bluuebunny/crossref_metadata_2025 huggingface dataset:
Ralstonia solanacearum, a widespread bacterial plant pathogen in the post‐genomic era
Authors: Peeters Nemo , Guidot Alice , Vailleau Fabienne , Valls Marc
Published: May 2013

Ralstonia solanacearum is a soil‐borne bacterium causing the widespread disease known as bacterial wilt. Ralstonia solanacearum is also the causal agent of Moko disease of banana and brown rot of potato. Since the last R. solanacearum pathogen profile was published 10 years ago, studies concerning this plant pathogen have taken a genomic and post‐genomic direction. This was pioneered by the first sequenced and annotated genome for a major plant bacterial pathogen and followed by many more genomes in subsequent years. All molecular features studied now have a genomic flavour. In the future, this will help in connecting the classical field of pathology and diversity studies with the gene content of specific strains. In this review, we summarize the recent research on this bacterial pathogen, including strain classification, host range, pathogenicity determinants, regulation of virulence genes, type III effector repertoire, effector‐triggered immunity, plant signalling in response to R. solanacearum, as well as a review of different new pathosystems.

Taxonomy

Bacteria; Proteobacteria; β subdivision; Ralstonia group; genus Ralstonia.

Disease symptoms

Ralstonia solanacearum is the agent of bacterial wilt of plants, characterized by a sudden wilt of the whole plant. Typically, stem cross‐sections will ooze a slimy bacterial exudate. In the case of Moko disease of banana and brown rot of potato, there is also visible bacterial colonization of banana fruit and potato tuber.

Disease control

As a soil‐borne pathogen, infected fields can rarely be reused, even after rotation with nonhost plants. The disease is controlled by the use of resistant and tolerant plant cultivars. The prevention of spread of the disease has been achieved, in some instances, by the application of strict prophylactic sanitation practices.

Useful websites

Stock centre: International Centre for Microbial Resources—French Collection for Plant‐associated Bacteria CIRM‐CFBP, IRHS UMR 1345 INRA‐ACO‐UA, 42 rue Georges Morel, 49070 Beaucouzé Cedex, France, http://www.angers‐nantes.inra.fr/cfbp/. Ralstonia Genome browser: https://iant.toulouse.inra.fr/R.solanacearum. GMI1000 insertion mutant library: https://iant.toulouse.inra.fr/R.solanacearumGMI1000/GenomicResources. MaGe Genome Browser: https://www.genoscope.cns.fr/agc/microscope/mage/viewer.php?
Woody Debris Amendment Enhances Reclamation after Oil Sands Mining in Alberta, Canada
Authors: Brown Robyn L. , Naeth M. Anne
Published: May 2013

Mining disturbs large forested areas around the world, including boreal forests after oil sands mining in Canada. Industrial companies are expected to reclaim degraded land to ecosystems with equivalent land capability. This research showed the value of woody debris for reclamation of dramatically disturbed landscapes with a forest ecosystem end land use. Adding woody debris during reclamation can facilitate recovery of flora, soil nutrient cycling and water and nutrient holding capacity. Combined with forest floor material, woody debris can provide native plant propagules that would be otherwise commercially unavailable. Sites with and without woody debris on forest floor material containing identifiable litter (L), fragmented and fermented litter (F), and humus (H) (LFH), and peat mineral soil mix (peat) cover soils were studied. Within 2 years, woody debris decreased bare ground and created microsites which were positively associated with greater vegetation cover and woody plant density. Woody debris treatments had lower soil available nitrate and soil under woody debris had a lower temperature range and higher soil volumetric water content than control treatments without woody debris. Woody debris did not affect first year microbial biomass carbon or mycorrhizae, but both were greater on LFH than peat cover soil. LFH was associated with lower bare ground and greater vegetation cover, species richness, and soil phosphorus and potassium than peat cover soil, which had greater soil sulfate.
COMPARISON BETWEEN STANDARD ULTRASONOGRAPHY, ANGLE CONTRAST ULTRASONOGRAPHY, AND MAGNETIC RESONANCE IMAGING CHARACTERISTICS OF THE NORMAL EQUINE PROXIMAL SUSPENSORY LIGAMENT
Authors: Werpy N.M. , Denoix J.M. , McIlwraith C.W. , Frisbie D.D.
Published: May 2013

Previous studies have proposed that standard ultrasonography may not adequately represent the pertinent anatomic characteristics of the equine proximal suspensory ligament. The purpose of the study was to compare the use of standard ultrasonography, angle contrast ultrasonography, MRI, and histology for identification of the anatomic characteristics of the normal equine suspensory ligament in the forelimb. Horses free from forelimb lameness with no palpable abnormalities in the region of the suspensory ligament were included in the study. The proximal suspensory ligaments in 20 forelimbs were examined using the standard ultrasound technique, angle contrast ultrasound technique, and MRI, followed by histologic evaluation. Total transverse (cross‐sectional) area of the proximal suspensory ligament was estimated using the standard ultrasound and the angle contrast ultrasound techniques, MRI, and histologic sections for the following parameters: total area of the ligament, ligament fibers, muscle, and fat. The proximal suspensory ligament lobe size and tissue distribution were compared and subjectively graded (0–4) for asymmetry. Subjectively, angle contrast ultrasound technique improved differentiation of fibers from the remaining tissue types and allowed identification of the peripheral ligament margin. There was no significant difference in asymmetry scores between modalities. The asymmetry scores of the right and left forelimbs were significantly different with both ultrasound and MRI, based on the level of measurement. The angle contrast ultrasound technique has limitations compared to MRI. However, it provides additional diagnostic information that is not available with the standard ultrasound technique.
Dynamic Analysis of a Complex Pneumatic Valve Using Pseudobond Graph Modeling Technique
Authors: Zanj Amir , Hossein Afshari Hamed
Published: May 2013

