bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computer-Based Analysis of the Optokinetic Response in Zebrafish Larvae
Authors: Hodel Corinne , Neuhauss Stephan C. F. 
Published: March 2008

INTRODUCTIONLarge movements in the visual field trigger stereotypic eye movements in vertebrates. This optokinetic response (OKR) is robust in zebrafish (Danio rerio) larvae older than 4 days post-fertilization (dpf), and is hence ideally suited for use in the evaluation of visual performance after genetic manipulations. This protocol describes a simple method by which a computer-generated visual stimulus is projected onto a screen and watched by immobilized larvae. The resulting eye movements are recorded and evaluated automatically, using a digital video camera and appropriate computer software. Depending on the sophistication of the software used, the evaluation can be performed in real time during the recording session, or by analyzing the recorded movie files off-line.
Phenotypic Analysis of Arabidopsis Mutants: Hypocotyl Length
Authors: Borevitz Justin , Neff Michael 
Published: March 2008

INTRODUCTIONHypocotyl elongation of young seedlings is an important response affected by both endogenous developmental programs and exogenous signals, such as light quality and quantity. When a seed germinates in the dark (as it might if it were buried in soil), the hypocotyl extends and the cotyledons remain folded under a protective hook. When the seedling reaches the light, the rate of hypocotyl elongation is inhibited, and vegetative development is initiated. This protocol describes the measurement of hypocotyl lengths in freshly germinated seedlings.
Strategies for Overcoming PCR Inhibition
Authors: Rådström Peter , Löfström Charlotta , Lövenklev Maria , Knutsson Rickard , Wolffs Petra 
Published: March 2008

INTRODUCTIONThe use of conventional and real-time PCR is to some extent restricted by the presence of PCR inhibitors. This is particularly so when the techniques are applied directly to complex biological samples such as clinical, environmental, or food samples for the detection of microorganisms. PCR inhibitors can originate from the sample itself, or as a result of the method used to collect or otherwise prepare the sample. Either way, inhibitors can dramatically reduce the sensitivity and amplification efficiency of PCR. This article discusses methods of reducing inhibition and designing reliable and sensitive conventional and real-time PCR experiments.
Genetic Analysis of Arabidopsis Mutants
Authors: Weigel Detlef , Glazebrook Jane 
Published: March 2008

INTRODUCTIONThe inheritance of mutant phenotypes in Arabidopsis thaliana is most often analyzed in the progeny resulting from crosses between different parents. This article describes genetic strategies for the analysis of mutants. Newly identified mutations can be examined initially using segregation analysis, followed by backcrossing and cosegregation for removal of extraneous mutations and assessment of pleiotropy. Confirmation that a phenotype of interest results from a given mutation can be achieved via complementation testing, which is also used to determine allelism of recessive mutations. The construction of double mutants is useful in the study of signal transduction and metabolic pathways. Considerations for the use of double homozygotes and their identification in the F2 and F3 generations are described at the end of this article.
Safety, tolerability and pharmacokinetics of udenafil, a novel PDE‐5 inhibitor, in healthy young Korean subjects
Authors: Kim Bo‐Hyung , Lim Hyeong‐Seok , Chung Jae‐Yong , Kim Jung‐Ryul , Lim Kyoung Soo , Sohn Dong‐Ryul , Cho Joo‐Youn , Yu Kyung‐Sang , Shin Sang‐Goo , Paick Jae‐Seung , Jang In‐Jin 
Published: March 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The phosphodiesterase (PDE) type 5 inhibitor is a widely used agent that facilitates penile erection.• Udenafil is newly developed as a PDE‐5 inhibitor. WHAT THIS STUDY ADDS • This is the first study to determine the safety, tolerability and pharmacokinetics of udenafil in healthy subjects.• Udenafil was safe and well tolerated in healthy Korean subjects.• The AUC and Cmax of udenafil increased supraproportionally with increasing dose upon single administration, but there was no significant drug accumulation upon multiple administrations.AIMTo evaluate the safety, tolerability and pharmacokinetics (PK) of udenafil, a novel phosphodiesterase type 5 inhibitor.METHODSA double‐blind, randomized, placebo‐controlled, dose‐rising, parallel‐group, single‐ and multiple‐dose study was conducted in healthy Korean subjects. The subjects were allocated to single‐dose groups of 25, 50, 100, 200 or 300 mg (eight subjects in each dose group, including two placebos), or to multiple‐dose groups of 100 or 200 mg (once‐daily dosing for 7 days; nine subjects in each dose group, including three placebos). Serial samples of blood and urine were collected after oral administration and the drug concentrations in plasma and urine were determined by high‐performance liquid chromatography. Safety and tolerability were evaluated by monitoring clinical laboratory parameters and adverse events.RESULTSUdenafil reached peak plasma concentrations at 0.8–1.3 h, and then declined mono‐exponentially with a terminal half‐life of 7.3–12.1 h in the single‐dose study. The area under the time–concentration curves (AUC) and maximum plasma concentrations (Cmax) increased supraproportionally with increasing dose in the single‐dose study. During multiple dosing, a steady state was reached at 5 days and little accumulation occurred after repeated dosing for 7 days. Udenafil was generally well tolerated in these healthy subjects, and no serious adverse events occurred.CONCLUSIONSUdenafil was safe and well tolerated in healthy volunteers. The AUC and Cmax of udenafil increased supraproportionally with increasing dose upon single administration, but there was no significant drug accumulation upon multiple administrations.
Limited scope for maternal effects in aphid defence against parasitoids
Authors: VORBURGER CHRISTOPH , GEGENSCHATZ SILVAN E. , RANIERI GIULIA , RODRIGUEZ PAULA 
Published: March 2008

