bluuebunny/crossref_metadata_2025 huggingface dataset:
Survey of second‐trimester maternal serum screening in Japan
Authors: Okuyama Torayuki , Yotsumoto Junko , Funato Yumi
Published: March 2013

Aim

Second‐trimester maternal serum screening (MSS) is the predominant form of prenatal screening in Japan. We hypothesize that patient education and physician knowledge of Down syndrome (DS) screening are insufficient to provide adequate information regarding prenatal screening in Japan.

Material and Methods

In‐person or telephone interviews with medical personnel were conducted at 25 medical facilities utilizing Afp4 (Esoterix Genetic Laboratories, LLC, a wholly‐owned subsidiary of Laboratory Corporation of America Holdings) second trimester screening. We explored how medical facilities provided information about the MSS process to pregnant women.

Results

Before prenatal testing, 60% of medical facilities spent an average of less than 5 min per patient explaining the MSS process. The option of amniocentesis for chromosomal aneuploidy was explained at nearly all facilities, but only 60% explained the risk of amniocentesis. Ultrasound examination for open neural tube defects was explained only at half the facilities. Only five of 25 (20%) medical practitioners explained the possibility of having congenital disorders fetus.

Conclusion

This study revealed that most obstetricians in Japan do not provide their patients with sufficient information about MSS.
How Do Developmental and Accommodative HRM Enhance Employee Engagement and Commitment? The Role of Psychological Contract and SOC Strategies
Authors: Bal P. Matthijs , Kooij Dorien T. A. M. , De Jong Simon B.
Published: March 2013

In the context of the changing workforce, this study introduced two perspectives on HRM and distinguished universalistic developmental HRM from contingent accommodative HRM. We predicted two separate pathways for the effects on two employee outcomes: work engagement and affective commitment. We expected that developmental HRM would universally relate to employee outcomes by rebalancing the psychological contract between the employee and organization into a less transactional to a more relational contract. We also predicted that accommodative HRM would relate to outcomes only when fulfilling specific needs of employees, associated with their selecting, optimizing, and compensating strategies. Results of a multilevel study among 1058 employees in 17 healthcare units fully supported our expectations regarding the role of the psychological contract. Additionally, we found support for the expected roles of selection and compensation, but not for optimization strategy. This study contributes to the literature by demonstrating that HRM relates to employee outcomes through multiple pathways, which can be either universal or contingent.
URBAN GROWTH EXTERNALITIES AND NEIGHBORHOOD INCENTIVES: ANOTHER CAUSE OF URBAN SPRAWL?*
Authors: Cinyabuguma Matthias , McConnell Virginia
Published: March 2013

ABSTRACT This paper suggests a cause of low density urban development or urban sprawl that has not been given much attention in the literature. There have been a number of arguments put forward for market failures that may account for urban sprawl, including incomplete pricing of infrastructure, environmental externalities, and unpriced congestion. The problem analyzed here is that urban growth creates benefits for an entire urban area, but the costs of growth are borne by individual neighborhoods. An externality problem arises because existing residents perceive the costs associated with the new residents locating in their neighborhoods, but not the full benefits of new entrants which accrue to the city as a whole. The result is that existing residents have an incentive to block new residents to their neighborhoods, resulting in cities that are less dense than is optimal, or too spread out. The paper models several different types of urban growth, and examines the optimal and local choice outcomes under each type. In the first model, population growth is endogenous and the physical limits of the city are fixed. The second model examines the case in which population growth in the region is given, but the city boundary is allowed to vary. We show that in both cases the city will tend to be larger and less dense than is optimal. In each, we examine the sensitivity of the model to the number of neighborhoods and to the size of infrastructure and transportation costs. Finally, we examine optimal subsidies and see how they compare to current policies such as impact fees on new development.
Influence of aminoglycoside antibiotics on chicken cystatin binding to renal brush-border membranes
Authors: Konopska Bogusława , Gburek Jakub , Gołąb Krzysztof , Warwas Maria
Published: March 2013

Objectives

Drug-induced kidney injury is a serious adverse event which needs to be monitored during aminoglycoside therapy. Urine cystatin C is considered an early and sensitive marker of nephrotoxicity. Cystatin C, a low-molecular-weight serum protein, and basic drugs have a common transport system expressed in the apical membrane of renal proximal tubular cells. The aim of this study was to investigate whether aminoglycoside antibiotics influenced cystatin C binding to the renal brush-border membrane.