In this work, the dynamic behaviors of a complex pneumatic reducer valve have been studied through the pseudobond graph modeling technique. This modeling approach graphically describes the energy and mass flows among pneumatic valve components during real operational conditions. State equations have been derived from the pseudobond graph model and have been numerically solved by matlab-Simulink. To validate the accuracy of the model, simulation results are compared with the real data of an experimental setup and good agreements between them are reported. The main advantage of the proposed model over other conventional approaches such as fluid dynamics theories is that it provides a physical model which accurately predicts the system's dynamic responses without any need to run huge computer programs or establish expensive experimental setups.
In Vivo Kinematics of the Extensor Mechanism of the Knee During Deep Flexion
Authors: Kobayashi Koichi , Hosseini Ali , Sakamoto Makoto , Qi Wei , Rubash Harry E. , Li Guoan
Published: May 2013

While various factors have been assumed to affect knee joint biomechanics, few data have been reported on the function of the extensor mechanism in deep flexion of the knee. This study analyzed the patellofemoral joint contact kinematics and the ratio of the quadriceps and patellar tendon forces in living subjects when they performed a single leg lunge up to 150 deg of flexion. The data revealed that in the proximal-distal direction, the patellofemoral articular contact points were in the central one-third of the patellar cartilage. Beyond 90 deg of flexion, the contact points moved towards the medial-lateral edges of the patellar surface. At low flexion angles, the patellar tendon and quadriceps force ratio was approximately 1.0 but reduced to about 0.7 after 60 deg of knee flexion, implying that the patella tendon carries lower loads than the quadriceps. These data may be valuable for improvement of contemporary surgical treatments of diseased knees that are aimed to achieve deep knee flexion.
Multiscale Mechanical Simulations of Cell Compacted Collagen Gels
Authors: Aghvami Maziar , Barocas V. H. , Sander E. A.
Published: May 2013

Engineered tissues are commonly stretched or compressed (i.e., conditioned) during culture to stimulate extracellular matrix (ECM) production and to improve the mechanical properties of the growing construct. The relationships between mechanical stimulation and ECM remodeling, however, are complex, interdependent, and dynamic. Thus, theoretical models are required for understanding the underlying phenomena so that the conditioning process can be optimized to produce functional engineered tissues. Here, we continue our development of multiscale mechanical models by simulating the effect of cell tractions on developing isometric tension and redistributing forces in the surrounding fibers of a collagen gel embedded with explants. The model predicted patterns of fiber reorganization that were similar to those observed experimentally. Furthermore, the inclusion of cell compaction also changed the distribution of fiber strains in the gel compared to the acellular case, particularly in the regions around the cells where the highest strains were found.
Finite Element Analysis of Traction Force Microscopy: Influence of Cell Mechanics, Adhesion, and Morphology
Authors: Zielinski Rachel , Mihai Cosmin , Kniss Douglas , Ghadiali Samir N.
Published: May 2013

The interactions between adherent cells and their extracellular matrix (ECM) have been shown to play an important role in many biological processes, such as wound healing, morphogenesis, differentiation, and cell migration. Cells attach to the ECM at focal adhesion sites and transmit contractile forces to the substrate via cytoskeletal actin stress fibers. This contraction results in traction stresses within the substrate/ECM. Traction force microscopy (TFM) is an experimental technique used to quantify the contractile forces generated by adherent cells. In TFM, cells are seeded on a flexible substrate and displacements of the substrate caused by cell contraction are tracked and converted to a traction stress field. The magnitude of these traction stresses are normally used as a surrogate measure of internal cell contractile force or contractility. We hypothesize that in addition to contractile force, other biomechanical properties including cell stiffness, adhesion energy density, and cell morphology may affect the traction stresses measured by TFM. In this study, we developed finite element models of the 2D and 3D TFM techniques to investigate how changes in several biomechanical properties alter the traction stresses measured by TFM. We independently varied cell stiffness, cell-ECM adhesion energy density, cell aspect ratio, and contractility and performed a sensitivity analysis to determine which parameters significantly contribute to the measured maximum traction stress and net contractile moment. Results suggest that changes in cell stiffness and adhesion energy density can significantly alter measured tractions, independent of contractility. Based on a sensitivity analysis, we developed a correction factor to account for changes in cell stiffness and adhesion and successfully applied this correction factor algorithm to experimental TFM measurements in invasive and noninvasive cancer cells. Therefore, application of these types of corrections to TFM measurements can yield more accurate estimates of cell contractility.
Evaluation of Cell Viability and Functionality in Vessel-like Bioprintable Cell-Laden Tubular Channels
Authors: Yu Yin , Zhang Yahui , Martin James A. , Ozbolat Ibrahim T.
Published: May 2013