Abstract1. A mother’s environment frequently affects her offspring’s phenotype. Such maternal effects may be adaptive, in particular with respect to pathogens or parasites, for example if maternal exposure increases offspring resistance.2. In aphids, maternal effects are likely to occur as a result of their telescoping generations. This study investigated whether maternal effects influence the susceptibility of the peach‐potato aphid,Myzus persicae(Sulzer) (Hemiptera: Aphididae), to its parasitoidDiaeretiella rapae(M’Intosh) (Hymenoptera: Braconidae: Aphidiinae).3. In a first experiment, susceptibility was compared among offspring of aphid mothers that had either no contact to parasitoids, had contact but were not attacked, or were attacked but not mummified. Mothers from the last group had successfully resisted the parasitoid.4. In a second experiment using two different clones, maternal and progeny environment were manipulated by rearing each generation either on a benign (radish) or a more stressful host plant (silver beet) before progeny exposure to parasitoids.5. The first experiment revealed no significant effect of the maternal treatment on offspring susceptibility to parasitoids and thus no evidence for trans‐generational defence. In the second experiment, maternal environment effects were also weak, yet with a trend towards less susceptible offspring of aphid mothers reared on the more stressful plant. However, there was a significant difference among clones and a strong clone × progeny host plant interaction, illustrating that the outcome of a parasitoid attack may be determined by a complex interplay of genetic and environmental factors.6. Overall, the results suggest that there is limited scope for maternal effects in aphid defence against parasitoids.
Keratosis lichenoides chronica in an Indian child following erythroderma
Authors: Ghorpade Ashok 
Published: March 2008

