bluuebunny/crossref_metadata_2025 huggingface dataset:
Pressure effects on water vapour lines: beyond the Voigt profile
Authors: Ngo N. H. , Tran H. , Gamache R. R. , Hartmann J. M.
Published: April 2012

A short overview of recent results on the effects of pressure (collisions) regarding the shape of isolated infrared lines of water vapour is presented. The first part of this study considers the basic collisional quantities, which are the pressure-broadening and -shifting coefficients, central parameters of the Lorentzian (and Voigt) profile and thus of any sophisticated line-shape model. Through comparisons of measured values with semi-classical calculations, the influences of the molecular states (both rotational and vibrational) involved and of the temperature are analysed. This shows the relatively unusual behaviour of H
2
O broadening, with evidence of a significant vibrational dependence and the fact that the broadening coefficient (in cm
−1
atm
−1
) of some lines increases with temperature. In the second part of this study, line shapes beyond the Voigt model are considered, thus now taking ‘velocity effects’ into account. These include both the influence of collisionally induced velocity changes that lead to the so-called Dicke narrowing and the influence of the dependence of collisional parameters on the speed of the radiating molecule. Experimental evidence of deviations from the Voigt shape is presented and analysed. The interest of classical molecular dynamics simulations, to model velocity changes, together with semi-classical calculations of the speed-dependent collisional parameters for line-shape predictions from ‘first principles’, are discussed.
Use of influenza A viruses expressing reporter genes to assess the frequency of double infections in vitro
Authors: Bodewes R. , Nieuwkoop N. J. , Verburgh R. J. , Fouchier R. A. M. , Osterhaus A. D. M. E. , Rimmelzwaan G. F.
Published: April 2012

Exchange of gene segments between mammalian and avian influenza A viruses may lead to the emergence of potential pandemic influenza viruses. Since co-infection of single cells with two viruses is a prerequisite for reassortment to take place, we assessed frequencies of double-infection in vitro using influenza A/H5N1 and A/H1N1 viruses expressing the reporter genes eGFP or mCherry. Double-infected A549 and Madin–Darby canine kidney cells were detected by confocal microscopy and flow cytometry.
The Effects of Low-Level Laser Therapy, 670 nm, on Epiphyseal Growth in Rats
Authors: de Andrade Adriana Regina , Meireles Anamaria , Artifon Elisangela Lourdes , Brancalhão Rose Meire Costa , Ferreira José Roberto Leonel , Bertolini Gladson Ricardo Flor
Published: April 2012

The longitudinal growth of long bones is attributed to epiphyseal growth. However, the effects of low-level laser therapy (LLLT) in such structures has still not been studied extensively in the literature. Therefore, the aim of this study was to evaluate the use of LLLT, 670 nm, at three different doses on the epiphyseal growth of the right tibia of rats. Twenty-one Wistar rats, aged four weeks, were subjected to the application of LLLT, with dosage according to the group (G4: were submitted to the application of 4 J/cm2; G8: were submitted to the application of 8 J/cm2; G16: were submitted to the application of 16 J/cm2). After completion of protocol they were kept until they were 14 weeks of age and then submitted to a radiological examination (evaluation of limb length) and euthanised. The histological analysis of the growth plates (total thickness and hypertrophic and proliferative zones) was then performed. Comparisons were made with the untreated left tibia. No differences were observed in any of the reviews (radiological and histological), when comparing the right sides (treated) to the left (untreated). It was concluded that the treatment with LLLT within the parameters used caused changes neither in areas of the epiphyseal cartilage nor in the final length of limbs.
The Use of Silver Solid Amalgam Electrodes for Voltammetric and Amperometric Determination of Nitrated Polyaromatic Compounds Used as Markers of Incomplete Combustion
Authors: Yosypchuk Oksana , Karásek Jindřich , Vyskočil Vlastimil , Barek Jiří , Pecková Karolina
Published: April 2012

Genotoxic nitrated polycyclic aromatic hydrocarbons (NPAHs) are formed during incomplete combustion processes by reaction of polycyclic aromatic hydrocarbons (PAHs) with atmospheric nitrogen oxides. 1-Nitropyrene, 2-nitrofluorene, and 3-nitrofluoranthene as the dominating substances are used as markers of NPAHs formation by these processes. In the presented study, voltammetric properties and quantification of these compounds and of 5-nitroquinoline (as a representative of environmentally important genotoxic heterocyclic compounds) have been investigated using a mercury meniscus modified silver solid amalgam electrode (m-AgSAE), which represent a nontoxic alternative to traditional mercury electrodes. Linear calibration curves over three orders of magnitude and limits of determination mostly in the 10−7 mol L−1concentration range were obtained using direct current and differential pulse voltammetry. Further, satisfactory HPLC separation of studied analytes in fifteen minutes was achieved using 0.01 mol L−1phosphate buffer, pH 7.0 : methanol (15 : 85, v/v) mobile phase, and C18reversed stationary phase. Limits of detection of around 1 · 10−5 mol L−1were achieved using amperometric detection at m-AgSAE in wall-jet arrangement for all studied analytes. Practical applicability of this technique was demonstrated on the determination of 1-nitropyrene, 2-nitrofluorene, 3-nitrofluoranthene, and 5-nitroquinoline in drinking water after their preliminary separation and preconcentration using solid phase extraction with the limits of detection around 1 · 10−6 mol L−1.
Fluorescence-Based Rapid Detection of Microbiological Contaminants in Water Samples
Authors: Meder Hervé , Baumstummler Anne , Chollet Renaud , Barrier Sophie , Kukuczka Monika , Olivieri Frédéric , Welterlin Esther , Beguin Vincent , Ribault Sébastien
Published: April 2012