Organ printing is a novel concept recently introduced in developing artificial three-dimensional organs to bridge the gap between transplantation needs and organ shortage. One of the major challenges is inclusion of blood-vessellike channels between layers to support cell viability, postprinting functionality in terms of nutrient transport, and waste removal. In this research, we developed a novel and effective method to print tubular channels encapsulating cells in alginate to mimic the natural vascular system. An experimental investigation into the influence on cartilage progenitor cell (CPCs) survival, and the function of printing parameters during and after the printing process were presented. CPC functionality was evaluated by checking tissue-specific genetic marker expression and extracellular matrix production. Our results demonstrated the capability of direct fabrication of cell-laden tubular channels by our newly designed coaxial nozzle assembly and revealed that the bioprinting process could induce quantifiable cell death due to changes in dispensing pressure, coaxial nozzle geometry, and biomaterial concentration. Cells were able to recover during incubation, as well as to undergo differentiation with high-level cartilage-associated gene expression. These findings may not only help optimize our system but also can be applied to biomanufacturing of 3D functional cellular tissue engineering constructs for various organ systems.
Mechanisms of Age-Dependent Response to Winter Temperature in Perennial Flowering of
Arabis alpina
Authors: Bergonzi Sara , Albani Maria C. , Loren van Themaat Emiel Ver , Nordström Karl J. V. , Wang Renhou , Schneeberger Korbinian , Moerland Perry D. , Coupland George
Published: May 2013

Multiple Inputs to Flowering

Perennial plants need to cycle through an extended vegetative phase, in a process known as vernalization, before they initiate flowering.

Bergonzi
et al.

(p.
1094
) and

Zhou
et al.

(p.
1097
) studied how molecular signals translate environmental information—such as exposure to a winter season or changes in daylength and physiological information, such as age of the plant—into signals that promote flowering. In both
Arabis alpina
and
Cardamine flexuosa
, age and vernalization pathways are integrated through the regulation of microRNAs miR156 and miR172.
A Conserved Mechanism for Centromeric Nucleosome Recognition by Centromere Protein CENP-C
Authors: Kato Hidenori , Jiang Jiansheng , Zhou Bing-Rui , Rozendaal Marieke , Feng Hanqiao , Ghirlando Rodolfo , Xiao T. Sam , Straight Aaron F. , Bai Yawen
Published: May 2013

Kinetochore Targeting

Chromosomes must be segregated accurately during cell division. This is facilitated by the attachment of mitotic spindle microtubules to the kinetochore at the chromosomal centromere. The centromere is marked with the histone H3 variant CenH3 (CENP-A in human), and CENP-C forms part of the inner kinetochore.

Kato
et al.

(p.
1110
) used structural biology, biochemistry, and mutagenesis to show that CENP-C recognizes CENP-A chromatin via several different interactions. The CENP-C "central domain" makes close contact with the acidic patch of histones H2A/H2B, and the highly conserved "CENP-C motif" senses both the acidic patch and recognizes the hydrophobicity of the otherwise nonconserved CenH3 tail, supporting a conserved mechanism of centromere targeting by the kinetochore.
What Are Climate Models Missing?
Authors: Stevens Bjorn , Bony Sandrine
Published: May 2013

A better representation of the coupling between atmospheric water and circulation is necessary to reduce imprecision in climate model projections.
Effect of Multivitamin Supplementation on Measles Vaccine Response among HIV-Exposed Uninfected Tanzanian Infants
Authors: Sudfeld Christopher R. , Duggan Christopher , Histed Alex , Manji Karim P. , Meydani Simin N. , Aboud Said , Wang Molin , Giovannucci Edward L. , Fawzi Wafaie W.
Published: May 2013

Immunization and nutritional interventions are mainstays of child health programs in sub-Saharan Africa, yet few published data exist on their interactions. HIV-exposed (but uninfected) infants enrolled in a randomized placebo-controlled trial of multivitamin supplements (vitamins B complex, C, and E) conducted in Tanzania were sampled for an assessment of measles IgG quantity and avidity at 15 to 18 months. Infants were vaccinated between 8.5 and 12 months of age, and all mothers received high-dose multivitamins as the standard of care. Of 201 HIV-exposed infants who were enrolled, 138 (68.7%) were seropositive for measles. There were no effects of infant multivitamin supplementation on measles seroconversion proportions, IgG concentrations, or IgG avidity (
P
> 0.05). The measles seroconversion proportion was greater for HIV-exposed infants vaccinated at 10 to 11 months of age than for those vaccinated at 8.5 to 10 months (
P
= 0.032) and greater for infants whose mothers had a CD4 T-cell count of <200 cells/μl than for infants whose mothers had a CD4 T-cell count of >350 cells/μl (
P
= 0.039). Stunted infants had a significantly decreased IgG quantity compared to nonstunted infants (
P
= 0.012). As for measles avidity, HIV-exposed infants vaccinated at 10 to 11 months had increased antibody avidity compared to those vaccinated at 8.5 to 10 months (
P
= 0.031). Maternal CD4 T-cell counts of <200 cells/μl were associated with decreased avidity compared to counts of >350 cells/μl (
P
= 0.047), as were lower infant height-for-age z-scores (
P
= 0.016). Supplementation with multivitamins containing B complex, C, and E does not appear to improve measles vaccine responses for HIV-exposed infants. Studies are needed to better characterize the impact of maternal HIV disease severity on the immune system development of HIV-exposed infants and the effect of malnutrition interventions on vaccine responses. (This study has been registered at
ClinicalTrials.gov
under registration no. NCT00197730.)
Complete Genome Sequence of Dengue Virus Serotype 4 from Guangzhou, China
Authors: Bai Zhijun , Liu Qi , Jiang Li-yun , Liu Li-cheng , Cao Yi-min , Xu Yang , Jing Qin-long , Luo Lei , Yang Zhi-cong , Jiang Yong-qiang , Chen Wei-jun , Di Biao
Published: May 2013