A 4‐year‐old boy presented with mildly itchy, linear, skin lesions over the trunk, arms, and face of 3 months’ duration. He had previously been admitted to a private hospital for generalized exfoliation of the skin following drug intake for fever and throat pain. The nature of the drugs was not known. The exfoliative dermatitis was treated with oral prednisolone, 10 mg daily, tapered over 3 weeks. No further topical or oral medication was given. The present skin lesions started 1 month after the cessation of the steroids. There was no family history of skin lesions, voice changes, or systemic complaints. Cutaneous examination showed multiple violaceous, linear, reticulate ridges with adherent scaling over the chest, back, and neck. There were scaly, flat‐topped papules over the extensor aspects of both upper arms and the buttocks, and scaly plaques over the cheeks (Figs 1a–d and 2a,b). The scalp showed diffuse greasy scaling. There were no oral, genital, axillary, or eye lesions. The nails were normal. Systemic examination did not reveal any abnormal finding.(a,b) Violaceous, linear, reticulate ridges seen over the chest, and scaly papules on the upper arms. (c,d) Reticulate, linear, scaly lesions with flat papules over the back, and scaly papules on the buttocksimageLinear ridges on the neck (a) and scaly plaques on the cheek (b)image Routine hematologic investigations, liver and kidney function tests, tests for hepatitis B and C, and enzyme‐linked immunosorbent assay (ELISA) for HIV were normal. Histopathology from skin lesions on the back revealed hyperkeratosis, patchy parakeratosis, follicular plugging, alternating irregular acanthosis and epidermal thinning, basal cell degeneration, and a band‐like inflammatory infiltrate of lymphocytes, histiocytes, and a few plasma cells (Fig. 3). Based on the classical clinical features and histopathology, keratosis lichenoides chronica was diagnosed, and topical 1% hydrocortisone acetate cream, twice daily, was prescribed. There was slight relief of pruritus at a follow‐up visit after 3 weeks; however, the patient was subsequently lost to follow‐up.Histopathology showing hyperkeratosis, patchy parakeratosis, irregular acanthosis and epidermal thinning, and an upper dermal dense band‐like infiltrate of lymphocytes, histiocytes, and a few plasma cells with melanin incontinence (hematoxylin and eosin; original magnification, ×40)image
Novel uncultured Chloroflexi dechlorinate perchloroethene to trans‐dichloroethene in tidal flat sediments
Authors: Kittelmann Sandra , Friedrich Michael W. 
Published: March 2008

SummaryThe marine environment represents a rich source of bio‐ and geogenically produced organohalogens, including the common pollutant perchloroethene (PCE). However, diversity and function of marine chloroethene‐dechlorinating microorganisms are largely unknown. Here, we have studied the activity and composition of a tidal flat sediment bacterial and archaeal community from the North Sea exposed to low concentrations of PCE. After 2 weeks of incubation, PCE was rapidly dechlorinated via trichloroethene to dichloroethene (DCE). Unexpectedly, these microcosms produced 3.5‐fold more trans‐DCE than cis‐DCE. The actively dechlorinating microbial populations were traced by stable isotope probing of rRNA with 13C‐labelled acetate for 4 days. Terminal restriction fragment length polymorphism fingerprinting and clone libraries of isotopically enriched, ‘heavy’13C‐labelled bacterial 16S rRNA revealed the populations potentially involved in reductive dechlorination. Major clone groups belonged to the Proteobacteria (50.0%; 22.4% δ‐, 12.1% γ‐, 6.9% α‐, 6.9% β‐ and 1.7% ε‐subgroup) and Chloroflexi (29.3%). Populations represented by the two dominant terminal restriction fragments were affiliated with the Dehalococcoidetes (subphylum II of the Chloroflexi), and were exclusively detected in the heavy fraction of the PCE‐dechlorinating incubation. The phylogenetically novel, larger population, designated Tidal Flat Chloroflexi Cluster, was closely related to the recently discovered PCE‐dechlorinating Lahn Cluster bacteria from anoxic river sediment but more distantly related to canonical Dehalococcoides spp. (92–94% sequence identity). The second population was closely related to ‘Dehalobium chlorocoercia DF‐1’. Both populations appear to be responsible for reductive dechlorination of highly chlorinated ethenes to predominantly trans‐DCE in tidal flat sediment incubations.
Colonoscopy for screening and follow up of patients with a family history of colorectal cancer
Authors: Tytherleigh M. G. , Ng V. V. , Mathew L. O. , Banerjee T. , Menon K. V. , Mee A. S. , Farouk R. 
Published: March 2008