Microbiological contamination of process waters is a current issue for pharmaceutical industries. Traditional methods require several days to obtain results; therefore, rapid microbiological methods are widely requested to shorten time-to-result. Milliflex Quantum was developed for the rapid detection and enumeration of microorganisms in filterable samples. It combines membrane filtration to universal fluorescent staining of viable microorganisms. This new alternative method was validated using European and United States Pharmacopeia definitions, with sterile water and/or sterile water artificially contaminated with microorganisms. The Milliflex Quantum method was demonstrated to be reliable, robust, specific, accurate, and linear over the whole range of assays following these guidelines. The Milliflex Quantum system was challenged to detect natural contaminants in different types of pharmaceutical purified process waters. Milliflex Quantum was demonstrated to detect accurately contaminants 3- to 7-fold faster than traditional membrane filtration method. The staining procedure is nondestructive allowing downstream identification following a positive result. The Milliflex Quantum offers a fast, sensitive, and robust alternative to the compendial membrane filtration method.
PTEN Gene: A Model for Genetic Diseases in Dermatology
Authors: Romano Corrado , Schepis Carmelo
Published: April 2012

PTEN gene is considered one of the most mutated tumor suppressor genes in human cancer, and it’s likely to become the first one in the near future. Since 1997, its involvement in tumor suppression has smoothly increased, up to the current importance. Germline mutations of PTEN cause the PTEN hamartoma tumor syndrome (PHTS), which include the past-called Cowden, Bannayan-Riley-Ruvalcaba, Proteus, Proteus-like, and Lhermitte-Duclos syndromes. Somatic mutations of PTEN have been observed in glioblastoma, prostate cancer, and brest cancer cell lines, quoting only the first tissues where the involvement has been proven. The negative regulation of cell interactions with the extracellular matrix could be the way PTEN phosphatase acts as a tumor suppressor. PTEN gene plays an essential role in human development. A recent model sees PTEN function as a stepwise gradation, which can be impaired not only by heterozygous mutations and homozygous losses, but also by other molecular mechanisms, such as transcriptional regression, epigenetic silencing, regulation by microRNAs, posttranslational modification, and aberrant localization. The involvement of PTEN function in melanoma and multistage skin carcinogenesis, with its implication in cancer treatment, and the role of front office in diagnosing PHTS are the main reasons why the dermatologist should know about PTEN.
Reproductive Ecology of Male and Female Strobili and Mating System in Two Different Populations ofPinus roxburghii
Authors: Sharma Chandra Mohan , Khanduri Vinod Prasad , Ghildiyal Sunil Kumar
Published: April 2012

We studied several flowering traits, namely, male-female cone phenology, male-female cone production per tree, mating system, sex ratio, air-borne pollen grains and pollen migration, over four successive years in two different natural populations ofP. roxburghiifrom Garhwal Himalaya, India. Assessment of each trait mentioned except pollen dispersion was done by selecting five representative trees randomly in each population. The pollen migration was studied on naturally isolated source trees. The pollen trapping was done in all directions up to 2.5 km. The average reproductive period inP. roxburghiiwas 36 days with 3–5 days protandry. There were significant year and population effects for male and female cone output and pollen grains production per tree. In mass production year (1999), an average production of pollen cone per tree was estimated as42.44±8.32×103at lower altitude and28.1±0.89×103at higher altitude. The controlled pollination results in high level of outcrossing with 90% seed setting. We conclude that the high male-female ratio and tremendous pollen production capacity inP. roxburghiiindicate high male competition among trees within populations. The isolation strip of 600 m is considered minimal for the management of seed orchard.
Changes in Cardiac Tone Regulation with Fatigue after Supra-Maximal Running Exercise
Authors: Leprêtre Pierre-Marie , Lopes Philippe , Thomas Claire , Hanon Christine
Published: April 2012

To investigate the effects of fatigue and metabolite accumulation on the postexercicse parasympathetic reactivation, 11 long-sprint runners performed on an outdoor track an exhaustive 400 m long sprint event and a 300 m with the same 400 m pacing strategy. Time constant of heart rate recovery (HRR), time (RMSSD), and frequency (HF, and LF) varying vagal-related heart rate variability indexes were assessed during the 7 min period immediately following exercise. Biochemical parameters (blood lactate, pH, PO2, PCO2, SaO2, and HCO3−) were measured at 1, 4 and 7 min after exercise. Time to perform 300 m was not significantly different between both running trials. HHR measured after the 400 m running exercise was longer compared to 300 m running bouts ( versus  s, ). Absolute power density in the LF and HF bands was also lower after 400 m compared to the 300 m trial (). No correlation was found between biochemical and cardiac recovery responses except for the PO2values which were significantly correlated with HF levels measured 4 min after both bouts. Thus, it appears that fatigue rather than metabolic stresses occurring during a supramaximal exercise could explain the delayed postexercise parasympathetic reactivation in longer sprint runs.
Social Networking Sites and Educational Adaptation in Higher Education: A Case Study of Chinese International Students in New Zealand
Authors: Cao Ling , Zhang Tingting
Published: April 2012