Methods

The binding study was performed using a rapid filtration technique and affinity column displacement method.

Key findings

Concentration-dependent inhibition of chicken cystatin binding to brush-border membranes by gentamicin was observed. The gentamicin interaction with brush-border membranes was of relatively low affinity (Ki = 32 μm) in comparison with the chicken cystatin affinity to the binding sites (Kd = 3.6 μm). Amikacin and gentamicin were only able to displace chicken cystatin from the chromatographic affinity column in concentrations several times higher than normally found in the tubular fluid during standard aminoglycoside therapy.

Conclusion

Cystatin reabsorption in the proximal tubule cannot be significantly affected by aminoglycoside antibiotics because of their relatively low affinity to common binding sites on the brush-border membrane.
Clinical implications of daytime sleepiness for the academic performance of middle school‐aged adolescents with attention deficit hyperactivity disorder
Authors: Langberg Joshua M. , Dvorsky Melissa R. , Marshall Stephen , Evans Steven W.
Published: March 2013

This study investigated the relative impact of total time slept per night and daytime sleepiness on the academic functioning of 100 middle school‐aged youth (mean age = 11.9) with attention deficit hyperactivity disorder (ADHD). The primary goal of the study was to determine if total time slept per night and/or daytime sleepiness, as measured by youth self‐report on the Pediatric Daytime Sleepiness Scale (PDSS), predicted academic functioning above and beyond symptoms of ADHD and relevant covariates, such as intelligence, achievement scores and parent education level. Self‐reported daytime sleepiness but not self‐reported total time slept per night was associated significantly with all academic outcomes. When examined in a hierarchical regression model, self‐reported daytime sleepiness significantly predicted parent‐rated homework problems and academic impairment and teacher‐rated academic competence above and beyond symptoms of ADHD and relevant covariates, but did not predict grade point average or teacher‐rated academic impairment. The implications of these findings for understanding more clearly the association between ADHD and sleep and the functional implications of this relationship are discussed.
Adiposity, Plasma Insulin, Leptin, Lipids, and Oxidative Stress in Mature Light Breed Horses
Authors: Pleasant R.S. , Suagee J.K. , Thatcher C.D. , Elvinger F. , Geor R.J.
Published: March 2013

Background

Increased blood insulin levels are associated with an increased risk of pasture‐associated laminitis in equids.

Objective

To determine the relationship between plasma insulin, leptin, and lipid levels, and measures of oxidative stress with adiposity in mature light breed horses.

Animals

300 randomly selected light breed horses, aged 4–20 years.

Methods

A random sample of horses (140 mares, 151 geldings, and 9 stallions) was drawn from the VMRCVM Equine Field Service practice client list. Evaluations occurred June 15 – August 15, 2006, with all sampling performed between 0600 and 1200 hours. Concentrate feed was withheld for at least 10 hours before sampling. Plasma was analyzed for insulin, glucose, leptin, triglycerides, nonesterified fatty acids, and measures of oxidative stress. Body condition score was determined as the average of 2 independent investigators.

Results

Overconditioned and obese horses had higher plasma insulin (P < .001) and leptin (P < .01) levels than optimally conditioned horses. Obese horses had higher triglyceride levels (P = .006) and lower red blood cell gluthathione peroxidase activities (P = .001) than optimally conditioned horses.