In 2010, the first complete genome sequence of a dengue virus serotype 4 genotype II strain was reported in Guangzhou, China. Here, we report another isolated strain belonging to the genotype II. Our results will offer help to dengue virus control and precautions.
Meropenem Resistance in Imipenem-Susceptible Meropenem-Resistant Klebsiella pneumoniae Isolates Not Detected by Rapid Automated Testing Systems
Authors: Harino Toshie , Kayama Shizuo , Kuwahara Ryuichi , Kashiyama Seiya , Shigemoto Norifumi , Onodera Makoto , Yokozaki Michiya , Ohge Hiroki , Sugai Motoyuki
Published: May 2013

Klebsiella pneumoniae
showing high resistance to all β-lactams except imipenem, designated as ISMRK (imipenem-susceptible meropenem-resistant
Klebsiella
) is emerging in Japan. The carbapenem resistance of ISMRK cannot be screened by the Vitek and the RAISUS rapid automated susceptibility test systems, which may lead to inappropriate antimicrobial therapy, resulting in compromised patient outcomes.
Three Infectious Viral Species Lying in Wait in the Banana Genome
Authors: Chabannes Matthieu , Baurens Franc-Christophe , Duroy Pierre-Olivier , Bocs Stéphanie , Vernerey Marie-Stéphanie , Rodier-Goud Marguerite , Barbe Valérie , Gayral Philippe , Iskra-Caruana Marie-Line
Published: May 2013

Plant pararetroviruses integrate serendipitously into their host genomes. The banana genome harbors integrated copies of banana streak virus (BSV) named endogenous BSV (eBSV) that are able to release infectious pararetrovirus. In this investigation, we characterized integrants of three BSV species—
Goldfinger
(eBSGFV),
Imove
(eBSImV), and
Obino l'Ewai
(eBSOLV)—in the seedy
Musa balbisiana
Pisang klutuk wulung (PKW) by studying their molecular structure, genomic organization, genomic landscape, and infectious capacity. All eBSVs exhibit extensive viral genome duplications and rearrangements. eBSV segregation analysis on an F1 population of PKW combined with fluorescent
in situ
hybridization analysis showed that eBSImV, eBSOLV, and eBSGFV are each present at a single locus. eBSOLV and eBSGFV contain two distinct alleles, whereas eBSImV has two structurally identical alleles. Genotyping of both eBSV and viral particles expressed in the progeny demonstrated that only one allele for each species is infectious. The infectious allele of eBSImV could not be identified since the two alleles are identical. Finally, we demonstrate that eBSGFV and eBSOLV are located on chromosome 1 and eBSImV is located on chromosome 2 of the reference
Musa
genome published recently. The structure and evolution of eBSVs suggest sequential integration into the plant genome, and haplotype divergence analysis confirms that the three loci display differential evolution. Based on our data, we propose a model for BSV integration and eBSV evolution in the
Musa balbisiana
genome. The mutual benefits of this unique host-pathogen association are also discussed.
Protection against Lethal Influenza with a Viral Mimic
Authors: Baker Steven F. , Guo Hailong , Albrecht Randy A. , García-Sastre Adolfo , Topham David J. , Martínez-Sobrido Luis
Published: May 2013

Despite countermeasures against influenza virus that prevent (vaccines) and treat (antivirals) infection, this upper respiratory tract human pathogen remains a global health burden, causing both seasonal epidemics and occasional pandemics. More potent and safe new vaccine technologies would contribute significantly to the battle against influenza and other respiratory infections. Using plasmid-based reverse genetics techniques, we have developed asingle-cycleinfectiousinfluenzavirus (sciIV) with immunoprotective potential. In our sciIV approach, the fourth viral segment, which codes for the receptor-binding and fusion protein hemagglutinin (HA), has been removed. Thus, upon infection of normal cells, although no infectious progeny are produced, the expression of other viral proteins occurs and is immunogenic. Consequently, sciIV is protective against influenza homologous and heterologous viral challenges in a mouse model. Vaccination with sciIV protects in a dose- and replication-dependent manner, which is attributed to both humoral responses and T cells. Safety, immunogenicity, and protection conferred by sciIV vaccination were also demonstrated in ferrets, where this immunization additionally blocked direct and aerosol transmission events. All together, our studies suggest that sciIV may have potential as a broadly protective vaccine against influenza virus.
IFITM-2 and IFITM-3 but Not IFITM-1 Restrict Rift Valley Fever Virus
Authors: Mudhasani Rajini , Tran Julie P. , Retterer Cary , Radoshitzky Sheli R. , Kota Krishna P. , Altamura Louis A. , Smith Jeffrey M. , Packard Beverly Z. , Kuhn Jens H. , Costantino Julie , Garrison Aura R. , Schmaljohn Connie S. , Huang I-Chueh , Farzan Michael , Bavari Sina
Published: May 2013