This study aims to find out the relationship between the use of SNSs and educational adaptation process of Chinese international students (from China) in New Zealand. Based on interview data, this paper addressed how Chinese international students use SNSs (RenRen, Facebook, etc.) to expand and manage their online social networks to help their adaptation to new educational environment. As a case study of Chinese international students in New Zealand and from the narrative of students, we examined the relationship among educational difficulties, life satisfaction, and the use of SNSs. This study would help in further understanding how and why SNSs can be adopted in higher education to support effective overseas learning experiences.
Transcaruncular Medial Wall Orbital Decompression: An Effective Approach for Patients with Unilateral Graves Ophthalmopathy
Authors: Hill Robert H. , Czyz Craig N. , Bersani Thomas A.
Published: April 2012

Purpose. To evaluate the reduction in proptosis, incidence of postoperative diplopia, and postoperative globe symmetry after transcaruncular medial wall decompression in patients with unilateral Graves ophthalmopathy.Methods. Retrospective review of 16 consecutive patients who underwent unilateral transcaruncular medial wall orbital decompression from 1995 to 2007. The diagnosis of Graves ophthalmopathy was based on history and clinical findings including proptosis, lagophthalmos, lid retraction, motility restriction, and systemic thyroid dysfunction.Results. The mean reduction in proptosis was 2.3 mm. The mean difference in exophthalmometry preoperatively between the two eyes in each patient was 3.1 mm whereas postoperatively the mean difference was 1.1 mm (P=0.0002). Eleven of 16 patients (69%) had 1 mm or less of asymmetry postoperatively. There was no statistically significant difference in the incidence of diplopia pre- and postoperatively (P=1.0).Conclusions. Medial wall orbital decompression is a safe and practical surgical approach for patients with unilateral Graves orbitopathy. The procedure carries a low risk of morbidity and yields anatomic retrusion of the globe that is comparable to other more invasive methods and may yield more symmetric postoperative results.
Antioxidant Action of Mangrove Polyphenols against Gastric Damage Induced by Absolute Ethanol and Ischemia-Reperfusion in the Rat
Authors: de-Faria Felipe Meira , Almeida Ana Cristina Alves , Luiz-Ferreira Anderson , Takayama Christiane , Dunder Ricardo José , da Silva Marcelo Aparecido , Salvador Marcos José , Abdelnur Patrícia Verardi , Eberlin Marcos Nogueira , Vilegas Wagner , Toma Walber , Souza-Brito Alba Regina Monteiro
Published: April 2012

Rhizophora mangle, the red mangrove, has long been known as a traditional medicine. Its bark has been used as astringent, antiseptic, hemostatic, with antifungic and antiulcerogenic properties. In this paper, we aimed to evaluate the antioxidant properties of a buthanolic fraction of theR. manglebark extract (RM) against experimental gastric ulcer in rats. Unib-Wh rats received pretreatment ofR. mangleafter the induction of gastric injury with absolute ethanol and ischemia-reperfusion. Gastric tissues from both methods were prepared to the enzymatic assays, the levels of sulfhydril compounds (GSH), lipid peroxides (LPO), and the activities of glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD) and myeloperoxidase (MPO) were measured. The RM protected the gastric mucosa in both methods used, ethanol-induced gastric ulcer and ischemia-reperfusion, probably, by modulating the activities of the enzymes SOD, GPx, and GR and increasing or maintaining the levels of GSH; in adittion, LPO levels were reduced. The results suggest that the RM antioxidant activity leads to tissue protection; thus one of the antiulcer mechanisms present on the pharmacological effects ofR. mangleis the antioxidant property.
The Clinical COPD Questionnaire Correlated with BODE Index-A Cross-Sectional Study
Authors: Liu Shih-Feng , Tseng Ching-Wan , Tu Mei-Lien , Wang Chin-Chou , Tseng Chia-Cheng , Chin Chien-Hung , Lin Meng-Chih , Liu Jien-Wei
Published: April 2012

The Global initiative for Chronic Obstructive Lung Disease (GOLD) staging has widely used in the stratification of the severity of COPD, while BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index was proven superior to FEV1 in predicting mortality, exacerbation and disease severity in patients with COPD. Clinical COPD Questionnaire (CCQ), a questionnaire with ten items categorized into three domains (symptoms, functional state and mental state) was developed to measure health status of COPD patients. However, little is known about the relationship between CCQ score and BODE index. We performed a prospective study with the inclusion of 89 patients who were clinically stable after a 6-week-therapy for COPD symptoms comparing their health status assessed by CCQ, BODE index and GOLD staging. We found that the total CCQ score was correlated with BODE score (P<0.001) and GOLD staging (P<0.001); of three CCQ domains, the functional status correlated the most with BODE index (rS=0.670) and GOLD staging (rS=0.531), followed by symptoms (rS=0.482;rS=0.346, respectively), and mental status (rS=0.340;rS=0.236, respectively). Our data suggest that CCQ is a reliable and convenient alternative tool to evaluate the severity of COPD.
Salicylic Acid Attenuates Gentamicin-Induced Nephrotoxicity in Rats
Authors: Randjelovic Pavle , Veljkovic Slavimir , Stojiljkovic Nenad , Jankovic-Velickovic Ljubinka , Sokolovic Dusan , Stoiljkovic Milan , Ilic Ivan
Published: April 2012