Conclusions and Clinical Importance

Maintaining horses at a BCS <7 might be important for decreasing the risk of pasture‐associated laminitis.
Evidence‐Based Infection Control In Clinical Practice: If You Buy Clothes for the Emperor, Will He Wear Them?
Authors: Morley P.S.
Published: March 2013

In the fabled story of the Emperor's New Clothes, nakedness is ignored, denied, and accepted despite its obviousness. Similarly, we seemingly have ignored, denied, and accepted the risks of healthcare‐associated infections (HCAI) in veterinary settings, despite common occurrence and obvious importance. Risks for HCAI in veterinary medicine cannot be denied and are increasingly apparent because of improved surveillance and reporting. We have an ethical responsibility to take all reasonable precautions to minimize foreseeable infectious disease hazards, and provide an environment in which personnel and patients are protected from infectious disease hazards so that care can be optimized. Yet, there is often a pronounced mismatch between what we know about risks for infectious disease and our actions. Veterinarians often fail to act on well‐known, universally accepted risks for infectious disease in patients and in people contacting these animals. We must educate personnel so they are well‐versed regarding agents commonly causing HCAI (including zoonotic infections), can identify patients with higher risks for shedding agents and for developing HCAI, have awareness of which procedures and management practices are associated with higher rates of HCAI, and have skill in applying effective prevention methods. We need to develop standardized benchmarks for risks of HCAI in veterinary settings, better understand efficacy and cost‐effectiveness for prevention practices, and develop good educational materials that will promote an effective understanding of risks and prevention methods for HCAI among personnel and the public. We need to buy new clothes for the emperor and be sure he actually wears them!
Effects of the adjunctive probiotic VSL#3 on portal haemodynamics in patients with cirrhosis and large varices: a randomized trial
Authors: Gupta Nitin , Kumar Ashish , Sharma Praveen , Garg Vishal , Sharma Barjesh C. , Sarin Shiv K.
Published: March 2013

Background

Probiotics, by altering gut flora, may favourably alter portal haemodynamics in patients with cirrhosis.

Aim

To investigate the effect of probiotics on portal pressure in patients with cirrhosis.

Methods

Randomized double‐blind placebo‐controlled trial conducted in G.B. Pant Hospital, New Delhi. A total of 94 cirrhotic patients having large oesophageal varices without history of variceal bleeding were randomized to three treatment groups and given 2 months' treatment with propranolol plus placebo, propranolol plus antibiotics (norfloxacin 400 mg BD) or propranolol plus probiotic (VSL#3, 900 billion/day) randomly assigned in 1:1:1 ratio. Outcome measures were change in Hepatic venous pressure gradient (HVPG): Response rate (Percentage of patients having a decrease from baseline of ≥20% or to ≤12 mm Hg) and changes from baseline; biochemical markers of inflammation: changes from baseline.

Results

Adjunctive probiotics increased the response rate compared with propranolol alone (58% vs. 31%, P = 0.046), similar to adjunctive antibiotics (54%). The mean fall in HVPG was greater with either adjunctive probiotics (3.7 mm Hg vs. 2.1 mm Hg, P = 0.061) or adjunctive antibiotics (3.4 mm Hg) than with propranolol alone. Both adjunctive therapies were associated with greater decreases in TNF‐α levels (in both peripheral and hepatic venous blood) that resulted from propranolol‐only treatment. No clinically relevant between‐group differences were observed in the type or frequency of adverse events.

Conclusions

Adjunctive probiotic (VSL#3) improved the response rate to propranolol therapy and was safe and well tolerated in patients with cirrhosis. Adjunctive probiotic therapy merits further study for reduction in portal pressure.
Differential Impact of Dilator Stimuli on Increased Myogenic Activation of Cerebral and Skeletal Muscle Resistance Arterioles in Obese Zucker Rats
Authors: Butcher Joshua T. , Goodwill Adam G. , Stanley Shyla C. , Frisbee Jefferson C.
Published: March 2013

Objective

To use the OZR model of the metabolic syndrome to determine the impact of dilator stimuli on MA of GA and MCA. We tested the hypothesis that increased oxidant stress and TxA2 exacerbate MA, and prevent its blunting with dilator stimuli, in OZR.

Methods

GA/MCA from OZR and LZR was pressurized ex vivo. MA was determined under control conditions and following challenge with acetylcholine, hypoxia, and adenosine. Responses were also evaluated after pre‐treatment with TEMPOL (antioxidant) and SQ‐29548 (PGH2/TxA2 receptor antagonist).

