dendritic cells (DCs) to soluble NY‐ESO‐1 protein linked to the yeast a‐agglutinin 2 protein (Aga2p) protein resulted in protein uptake, processing and MHC class I cross‐presentation of NY‐ESO‐1‐derived peptides. The process of antigen uptake and cross‐presentation was dependent on the glycosylation pattern of NY‐ESO‐1‐Aga2p protein and the presence of accessible mannose receptors. In addition, NY‐ESO‐1‐Aga2p protein uptake by dendritic cells resulted in recognition by HLA‐DP4 NY‐ESO‐1‐specific CD4+ T cells, indicating MHC class II presentation. Finally, vaccination of mice with yeast‐derived NY‐ESO‐1‐Aga2p protein led to an enhanced humoral and cellular immune response, when compared to the bacterially expressed NY‐ESO‐1 protein. Together, these data demonstrate that yeast‐derived full‐length NY‐ESO‐1‐Aga2p protein is processed and presented efficiently by MHC class I and II complexes and warrants clinical trials to determine the potential value of S. cerevisiae as a host for cancer vaccine development. Copyright © 2010 John Wiley & Sons, Ltd.
Disiloxanediolates and Metallasilsesquioxanes of the Rare Earth Elements
Authors: Lorenz Volker , Edelmann Anja , Gießmann Stephan , Hrib Cristian G. , Blaurock Steffen , Edelmann Frank T.
Published: July 2010

This research report summarizes recent results in the chemistry of lanthanide disiloxanediolates and metallasilsesquioxanes. Both classes of compounds can be regarded as realistic model compounds for silica‐supported lanthanide catalysts.
The physiological advantage of an ecological filter species, Indocalamus longiauritus, over co‐occurring Fagus lucida and Castanopsis lamontii seedlings
Authors: Bai Kundong , Jiang Debing , Cao Kunfang , Liao Debao , Wan Xianchong
Published: July 2010

Indocalamus longiauritus (a dwarf bamboo) dominates forest understory and functions as an ecological filter to hinder the regeneration of canopy tree species in many temperate forests. However, the physiological mechanism underlying the function of ecological filters is not clear. In this study, we measured leaf‐level carbon capture ability and use efficiency of the dwarf bamboo and the co‐existing Fagus lucida (beech) and Castanopsis lamontii (chinkapin) seedlings in forest understory and small gaps in a beech–chinkapin mixed forest in the summer of 2005. The results indicated that I. longiauritus exhibited greater carbon capture ability, as indexed by light‐saturated photosynthetic rate (Pmax), maximal carboxylation rate, maximal electron transport rate and carboxylation efficiency, than the co‐occurring F. lucida and C. lamontii seedlings in both forest understory and small gaps. Higher carbon capture ability in I. longiauritus was related to its greater partition of absorbed light energy to photochemistry. I. longiauritus had higher photosynthetic nitrogen use efficiency than F. lucida and C. lamontii seedlings in both light environments. However, water use efficiency (WUE) in I. longiauritus was higher than F. lucida but lower than C. lamontii. This intermediate WUE in I. longiauritus was related to its intermediate light‐saturated stomatal conductance. In addition, I. longiauritus reduced metabolic cost by increasing the ratio of Pmax to respiration rate, leading to increased net carbon balance. On the other hand, F. lucida and C. lamontii seedlings had greater plasticity of carbon capture ability and leaf structural traits, which might facilitate colonization of gaps and realization of natural regeneration in these species.
Nature of motor imitation problems in school‐aged males with autism: how congruent are the error types?
Authors: Vanvuchelen Marleen , Roeyers Herbert , De Weerdt Willy
Published: July 2010

This case—comparison study explores the underlying mechanisms of imitation problems in school‐aged males with autism. Analysis of congruent error types in their imitation performance was made and compared with appropriate comparisons. Fifty‐five males (eight low‐functioning with autism: mean age 6y 2mo [SD 7.6mo]; 13 low‐functioning with learning disabilities: mean age 6y 3mo [SD 2.8mo]; 17 high‐functioning with autism: mean age 8y 9mo [SD 11mo]; and 17 typically developing: mean age 8y 8mo [SD 11.6mo]) were assessed on 18 single gestures and six sequences of hand postures. Imitation performance was videotaped for blind scoring on 21 possible errors by two independent observers. Results revealed that in both groups with autism, imitation required far more effort (more attempts) than in the comparison groups and was less precise (more spatial errors). Typical for low‐functioning participants with autism was their less mature imaginary grip in transitive gestures. Typical for high‐functioning participants with autism was their preference for immature mirror‐image imitations. These observations support the assumption that the underlying mechanisms in motor imitation problems are linked more to the action production system and less to the action conceptual system or to behavioural problems. We postulate that the action production system is delayed rather than deficient.
Metacognitions in Desire Thinking: A Preliminary Investigation
Authors: Caselli Gabriele , Spada Marcantonio M.
Published: July 2010

Background: Desire thinking is defined as a voluntary thinking process orienting to prefigure images, information and memories about positive target-related experience. Recent research has highlighted the role of desire thinking in the maintenance of addictive, eating and impulse control disorders. Currently little is known about metacognitions in desire thinking. Aim: To investigate: (1) the presence and content of desire thinking during a desire experience; (2) the presence of metacognitive beliefs in desire thinking; (3) the goal of desire thinking; (4) attentional focus during desire thinking; and (5) the impact of desire thinking on craving. Method: Twenty-four individuals with a diagnosis of either alcohol abuse, bulimia nervosa, pathological gambling or smoking dependence were assessed using a semi-structured interview. Results: Findings indicated that participants engaged in desire thinking and endorsed both positive and negative metacognitive beliefs about this process. The goal of desire thinking was to regulate internal states. Participants also reported that during a desire experience their attentional focus was continuously shifting between internal state and external context and that engaging in desire thinking increased craving. Conclusions: These findings provide preliminary evidence that metacognitions play a role in desire thinking.
Topographically induced height errors in predicted atmospheric loading effects
Authors: van Dam T. , Altamimi Z. , Collilieux X. , Ray J.
Published: July 2010

Atmospheric pressure variations are known to induce vertical displacements of the Earth's surface with magnitudes large enough to be detected by geodetic observations. Estimates of these loading effects are derived using global reanalysis fields of surface pressure as input. The input surface pressure has a minimum spatial sampling, which does not capture true surface pressure variations due to high topographic variability in some regions. In this paper, we investigate the effect that unmodeled topographic variability has on surface pressure estimates and subsequent estimates of vertical surface displacements. We find that the estimated height changes from the topographic surface pressure can be significant (2–4 mm) for sites in regions of high topographic variability. When we compare the estimated height changes to Global Positioning System residuals from the 2005 International Terrestrial Reference Frame Realization, we find that the heights derived from the topographic surface pressure, versus those from the normal surface pressure, perform better at reducing the scatter on the height coordinate time series.