Gentamicin (GM) is a widely used antibiotic against serious and life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of salicylic acid (SA) in gentamicin-induced nephrotoxicity in rats. Quantitative evaluation of gentamicin-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of SA coadministration with gentamicin. Gentamicin was observed to cause a severe nephrotoxicity which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde (MDA) levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous SA administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by SA pretreatment. The results from our study indicate that SA supplement attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation in gentamicin-treated rats.
Antibiotic Resistance ofSalmonella entericaSerovar Typhi in Kolkata, India, andIn VitroExperiments on Effect of Combined Chemotherapy
Authors: Mandal Shyamapada , DebMandal Manisha , Pal Nishith Kumar
Published: April 2012

This communication states the changing patterns ofSalmonella entericaserovar Typhi (S.Typhi) isolates causing enteric fever in and around Kolkata, India. Among the isolates resistance to ampicillin (A), chloramphenicol (C), cotrimoxazole (Co) and tetracycline (T) were plasmid mediated; the plasmid was unstable inS.Typhi, and the other enteric bacteria likeEscherichia coli, Klebsiella pneumoniae and Proteus vulgaris were found to be the potential source of dissemination of such plasmids intoS.Typhi. The infection with suchS.Typhi strains were successfully treated with ciprofloxacin (Cp: MICs 0.0075–0.075 μg mL−1) and/or ofloxacin (Ofx: MICs 0.0125–0.075 μg mL−1), but in the later course, theS.Typhi strains, showing resistance to nalidixic acid, developed low level of resistance to Cp and Ofx, causing the treatment failure. Thus, the treatment regimen was shifted to the third generation cephalosporins like ceftriaxone (Ct) and cefotaxime (Cf). Keeping in mind the anticipation of development of resistance to Ct/Cf, we prepared the treatment regimen for MDR enteric fever, based on the double-drug synergy tests in vitro; Cp-gentamycin (FICI 0.121–0.216) and Cp-trimethoprim (FICI 0.14–0.483) combinations were found effective againstS.Typhi isolates having decreased sensitivity to cp (MICs: 0.5–1.25 μg mL−1).
Occurrence of Morphological and Anatomical Adaptive Traits in Young and Adult Plants of the Rare Mediterranean Cliff SpeciesPrimula palinuriPetagna
Authors: De Micco Veronica , Aronne Giovanna
Published: April 2012

Cliffs worldwide are known to be reservoirs of relict biodiversity. Despite the presence of harsh abiotic conditions, large endemic floras live in such environments.Primula palinuriPetagna is a rare endemic plant species, surviving on cliff sites along a few kilometres of the Tyrrhenian coast in southern Italy. This species is declared at risk of extinction due to human impact on the coastal areas in question. Population surveys have shown that most of the plants are old individuals, while seedlings and plants at early stages of development are rare. We followed the growth ofP. palinuriplants from seed germination to the adult phase and analysed the morphoanatomical traits of plants at all stages of development. Our results showed that the pressure of cliff environmental factors has been selected for seasonal habitus and structural adaptive traits in this species. The main morphoanatomical modifications are suberized cell layers and accumulation of phenolic compounds in cell structures. These features are strictly related to regulation of water uptake and storage as well as defence from predation. However, we found them well established only in adult plants and not in juvenile individuals. These findings contribute to explain the rare recruitment of the present relict populations, identifying some of the biological traits which result in species vulnerability.
Analysis of Quality of Nuchal Translucency Measurements: Its Role in Prenatal Diagnosis
Authors: Gabriel Carmen Comas , Echevarria M. , Rodríguez I. , Serra B.
Published: April 2012

Objective. Quantitative analysis of the quality of nuchal translucency (NT) measurements.Methods. First-trimester combined screening for Down syndrome was performed to all pregnant women attended in our Department from October 2003 to November 2009. NT was measured according to the Fetal Medicine Foundation (FMF) criteria by 20 trained obstetricians. The performance of NT measurements was retrospectively analyzed with regard to several quality control standards. Accuracy according to experience, professional profile, crown rump length (CRL) values, and FMF certification was statistically tested.Results. A total of 14978 NT measurements were assessed. (1) The mean operator-specific median NT-MoM values was 0,98. (2) Mean percentage of cases >95th and <5th centiles were 5,0% and 4,2%, respectively. (3) Logarithmic mean and SD of the NT MoM values were 0,00 and 0,13, respectively. (4) The DR for trisomy 21 at screening time was 90,7% for a FPR of 6,7% for standard screening strategy. (5) According to Cumulative SUM (CUSUM) figures, the performance was more acceptable in FMF-certified operators.Conclusion. Overall, quality standards show optimal NT measurements in our unit. Operator experience, a dedicated profile to fetal medicine, CRL over 60 mm, and FMF certification have a significant positive impact on the quality standards.
Ultrashort and progressive 4sU-tagging reveals key characteristics of RNA processing at nucleotide resolution
Authors: Windhager Lukas , Bonfert Thomas , Burger Kaspar , Ruzsics Zsolt , Krebs Stefan , Kaufmann Stefanie , Malterer Georg , L'Hernault Anne , Schilhabel Markus , Schreiber Stefan , Rosenstiel Philip , Zimmer Ralf , Eick Dirk , Friedel Caroline C. , Dölken Lars
Published: April 2012