We show that interferon-induced transmembrane protein 1 (IFITM-1), IFITM-2, and IFITM-3 exhibit a broad spectrum of antiviral activity against several members of the
Bunyaviridae
family, including Rift Valley fever virus (RVFV), La Crosse virus, Andes virus, and Hantaan virus, all of which can cause severe disease in humans and animals. We found that RVFV was restricted by IFITM-2 and -3 but not by IFITM-1, whereas the remaining viruses were equally restricted by all IFITMs. Indeed, at low doses of alpha interferon (IFN-α), IFITM-2 and -3 mediated more than half of the antiviral activity of IFN-α against RVFV. IFITM-2 and -3 restricted RVFV infection mostly by preventing virus membrane fusion with endosomes, while they had no effect on virion attachment to cells, endocytosis, or viral replication kinetics. We found that large fractions of IFITM-2 and IFITM-3 occupy vesicular compartments that are distinct from the vesicles coated by IFITM-1. In addition, although overexpression of all IFITMs expanded vesicular and acidified compartments within cells, there were marked phenotypic differences among the vesicular compartments occupied by IFITMs. Collectively, our data provide new insights into the possible mechanisms by which the IFITM family members restrict distinct viruses.
Introduction
Authors: Hatheway Allen W.
Published: May 2013

It is with sadness, yet without reservation on the part of this retired soldier, that the findings of the twelve associated chapters in this volume portray a distressing military fact. Again, the traditional peacekeeping nations are flagging in their resolve to support democracy and peace among nations. The new millennium opens to a generational gap in which the young cannot sense that real dictators are far worse than cinema villains. Today’s youth breathes the fresh air purchased by the toil of their oppressed predecessors. Citizens suffer a declining interest in maintenance of armed forces worldwide, yet we must be conscious of the force-multiplication factors that weigh heavily on providing the means for fewer soldiers, sailors, and airmen to keep the peace most effectively through constant and fervent attention to military geology. Professional soldiers and civilian members of the military forces must train more diligently to keep the peace, and must do so with constant regard for preservation of the training environment. First-world military forces now bear serious financial constraints and stringent requirements from their civilian leaders to care for the natural environment during training. I thank the authors for presenting their evidence of the new and expanded roles in conservation, maintenance of training, and preservation of peace at favorable cost-benefit ratios for and by those nations that are dedicated to peace through judicious military strength.
Dating techniques in fault investigations
Authors: Murphy Philip J. , Briedis John , Peck John H.
Published: May 2013

Determining the time of most recent fault movement is an important part of assessing a possible site for a nuclear power plant. The purpose of this paper is not to present research information but to provide a practical guide to some of the dating techniques available to the engineering geologist working on nuclear power plant siting. Emphasis is placed on the practical aspects, such as usable minerals, conditions necessary for them to yield correct dates, degree of accuracy, sample collection, sample size, and sample packaging.

In this paper, we have taken for granted the usual geologic field techniques—such as those used in stratigraphy, paleontology, and structural analysis—for assessing fault history. We discuss laboratory techniques used in conjunction with or supplemental to field methods. The specific radiometric methods discussed are 14C (carbon-14), fission track, K-Ar (potassium-argon), thermoluminescense, Rb-Sr (rubidium-strontium), and U-Th (uranium-thorium). Racemization of amino acids, paleomagnetism, and fluid-inclusion techniques are the nonra-diometric methods that are discussed. Our experiences with some of these techniques are described as well.
Congenital adrenal hyperplasia and early newborn screening: 17α-hydroxyprogesterone (17α-OHP) during the first days of life
Authors: Gruñeiro de Papendieck L , Prieto L , Chiesa A , Bengolea S , Bergadá C
Published: May 2013

Objective Definition of upper limits for 17α-hydroxyprogesterone (17α-OHP) is important as its measurement is used in screening for congenital adrenal hyperplasia. This study aimed at investigating the cut off concentrations in relation to the day of sample collection.

Methods 17α-OHP concentration was determined in dried filter paper blood spots taken from cord blood and by heel pricking up to the sixth day of life. A sensitive fluoroimmunoassay (DELFIA) method was used. Samples from 1091 apparently healthy full term neonates were tested. Samples were separated according to the age of sampling.

Results The 17α-OHP (nmol/l blood) (median and 97.5th centile) concentrations according to the age of sampling were: cord blood (n=126) 123.7, 265.6; first day 0–6 hours (n=30) 49.4, 80.3; 6–12 hours (n=57) 42.7, 79.8; 12–18 hours (n=58) 38.1, 62.7; 18–24 hours (n=67) 28.8, 49.7; second day 24–36 hours (n=51) 23.6, 43.3; 36–48 hours (n=63) 19.9, 35.4; third day (n=200) 10.6, 23.5; fourth day (n=197) 8.8, 20.8; fifth day (n=76) 6.4, 18.3; sixth day (n=166) 6.6, 19.4.