AbstractObjective  To determine the minimum family history of colorectal cancer (CRC), which justifies colonoscopy and to establish whether further colonic assessment is necessary after a negative screening colonoscopy.Method  A retrospective review of every colonoscopy undertaken for family screening at the Royal Berkshire and Battle Hospitals, Reading between October 1996 and July 2004.Results  Four hundred and thirty‐two patients (261 women) with an average age of 48 years (range 14–84) were screened. Three cancers in patients over the age of 60 years and 49 adenomas were found in 37 patients. Twenty three of 281 (8%) patients with a ‘low‐risk’ family history (one in 12 or less lifetime risk of developing CRC) had either a cancer or an adenoma. Eighteen of 151 (12%) patients with a ‘high‐risk’ family history (one in 10 or greater) had a similar positive colonoscopy. Thirteen of 15 patients who had an adenoma aged under 45 years had a high‐risk family history. Seventy‐three patients subsequently underwent two or more follow‐up colonoscopies. There were 22 adenomatous polyps found in 12 patients (16%) at the first screening, nine adenomas in seven patients in the second colonoscopy and four adenomas found in four patients in all subsequent colonoscopies.Conclusion  Patients with a low‐risk family history have a similar adenoma pick‐up to that of the general population. These patients need not be screened below the age of 50 unless symptomatic. Follow up of low‐risk family history (FH) patients with a negative screening colonoscopy is unlikely to be beneficial.
Involvement of surgical trainees in surgery for colorectal cancer and their effect on outcome
Authors: Borowski D. W. , Ratcliffe A. A. , Bharathan B. , Gunn A. , Bradburn D. M. , Mills S. J. , Wilson R. G. , Kelly S. B. ,   the members of the Northern Region Colorectal Cancer Audit Group (NORCCAG)
Published: March 2008

AbstractObjective  Surgical training in the UK is undergoing substantial changes. This study assessed: 1) the training opportunities available to trainees in operations for colorectal cancer, 2) the effect of colorectal specialization on training, and 3) the effect of consultant supervision on anastomotic complications, postoperative stay, operative mortality and 5‐year survival.Method  Unadjusted and adjusted comparisons of outcomes were made for unsupervised trainees, supervised trainees and consultants as the primary surgeon in 7411 operated patients included in the Northern Region Colorectal Cancer Audit between 1998 and 2002.Results  Surgery was performed in 656 (8.8%) patients by unsupervised trainees and in 1578 (21.3%) patients by supervised trainees. Unsupervised operations reduced from 182 (12.4%) in 1998 to 82 (6.1%) in 2002 (P < 0.001). Consultants with a colorectal specialist interest were more likely than nonspecialists to be present at surgical resections (OR 1.35, 1.12–1.63, P = 0.001) and to provide supervised training (OR 1.34, 1.17–1.53, P < 0.001). Patients operated on by unsupervised trainees were more often high‐risk patients, however, consultant presence was not significantly associated with operative mortality (OR 0.83, 0.63–1.09, P = 0.186) or survival (HR 1.02, 0.92–1.13, P = 0.735) in risk‐adjusted analysis. Supervised trainees had a case‐mix similar to consultants, with shorter length of hospital stay (11.4 vs 12.4 days, P < 0.001), but similar mortality (OR 0.90, 0.71–1.16, 0.418) and survival (HR 0.96, 0.89–1.05, P = 0.378).Conclusion  One third of patients were operated on by trainees, who were more likely to perform supervised resections in colorectal teams. There was no difference in anastomotic leaks rates, operative mortality or survival between unsupervised trainees, supervised trainees and consultants when case‐mix adjustment was applied. This study would suggest that there is considerable underused training capacity available.
Prosodic Modification and Vocal Adjustments in Mothers' Speech During Face‐to‐face Interaction with Their Two‐ to Four‐month‐old Infants: A Double Video Study
Authors: Braarud Hanne Cecilie , Stormark Kjell Morten 
Published: March 2008