RNA synthesis and decay rates determine the steady-state levels of cellular RNAs. Metabolic tagging of newly transcribed RNA by 4-thiouridine (4sU) can reveal the relative contributions of RNA synthesis and decay rates. The kinetics of RNA processing, however, had so far remained unresolved. Here, we show that ultrashort 4sU-tagging not only provides snapshot pictures of eukaryotic gene expression but, when combined with progressive 4sU-tagging and RNA-seq, reveals global RNA processing kinetics at nucleotide resolution. Using this method, we identified classes of rapidly and slowly spliced/degraded introns. Interestingly, each class of splicing kinetics was characterized by a distinct association with intron length, gene length, and splice site strength. For a large group of introns, we also observed long lasting retention in the primary transcript, but efficient secondary splicing or degradation at later time points. Finally, we show that processing of most, but not all small nucleolar (sno)RNA-containing introns is remarkably inefficient with the majority of introns being spliced and degraded rather than processed into mature snoRNAs. In summary, our study yields unparalleled insights into the kinetics of RNA processing and provides the tools to study molecular mechanisms of RNA processing and their contribution to the regulation of gene expression.
Exploring the DNA-recognition potential of homeodomains
Authors: Chu Stephanie W. , Noyes Marcus B. , Christensen Ryan G. , Pierce Brian G. , Zhu Lihua J. , Weng Zhiping , Stormo Gary D. , Wolfe Scot A.
Published: April 2012

The recognition potential of most families of DNA-binding domains (DBDs) remains relatively unexplored. Homeodomains (HDs), like many other families of DBDs, display limited diversity in their preferred recognition sequences. To explore the recognition potential of HDs, we utilized a bacterial selection system to isolate HD variants, from a randomized library, that are compatible with each of the 64 possible 3′ triplet sites (i.e., TAANNN). The majority of these selections yielded sets of HDs with overrepresented residues at specific recognition positions, implying the selection of specific binders. The DNA-binding specificity of 151 representative HD variants was subsequently characterized, identifying HDs that preferentially recognize 44 of these target sites. Many of these variants contain novel combinations of specificity determinants that are uncommon or absent in extant HDs. These novel determinants, when grafted into different HD backbones, produce a corresponding alteration in specificity. This information was used to create more explicit HD recognition models, which can inform the prediction of transcriptional regulatory networks for extant HDs or the engineering of HDs with novel DNA-recognition potential. The diversity of recovered HD recognition sequences raises important questions about the fitness barrier that restricts the evolution of alternate recognition modalities in natural systems.
First‐line sunitinib plus FOLFIRI in Japanese patients with unresectable/metastatic colorectal cancer: A phase II study
Authors: Tsuji Yasushi , Satoh Taroh , Tsuji Akihito , Muro Kei , Yoshida Motoki , Nishina Tomohiro , Nagase Michitaka , Komatsu Yoshito , Kato Takeshi , Miyata Yoshinori , Mizutani Naoko , Hashigaki Satoshi , Lechuga Maria Jose , Denda Tadamichi
Published: April 2012

This phase II, open‐label, single‐arm study investigated sunitinib + FOLFIRI in Japanese patients with treatment‐naïve unresectable/metastatic colorectal cancer. Patients received i.v. FOLFIRI (levo‐leucovorin 200 mg/m2 + irinotecan 180 mg/m2, followed by 5‐fluorouracil 400 mg/m2 bolus then 2400 mg/m2 46‐h infusion) every 2 weeks, and oral sunitinib 37.5 mg/day on Schedule 4/2 (4 weeks on, 2 weeks off), until disease progression or treatment withdrawal. Progression‐free survival (PFS) was the primary endpoint, with a target median of 10.8 months (35% improvement over FOLFIRI alone). Seventy‐one patients started a median of 3 (range 1–11) sunitinib cycles (median relative dose intensity, <60%). The median PFS was 6.7 months (95% confidence interval, 4.7–9.2) by independent review, 7.2 months (95% confidence interval, 5.4–9.5) by investigator assessment. Objective response rate (complete responses + partial responses) was 36.6% (independent review) and 42.3% (investigator assessment). Clinical benefit rate (complete responses + partial responses + stable disease) was 83.1% (independent review) and 88.7% (investigator assessment). Common all‐causality, any‐grade, adverse events were: neutropenia and leukopenia (both 97.2%); thrombocytopenia (84.5%); diarrhea and nausea (both 78.9%); decreased appetite (74.6%); and fatigue (66.2%). Neutropenia (96%) was the most frequent grade 3/4 adverse event. This study was closed early due to findings from a concurrent phase III study of sunitinib + FOLFIRI in non‐Japanese patients with metastatic colorectal cancer. In conclusion, the median PFS for sunitinib + FOLFIRI in Japanese patients was shorter than the 10.8 month target, indicating that sunitinib did not add to the antitumor activity of FOLFIRI. This study was registered with www.ClinicalTrials.gov (NCT00668863). (Cancer Sci, doi: 10.1111/j.1349‐7006.2012.02320.x, 2012)
Idiopathic noncirrhotic portal hypertension is associated with poor survival: results of a long‐term cohort study
Authors: Schouten J. N. L. , Nevens F. , Hansen B. , Laleman W. , van den Born M. , Komuta M. , Roskams T. , Verheij J. , Janssen H. L. A.
Published: April 2012

Background

Idiopathic noncirrhotic portal hypertension (INCPH) is a rare disease in the Western world. As a result, little is known about the clinical characteristics and outcome of these patients. Survival in these patients is considered to be similar to that of the general population.