Conclusion Cord 17α-OHP concentrations were very high as previously described, probably owing to steroid production by fetal adrenal glands. Therefore, cord blood is not useful for screening purposes. Thereafter there is a gradual decline in 17α-OHP median concentrations. A cut off value of 30 nmol/l blood was useful in samples obtained after 48 hours of life. However, cut off values before 48 hours should be adjusted according to the sampling time.
Compound heterozygosity Hb S/Hb Hope (β136Gly→Asp): a pitfall in the newborn screening for sickle cell disease
Authors: Ducrocq R , Bévier A , Leneveu A , Elion J , Maier-Redelsperger M , Bardakdjian-Michau J , Badens C , Elion J
Published: May 2013

The presence of Hb Hope associated with Hb S may represent a pitfall (false positive) in the neonatal detection of sickle cell disease by two of the most widely used analytical methods in screening programmes—isoelectric focusing (IEF) and high performance liquid chromatography (HPLC). This example illustrates the need to improve analytical strategies to avoid unnecessary anxiety and summoning of families often from a cultural background in which testing of the father is difficult to obtain. It is suggested that using two independent HPLC procedures might improve the specificity of the screening strategies. Additionally, simple procedures for detection of the most common mutations of the β globin gene on DNA extracted from dried blood specimens could be easily developed for the control of abnormal samples. These procedures could be introduced into the analytical strategy.
Prevalence and molecular basis of α thalassaemia in British South Asians
Authors: Hassall O W , Tillyer M L , Old J M
Published: May 2013

Objectives To determine the prevalence and molecular basis of α thalassaemia in the British South Asian population, and the implications for genetic screening for haemoglobin disorders.

Methods 397 South Asian subjects were screened for haemoglobinopathy with measurement of full blood count, haemoglobin electrophoresis, haemoglobin A2 quantification, and plasma ferritin determination. α Globin gene mapping was successfully performed on 266 stored buffy coat samples using a Southern blot technique after hybridisation with BglII and BamHI.

Results Of the 266 subjects in whom gene mapping was performed, 28 had a single α+ thalassaemia deletion and one was homozygous for this deletion (gene frequency 0.056). Half of the heterozygotes had normal mean cell haemoglobin (MCH) values. A further 16 subjects had probable non-deletional α+ thalassaemia. None had α0 thalassaemia.

Conclusions α Thalassaemia is by far the commonest haemoglobinopathy in British South Asian subjects, but is not a cause of serious genetic risk. Screening and counselling should focus on subjects with more marked red cell hypochromia (MCH <25 pg), thus concentrating resources on subjects of different ethnic origins who may carry the α0 thalassaemia gene.
Evaluation of the effect of breast cancer screening by record linkage with the cancer registry, the Netherlands
Authors: Schouten L J , Schlangen J Th , de Rijke J M , Verbeek A L M
Published: May 2013

Objective To evaluate the effect of a breast cancer screening programme by record linkage with the cancer registry.

Setting Breast cancer screening programme in mid- and southern Limburg, the Netherlands.

Method The data files of the breast cancer screening programme and the Maastricht Cancer Registry were linked in order to evaluate the effect of breast cancer screening. Only the first primary breast tumour was included in the evaluation.

Results From 1990 until 1995 90 001 women participated in the first round of the breast cancer screening programme and 64 637 in subsequent rounds. After the introduction of screening the annual number of breast cancer diagnoses increased by almost 50%. The incidence decreased to previous levels after completion of the first screening round. Record linkage detected 219 interval cancers (within two and a half years of a screening), a proportionate incidence of 31% in the first year and 60% in the second year of the two-year interval between screenings. The incidence of node positive breast cancer was 1% lower in 1994 and 15% lower in 1995 than the incidence in the period 1987–90.

Conclusions Evaluation of the effect of breast cancer screening in the Netherlands can be performed using routinely available cancer registry data. The results of this evaluation seem promising, but further studies are necessary to find ways to reduce the incidence of interval cancer.
Preparation of the first European working standard for phenylalanine determination in dried blood spots
Authors: Dhondt J L , Loeber J G , Elvers L H , Paux E
Published: May 2013

Objective To develop a standard preparation for measurement of phenylalanine in blood spots in phenylketonuria against which manufacturers of kits for phenylalanine determination could calibrate their own blood spot calibrators.

Methods As most of the variation of phenylalanine concentration in dried blood spots is due to the way the blood spot calibrators are prepared, a minimum set of prerequisites for the preparation of blood spot calibrators was established by a group of scientific experts and manufacturers. A “European working standard for phenylalanine in blood spots” (EWS-Phe-01) was prepared and distributed to manufacturers taking part in this project.

Results The control of the homogeneity, linearity, and stability of the EWS-Phe-01 batch gave results within expected ranges. The preliminary results of the recalibration of calibrators for phenylalanine against EWS-Phe-01 by the participating manufacturers were promising; the differences between measurements were much decreased.

Conclusion Manufacturers have agreed to use EWS-Phe-01, and since November 1996 EWS-Phe calibrators have been routinely available from these companies. This pilot study may act as a model for minimising discrepancies found in other screening tests.
Radiation risk of mammography related to benefit in screening programmes: a favourable balance?
Authors: Beemsterboer P M M , Warmerdam P G , Boer R , de Koning H J
Published: May 2013

Objectives To estimate the number of breast cancer deaths induced by low dose radiation in breast cancer screening programmes compared with numbers prevented.