AbstractThe purpose of this study was to examine 32 mothers' sensitivity to social contingency during face‐to‐face interaction with their two‐ to four‐month‐old infants in a closed circuit TV set‐up. Prosodic qualities and vocal sounds in mother's infant‐directed (ID) speech during sequences of live interaction were compared to sequences where expressive behaviours were decoupled by presenting either the mothers (Replay 2) or the infants (Replay 1) with a replay record of the partners' former behaviour in a Live 1–Replay 1–Live 2–Replay 2–Live 3 design. Overall, the mothers produced significantly higher amount of ID speech during the live sequences. Compared to the Live 1 sequence, there was a significant reduction in mothers' ID speech during both replay sequences. However, the mothers only recovered ID speech after the Replay 2 sequence, not after the Replay 1. These findings suggest that the emotions signalled by the mothers' ID speech is affected by the contingency of the infant responses.
Identifying Critical Locations in a Spatial Network with Graph Theory
Authors: Demšar Urška , Špatenková Olga , Virrantaus Kirsi 
Published: March 2008

AbstractEffective management of infrastructural networks in the case of a crisis requires a prior analysis of the vulnerability of spatial networks and identification of critical locations where an interdiction would cause damage and disruption. This article presents a mathematical method for modelling the vulnerability risk of network elements which can be used for identification of critical locations in a spatial network. The method combines dual graph modelling with connectivity analysis and topological measures and has been tested on the street network of the Helsinki Metropolitan Area in Finland. Based on the results of this test the vulnerability risk of the network elements was experimentally defined. Further developments are currently under consideration for eventually developing a risk model not only for one but for a group of co‐located spatial networks.
Efficient Approximation of P‐value of the Maximum of Correlated Tests, with Applications to Genome‐Wide Association Studies
Authors: Li Qizhai , Zheng Gang , Li Zhaohai , Yu Kai 
Published: March 2008

SummaryGenome‐wide association study (GWAS), typically involving 100,000 to 500,000 single‐nucleotide polymorphisms (SNPs), is a powerful approach to identify disease susceptibility loci. In a GWAS, single‐marker analysis, which tests one SNP at a time, is usually used as the first stage to screen SNPs across the genome in order to identify a small fraction of promising SNPs with relatively low p‐values for further and more focused studies. For single‐marker analysis, the trend test derived for an additive genetic model is often used. This may not be robust when the additive assumption is not appropriate for the true underlying disease model. A robust test, MAX, based on the maximum of three trend test statistics derived for recessive, additive, and dominant models, has been proposed recently for GWAS. But its p‐value has to be evaluated through a resampling‐based procedure, which is computationally challenging for the analysis of GWAS. Obtaining the p‐value for MAX with adjustment for the covariates can be even more time‐consuming. In this article, we provide a simple approximation for the p‐value of the MAX test with or without adjusting for the covariates. The new method avoids resampling steps and thus makes the MAX test readily applicable to GWAS. We use simulation studies as well as real datasets on 17 confirmed disease‐associated SNPs to assess the accuracy of the proposed method. We also apply the method to the GWAS of coronary artery disease.
FROM PMTCT TO A MORE COMPREHENSIVE AIDS RESPONSE FOR WOMEN: A MUCH‐NEEDED SHIFT
Authors: EYAKUZE CYNTHIA , JONES DEBRA A. , STARRS ANN M. , SORKIN NAOMI 
Published: March 2008

ABSTRACTHalf of the 33.2 million people living with HIV today are women. Yet, responses to the epidemic are not adequately meeting the needs of women. This article critically evaluates how prevention of mother‐to‐child transmission (PMTCT) programs, the principal framework under which women's health is currently addressed in the global response to AIDS, have tended to focus on the prevention of HIV transmission from HIV‐positive women to their infants. This paper concludes that more than ten years after their inception, PMTCT programs still do not successfully ensure the adequate treatment, care and support of HIV‐infected women. Of particular concern is the continued widespread use of single‐dose nevirapine despite World Health Organization recommendations to employ more effective combination therapies that do not potentially jeopardize women's future treatment outcomes. In response, the article calls for a more comprehensive approach that places women's health needs at the centre of AIDS responses. This is critical in settings where the pandemic is generalized and there is a push to greatly expand PMTCT programs, as a more effective and equitable way of meeting the needs of women in the context of HIV. Without such a comprehensive approach, women will continue to be impacted disproportionately by the pandemic, and current strategies for prevention, including PMTCT, and treatment will not be as effective and responsive as they need to be.