Aim

To investigate the clinical manifestations, pathophysiology, outcome and determinants of survival in Western INCPH patients.

Methods

Multicentre cohort study of INCPH patients.

Results

A total of 62 patients were followed for a median time of 90 months (range 24–310). Initial manifestations leading to the diagnosis of INCPH were related to portal hypertension in 82% of the patients. Histological signs of portal blood supply disturbances were present in nearly all patients. During follow‐up, 12 of 62 patients developed liver decompensation, of which four were considered for liver transplantation. One patient died in the context of variceal bleeding. Hepatocellular carcinoma was not observed during follow‐up. A total of 23 patients died during follow‐up, only four of them due to liver related mortality. The Kaplan–Meier estimates for overall survival were 100% (95% CI 95–100%), 78% (95% CI 67–89%) and 56% (95% CI 40–72%) at 1, 5 and 10 years respectively. Survival for INCPH was significantly decreased (P < 0.001) compared to survival of the general population. Ascites was an independent predictor of poor outcome.

Conclusions

In comparison to the general population, survival in INCPH patients is poor. Mortality is related to associated disorders and medical conditions occurring at older age. Patients rarely die due to liver related complications. Patients with ascites have a poor prognosis.
Unconjugated hyperbilirubinemia is inversely associated with non‐alcoholic steatohepatitis (NASH)
Authors: Hjelkrem M. , Morales A. , Williams C. D. , Harrison S. A.
Published: April 2012

Background

It has been recognised that unconjugated bilirubin contains hepatic anti‐fibrogenic and anti‐inflammatory properties and is a potent physiological antioxidant cytoprotectant. We believe that unconjugated hyperbilirubinemia may protect against development of non‐alcoholic steatohepatitis (NASH).

Aim

This study was conducted to assess the association of serum unconjugated bilirubin levels and histological liver damage in non‐alcoholic fatty liver disease (NAFLD).

Methods

This was a retrospective analysis involving adult patients from a tertiary medical centre undergoing liver biopsy to evaluate suspected NAFLD or NASH and a control group without NAFLD based on normal liver ultrasound, labs and history. Identification of unconjugated hyperbilirubinemia was based on the presence of predominantly unconjugated bilirubin ≥1.0 mg/dL (17.1 μmol/L) while fasting, in the absence of haemolytic disease or other hepatic function alteration.

Results

Six‐hundred and forty‐one patients were included. Unconjugated hyperbilirubinemia was inversely associated with NASH (OR 16.1, 95% CI 3.7–70.8 P < 0.001). Of the patients without NAFLD (133 patients), 13 (9.8%) had unconjugated hyperbilirubinemia (range 1.0–1.8, mean 1.4). Of the patients with NAFLD without NASH (285 patients), 32 (11.2%) had unconjugated hyperbilirubinemia (range 1.0–3.0, mean 1.4). Of the patients with NASH (223 patients), three (1.3%) had unconjugated hyperbilirubinemia (1.0, 1.1, 1.4).

Conclusions

Unconjugated hyperbilirubinemia is inversely associated with the histopathological severity of liver damage in non‐alcoholic fatty liver disease.
Quality of life and control of allergic rhinitis in patients from regions beyond western Europe and the United States
Authors: Maspero J. , Lee B. W. , Katelaris C. H. , Potter P. C. , Cingi C. , Lopatin A. , Saffer M. , Nadeau G. , Walters R. D.
Published: April 2012

There is comparatively little information on health‐related quality of life (HRQoL) in subjects with allergic rhinitis (AR) or allergic rhinoconjunctivitis (AR/C) in countries beyond western Europe and North America. The primary aim of this investigation was therefore to review and assess the information in the public domain on HRQoL in AR/C patients from diverse regions of the world, represented by different countries, including Argentina, Australia, Brazil, Russia, Singapore, South Africa and Turkey. Second, in view of the absence of a standardized definition for ‘AR control’, the review aimed to determine whether a working definition of AR/C can be inferred from validated tests or other instruments documented to date. Despite the comparatively low number of studies, this review demonstrated that overall the symptoms of AR/C impair the HRQoL of patients in these regions by adversely impacting sleep, daily activities, physical and mental status and social functioning, similar to that demonstrated in much larger numbers of studies of AR/C patients in Europe and the United States. Furthermore, the findings of the review suggest that ‘overall’ control of the disease should encompass reduction of nasal and ocular symptoms, as well as improvements in HRQoL, comorbid conditions and cognition. Although some instruments are currently available for measuring control of AR, none are capable of assessing all these aspects, emphasizing the need to develop appropriate new instruments.
Dynamics of soil carbon to nitrogen ratio changes under long‐term fertilizer addition in wheat‐corn double cropping systems of China
Authors: Cong R. H. , Wang X. J. , Xu M. G. , Zhang W. J. , Xie L. J. , Yang X. Y. , Huang S. M. , Wang B. R.
Published: April 2012