Methods A computer simulation model on the natural history of breast cancer was combined with a model from BEIR-V on induced breast cancer mortality from low levels of radiation. The improvement in prognosis resulting from screening was based on the results of the Swedish overview of the randomised screening trials for breast cancer and the performance of screening in the Netherlands. Different scenarios (ages and intervals) were used to explore the objectives. Sensitivity analyses were carried out for latency period, dose of mammography, sensitivity of the screening test, early detection by screening of induced breast tumours, and new 1996 risk estimates by Howe and McLaughlin.

Results For a screening programme, age group 50–69, two year interval, 2 mGy per view, the balance between the number of deaths induced versus those prevented was favourable: 1:242. When screening is expanded to the age group 40–49 with a one or two year interval the results may be less favourable, that is, 1:66 and 1:97. According to these scenarios and with the Dutch scenario as reference, one breast cancer death from radiation may be expected to occur to save eight extra deaths from breast cancer. If screening was equally effective in young women as in women aged 50–69, the marginal value was 1:±30. Assuming detection of induced cancers by screening could influence the ratios by about 30%, but did not substantially change the conclusions. The new risk estimates by Howe and McLaughlin resulted in five times to eight times favourable ratios breast cancer deaths induced to prevented. Besides age group of screening, dose of mammography is the other determinant of risk.

Conclusions For screening under the age of 50, the balance between the number of breast cancer deaths prevented by screening compared with the number induced by radiation seem less favourable. Credibility intervals were however wide, because of many uncertainties of radiation risk at very low doses.
Performance of antenatal HIV screening strategies in the United Kingdom
Authors: Tookey P A , Gibb D M , Ades A E , Duong T , Masters J , Sherr L , Peckham C S , Hudson C N
Published: May 2013

Background In 1996 only 13.5% of previously undiagnosed HIV infected women were detected in pregnancy. In this study, all 265 maternity units in the United Kingdom were surveyed to determine the relation between screening strategy, uptake of testing, and detection rate.

Methods Data on HIV screening strategy and uptake of testing were collected in 1997 by postal questionnaire. The proportion of women with previously undiagnosed HIV infection identified during pregnancy (detection rate) was calculated using data from national obstetric HIV surveillance and unlinked anonymous seroprevalence studies.

Results 239 (90%) units responded; 25 of these (10%) had a universal offer strategy, 89 (37%) a selective offer, and 125 (52%) tested only women who requested it. All selective units offered testing to injecting drug users, but only 26% to women who had lived abroad in high prevalence areas. Uptake was over 10% in only eight units, all with a universal strategy, and in 76% of selective units it was below 0.1%. The detection rate was 14.7% in universal units, 7.8% in selective units, and 7.7% in on request units. In universal units, detection increased by 6.3% (95% confidence interval 3.7% to 8.8%) for every 10% increase in uptake of testing. There was evidence of both selective presentation for testing and avoidance of testing among infected women.

Conclusions All current antenatal HIV testing strategies fail to identify most infected women. Universal offer strategies achieve a very low uptake and a poor detection rate. Units with selective strategies tend to test only a minority of women at high risk and do not target all the main high risk groups.
Does the frame affect the picture? A study into how attitudes to screening for cancer are affected by the way benefits are expressed
Authors: Sarfati D , Howden-Chapman P , Woodward A , Salmond C
Published: May 2013

Objective To find out how presenting information about the benefits of screening for cancer in different ways affects an individual's decision to accept or reject screening.

Methods A telephone survey of the Wellington region, New Zealand was carried out.

Results A response rate of 75.6% was obtained. Respondents were most likely to accept screening when the benefits of screening were presented as a relative risk reduction. They were most likely to reject screening when the benefits were presented as numbers needed to screen to save one life.

Conclusions An individual's decision about screening for cancer is affected by the way the benefits are framed. Health professionals must choose between framing the benefits of screening in the most positive light, to enhance participation rates, and presenting information in such a way as to reduce framing effects—for example, by expressing the benefits in a variety of forms. Clearly there may be a tension between these approaches; the former is arguably manipulation, and the latter may enhance informed choice, but may also reduce participation rates in screening programmes.
Efficiency of cancer detection during routine repeat (incident) mammographic screening: two versus one view mammography
Authors: Blanks R G , Given-Wilson R M , Moss S M
Published: May 2013

Objective To examine the influence of one view versus two view mammography on cancer detection and recall for further investigation of women attending incident (subsequent) screening.

Setting All cancers (invasive and in situ) detected as incident cases during the second screening round (January 1994 to January 1997) at the South West London Breast Screening Service were used. This service uses two view mammography and double reading, with arbitration by a third or further readers for all screens.

Methods Mammograms of cases were mixed with those of controls in a 1:2 ratio in nine test sets; each set was read independently by three film readers. Fourteen readers, each reading from one to four test sets, took part in the study. Initially, the oblique view only was read, then the craniocaudal view was read in addition. Previous films were available to the readers. Data on abnormalities noted on the films and probability of recall were recorded and analysed.

Results 10 of the 14 readers obtained increased sensitivity using two views (p=0.04), for two readers there was no difference, and for two readers sensitivity decreased. The mean sensitivity increase was 6.1% (p=0.01). The overall increase in sensitivity from all readings of invasive cancers was 8.9%, with no increase seen for in situ cancers. 11 of the 14 readers obtained an increase in specificity (p=0.006), two readers showed no increase, and the specificity for one reader was decreased. The mean increase in specificity using two views was 5.7% (p=0.006).

Conclusion This study showed an increase of 8.9% in sensitivity for the detection of invasive cancers when two views are used at incident screening, with a ratio of two control mammograms for every case. This is equivalent to a sample from population screening with a cancer detection rate of 333 per 1000. Such a study is considered to be likely to underestimate the benefit of two views in screening under non-test conditions where the cancer detection rate is of the order of five per 1000. The use of two view mammography for the detection of in situ cancers showed no increased benefit. A randomised controlled trial is needed to obtain a reliable estimate of the increase in cancer detection rate for incident screening in normal populations.
General population screening for infection with Helicobacter pylori: a realistic option?
Authors: Stone M A , Barnett D B , Mayberry J F
Published: May 2013

Objectives To consider the effectiveness of a community programme of Helicobacter pylori (H pylori) screening and eradication run in collaboration with general practitioners. Specifically, to assess numbers successfully eradicating H pylori and consequently reducing the prevalence of infection, and to identify and consider areas of poor compliance.

Setting A large general practice in Market Harborough, Leicestershire, UK.

Methods A general population sample of 4015 subjects aged 21–55 was offered a serological screening test for H pylori through their general practitioners. Those testing positive were offered a prescription for eradication treatment and an information pack designed to encourage good compliance. Successful eradication was assessed by a urea breath test.

Results The screening test was accepted by 1566 (39%) of those invited, with men and younger people least likely to attend. Of the 235 (15%) subjects who tested positive, 186 (79%) were treated and eradication was confirmed in 170 (95%) of the 179 subjects who had a urea breath test. Overall, eradication was confirmed in 4% (170/4015) of those offered screening. Assuming a 15% overall prevalence of H pylori infection, it is estimated that H pylori was eradicated in 29% of those infected in the target group.

Conclusions When an intervention was used to encourage good compliance, the eradication rate was high. Effectiveness was limited most strongly by the acceptance rate for the screening test, but also by the rate of uptake of eradication treatment. If benefits of population screening can be shown, appropriate interventions to improve compliance in these areas would need consideration.
Analysis of 31 CFTR mutations by polymerase chain reaction/oligonucleotide ligation assay in a pilot screening of 4476 newborns for cystic fibrosis
Authors: Gasparini P. , Arbustini E. , Restagno G. , Zelante L. , Stanziale P. , Gatta L. , Sbaiz L. , Sedita A.M. , Banchieri N. , Sapone L. , Fiorucci G.C. , Brinson E. , Shulse E. , Rappaport E. , Fortina P.
Published: May 2013

Objectives Molecular biological testing for genetic diseases has grown rapidly, but speed, accuracy, specificity, sensitivity, throughput, and cost become more important as large scale screening is considered. This is a pilot study of an assay for the simultaneous detection of up to 31 cystic fibrosis mutations in a multicentre population based screening of 4476 Italian newborns.

Methods The assay is a polymerase chain reaction, followed by an oligonucleotide ligation assay (PCR/OLA) and finally a sequence coded separation. It allows the detection of up to 31 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Guthrie spots were used as a source of template DNA.

Results 144 carriers were detected during the analysis of 4476 samples, which translates into a carrier frequency of 1/31.1. Forty two carriers were detected from 1341 samples in Pavia (1/31.9), 53 from 1574 in Turin (1/29.7), and 49 from 1561 in San Giovanni Rotondo (1/31.8). Fifteen different mutations were detected, the most common being ΔF508 (0.625). Other common mutations included G542X (16 of 144), which was particularly common in southern Italy (14 of 49), N1303K (8 of 144), and R117H (8 of 144), detected only in the northern centres.

Conclusions PCR/OLA is a robust, accurate, user friendly method for cystic fibrosis screening of newborns using blood spots in a semiautomated way at a low cost per mutation (0.8 Euro).
Neonatal screening for congenital hypothyroidism in Mexico: experience, obstacles, and strategies
Authors: Vela M. , Gamboa S. , Loera-Luna A. , Aguirre B.E. , Pérez-Palacios G. , Velázquez A.
Published: May 2013

Objective To report the experience, obstacles, and strategies of screening for congenital hypothyroidism.

Setting Newborns in Mexico.

Methods Thyroid stimulating hormone (TSH) was measured by enzyme immunoassay using commercial kits in 1 140 364 newborns.

Results There were 464 positive cases, of whom 299 (64.4%) were girls. 236 (50.9% showed ectopic nodules, 202 (43.5%) thyroid agenesis, 21 (4.5%) dyshormonogenesis, and 5 (1.1%) an unclassified goitre. The false positive rate was 0.024% and there were 11 false negative results. Currently, 600 000 (26%) of the 2 300 000 newborns are screened. This percentage has been increased in recent years by taking samples from cord blood and will be increased further by starting congenital hypothyroidism screening at social security units and by midwives screening infants born at home.

Conclusions Mental retardation in infants in developing countries can be reduced by neonatal screening, and carefully planned strategies can steadily extend the benefits of screening.