Soil carbon to nitrogen (C:N) ratio is one of the important properties of terrestrial ecosystems. Here, we report a study of soil C:N ratio dynamics in wheat‐corn double cropping systems based on four long‐term experimental sites in China: three in the temperate zone and one in the sub‐tropical zone. We evaluate effects of long‐term fertilizer input on soil organic carbon (SOC) and total nitrogen (TN) by comparing three treatments: no added fertilizer (the control), added nitrogen‐phosphorus‐potassium chemical fertilizers (NPK), and chemical fertilizers combined with manure (NPKM). Our study shows that SOC and TN had different responses to the treatments. There was an increasing trend in SOC, even without fertilizer. However, applying inorganic fertilizers only (NPK) did not maintain TN contents at some sites. The NPKM treatment resulted in a large increase in both SOC (35–147%) and TN (33 to 10%) contents, relative to the initial values. The soil C:N ratio showed a significant increase over time at the sub‐tropical site but little change at the three temperate sites. Our analysis showed similar C:N ratios (37–38) in gross input of organic materials under the NPK treatments. However, the estimated C:N ratio during decomposition was much smaller at the sub‐tropical site (23.7) than at the three temperate sites (44.0–48.2) under the NPK treatments, which may explain the increased soil C:N ratio at the sub‐tropical site. Thus, we conclude that variations in soil C:N ratio are not caused by organic matter inputs but by decomposition in the wheat‐corn double cropping systems.
Rate of desorption of eight heavy metals from goethite and its implications for understanding the pathways for penetration
Authors: Barrow N. J. , Brümmer G. W. , Fischer L.
Published: April 2012

We compared rates of desorption of heavy metals from goethite, an important soil constituent, in order to understand the mechanisms of sorption and desorption better. Samples of goethite were reacted with salt solutions of heavy metals for 2 hours or for 8 weeks. The metals were Cr, Mn, Co, Ni, Cu, Zn, Cd and Pb. Desorption was then induced by successive treatments with 0.7 m HNO3 for up to 360 hours followed by complete dissolution of the goethite particles. After brief sorption (2 hours), a large proportion of the sorbed metals was desorbed by brief treatment (15 minutes) with HNO3. This suggests that the metals were mainly sorbed on, or close to, external goethite surfaces. After longer sorption (8 weeks), even 360 hours of extraction with 0.7 m HNO3 did not recover all of the sorbed metals. Complete dissolution of the goethite particles was necessary. This suggests that the eight heavy metals had penetrated the goethite particles deeply. When desorption was summarized using a pragmatic equation, it was only for brief sorption followed by brief desorption that indices of the rate of desorption were well correlated with measures of the rate of sorption as obtained in an earlier work. When desorption was described with a mechanistic model, observed desorption was often faster than predicted and the discrepancy was greatest with the shorter periods of desorption. The discrepancy was marked for Ni, Cr and Co. We think this was because large portions of these metals were incorporated into the goethite structure by lattice diffusion and were therefore held close to the surface. When the acid dissolved some of the goethite these metals were released. For long‐term desorption and for most metals, the ratio of observed to predicted desorption decreased with increasing ionic radius. We think that this reflects a changing balance between lattice and pore diffusion, with lattice diffusion more important for metals with radii near that of Fe (Cr, Co, Ni), and pore diffusion more important for the larger cations of Cd and Pb. Manganese was an exception. Desorption was at first faster than predicted but then declined to be close to predicted values. This suggests that Mn mostly penetrated more deeply by pore diffusion.
Is on‐demand treatment effective in patients with severe haemophilia?
Authors: AZNAR J. A. , MARCO A. , JIMÉNEZ‐YUSTE V. , FERNÁNDEZ‐FONTECHA E. , PÉREZ R. , SOTO I. , PARRA R. , MORENO M. , MINGOT M. E. , MORET A. ,   ON BEHALF OF THE SPANISH HAEMOPHILIA EPIDEMIOLOGICAL STUDY WORKING GROUP
Published: April 2012

Summary.  On‐demand therapy enables stopping haemorrhages rapidly, reducing joint pain and restoring joint mobility, but does not prevent the beginning and subsequent development of haemophilic arthropathy. The main objective of this study was to identify the clinical and orthopaedic status of severe haemophilic patients with bleeding phenotype receiving on‐demand treatment in Spain. We conducted an epidemiological, observational, retrospective study, recruiting 167 patients from 36 centres (92% of them with haemophilia A), median age at enrolment of 35 years. Forty per cent of the patients received a combination of on‐demand and short‐term prophylaxis regimen; the rest was under on‐demand treatment. One hundred and forty‐five patients (87%) reported at least one bleeding episode and 22 (13%) of the biologically severe patients had no bleeding phenotype. Seventy‐one per cent of the studied population presented established haemophilic arthropathy, reaching 80% if we exclude patients without bleeding phenotype. Forty‐three per cent of these patients had one or two joints affected, 28% of them had three or four affected joints, 20% reported five or six affected joints and 9% more than six injured joints. An increase in established haemophilic arthropathy with age was observed. Forty‐six patients underwent orthopaedic surgery at least once. These data show that on‐demand therapy is not effective in preventing the development of haemophilic arthropathy in severe haemophilic population with bleeding phenotype. Therefore, we suggest that the optimal treatment in these patients should be based on prophylaxis. We recommend analysing the reasons for ending prophylaxis, in case its reinstatement should be necessary.
Specific histological abnormalities are more likely in biopsies of endoscopically normal large bowel after the age of 60 years
Authors: O’Mahony Orla H , Burgoyne Margaret , Going James J
Published: April 2012

O’Mahony O H, Burgoyne M & Going J J  (2012) Histopathology

Specific histological abnormalities are more likely in biopsies of endoscopically normal large bowel after the age of 60 years

Aims:  Colonic and rectal biopsies, often taken from an endoscopically normal large bowel, form a significant proportion of the histopathology workload. The aim of this study was to determine diagnostic yield from mucosal biopsies in patients with normal colonoscopy or sigmoidoscopy, and whether or not diarrhoea is predictive of abnormal histology.

Methods and results:  A retrospective analysis of pathology requests, endoscopy and pathology reports taken during 1 year was undertaken in a tertiary care hospital for all biopsies from endoscopically normal ileal, colonic and rectal mucosa. Of 626 patients fulfilling inclusion criteria, 602 had at least one colonic or rectal biopsy. Colorectal histology was abnormal in 65 (14.5%) of 447 patients with diarrhoea, while of 155 patients without diarrhoea, histology was abnormal in 17 (11%; P = 0.41). Patients older than 60 years had a markedly increased likelihood of a specific histological abnormality [odds ratio 2.76 (1.30–5.79); P = 0.0045]. Diagnoses included microscopic colitis, distorted mucosal architecture consistent with inflammatory bowel disease, ischaemia, polyps, mucosal prolapse and schistosomiasis.

Conclusions:  Biopsy of an endoscopically normal large bowel, and of the normal terminal ileum in isolation, yields little abnormal histology. Diarrhoea per se does not identify patients at higher risk of abnormal histology. Increased age, however, does, and mucosal biopsy in the endoscopically normal colon and rectum may be more cost‐effective in patients aged more than 60 years.
Differences in loosely bound fluoride formation and anticaries effect of resin‐based fluoride varnishes
Authors: MAAS JORGE R. S. , JUNIOR ITALO M. FARACO , LODI CAROLINA S. , DELBEM ALBERTO C. B.
Published: April 2012

International Journal of Paediatric Dentistry 2013; 23: 166–172

Objective.  Our in vitro study evaluated calcium fluoride formation in enamel and the anticaries effect of seven resin‐based varnishes under cariogenic challenge.

Methods.  Enamel blocks were subjected to pH cycling. The experimental groups received fluoride varnish application, the positive control received topical fluoride gel treatment, and the negative control did not receive any treatment. The pH cycling surface hardness (SH1) and integrated loss of subsurface hardness (ΔKHN) were then determined. We measured the amount of fluoride released into the demineralizing and remineralizing (DE–RE) solutions used in pH cycling. The fluoride concentration in the enamel was determined 24 h after application of the products as loosely bound fluoride and firmly bound fluoride.

Results.  Higher deposits of loosely bound fluoride were observed for Duofluorid, followed by Biophat. For Duraphat, Bifluorid, Duraflur, and Duofluorid, no difference was observed in the SH1 and ΔKHN values, with the lowest mineral loss compared to the other groups. The Bifluorid and Duofluorid groups released high fluoride amounts into the DE–RE, and statistically significant difference was noted between them.

Conclusions.  The anticaries effect showed no correlation with higher deposited fluoride amounts, resin type, or fluoride source.
Wild pollination services to California almond rely on semi‐natural habitat
Authors: Klein Alexandra‐Maria , Brittain Claire , Hendrix Stephen D. , Thorp Robbin , Williams Neal , Kremen Claire
Published: April 2012

1. Global declines in honeybees have led to concerns about negative impacts on food production because of low levels of pollination. This is exemplified in California where the demand for honeybees Apis mellifera to pollinate almond Prunus dulcis is increasing, but problems with honeybee health suggest it may not be sustainable to rely solely on the pollination service of a single species.

2. We investigated the effect of the quantity of surrounding natural habitat, organic management and strips of semi‐natural vegetation on flower visitation frequency of wild and managed pollinators and fruit set in 23 California almond orchards (15 conventional, 8 organic). Five conventional and four organic orchards were surrounded by a low percentage (<5%) of natural or semi‐natural habitat in a 1‐km radius and another five conventional and four organic orchards were surrounded by a high percentage of these habitats (>30%). A further five conventional orchards with a low percentage of surrounding natural habitat had an adjacent strip of semi‐natural vegetation and were included in the study to represent a realistic option for orchard management in intensive agricultural landscapes.

3. Wild bee species visited almond flowers but only in orchards with adjacent semi‐natural habitat or vegetation strips. Organic management increased the flower visitation frequencies of hover flies and wild bees. The presence of a strip of semi‐natural vegetation in orchards with a low percentage of surrounding natural habitat increased the number of species and the flower visitation frequency by wild pollinators but only at orchard edges and not to the degree seen when natural habitat was abundant.

4. Wild bee species richness and flower visitation frequency, but not honeybee frequency, were related to fruit set. Fruit set increased with increasing percentage of natural habitat surrounding the orchards. Organic farming or the presence of a vegetation strip did not increase fruit set.

5. Synthesis and applications. The restoration of high quality habitat strips along the edges of crop fields in highly intensified agricultural landscapes should be encouraged and monitored to conserve pollinators and to determine whether benefits for agriculture can be realized. Although honeybees are the main and most important pollinating insects for many plants, wild pollinators may be necessary to ensure high fruit set. Organic farming alone will not sustain wild pollination services for almond in California.