Results

MA was increased (and dilator responses decreased) in GA/MCA from OZR, dependent on the endothelium and ROS. In GA, the impact of ROS on MA and dilator effects was largely via TxA2, while in MCA, this appeared was more dependent on NO bioavailability. Intrinsic responses of GA/MCA to carbacyclin, U46619, and NO donors were similar between strains.

Conclusions

A developing ROS‐based endothelial dysfunction in MCA and GA of OZR contributes to an enhanced MA of these vessels. Although treatment of GA/MCA with TEMPOL attenuates MA in OZR, the mechanistic contributors to altered MA, distal to ROS, differ between the two resistance vessels.
Long‐term Preconditioning with Erythropoietin Reduces Ischemia‐Induced Skin Necrosis
Authors: Rezaeian Farid , Wettstein Reto , Scheuer Claudia , Schenck Thilo L. , Egaña Jose T. , Machens Hans‐Günther , Menger Michael D. , Harder Yves
Published: March 2013

Objective

Recent findings have attested to EPO tissue‐protective effects in ischemically challenged tissues. Therefore, the study aimed at elaborating the effect of systemic pre‐ and postconditioning using EPO in a mouse model of persistent ischemia of the skin.

Methods

Three groups of nine C57Bl/6‐mice each were analyzed. The experimental groups consisted of untreated controls, EPO preconditioning, and EPO postconditioning (500 IU EPO/kg bw/day for 10 days). Critically perfused skin flaps undergoing necrosis, if kept untreated, were mounted into dorsal skinfold chambers. Intravital epi‐fluorescence microscopy was performed for 10 days to assess tissue necrosis, microcirculation, inflammation, and angiogenesis. Protein expression analysis of eNOS was performed. Hematocrit analyses were carried out separately in eight animals.

Results

Only EPO preconditioning was able to significantly reduce necrosis, when compared with controls. This correlated with a significantly increased CD in the critically perfused tissue. Administration of EPO only slightly increased eNOS expression at day 10, when compared with controls. EPO induced angiogenesis and increased hematocrit. Finally, EPO significantly reduced leukocytic inflammation in arterioles in all EPO receiving mice.

Conclusions

EPO preconditioning effectively reduces skin necrosis predominantly by capillary maintenance and reperfusion, as well as improved tissue regeneration. Thus, EPO preconditioning might represent a promising, non‐invasive approach to reduce complications in ischemically challenged skin.
Myenteric neuron numbers are maintained in aging mouse distal colon
Authors: Gamage P. P. K. M. , Ranson R. N. , Patel B. A. , Yeoman M. S. , Saffrey M. J.
Published: March 2013

Background

Age‐associated myenteric neuronal loss has been described in several species. In some studies, cholinergic neurons have been reported to be selectively vulnerable, whereas nitrergic neurons are spared. Aging of the mouse enteric nervous system (ENS) and the subtypes of mouse myenteric neurons that may be lost have been little studied. We therefore investigated changes in the numbers of total neurons and two neuronal subpopulations in the mouse distal colon during aging.

Methods

Wholemount preparations from 3–4‐, 12–13‐, 18–19‐, and 24–25‐month‐old C57BL/6 mice were double immunolabeled with HuC/D antibody to identify the total neuronal population and antisera to either calbindin or neuronal nitric oxide synthase (nNOS) to identify myenteric neuronal subpopulations. Samples were analyzed by confocal microscopy. New procedures were employed to ensure unbiased counting and to correct for changes in gut dimensions with age and stretch during sample preparation. The density of nerve fibers in the tertiary plexus was also studied.

Key Results

No significant change in numbers of total neurons or of either subpopulation with age was measured, but because of gut growth, the density of myenteric neurons decreased between 3–4 and 12–13 months. The density of nNOS‐immunoreactive nerve fibers in the tertiary plexus increased significantly with age, up to 18–19 months. Numerous swollen processes of CB and nNOS‐immunoreactive neurons were observed in 18–19‐ and 24–25‐month‐old animals.

Conclusions & Inferences

These results indicate that aging does not result in a loss of myenteric neurons in mouse distal colon at the ages studied, although neurodegenerative changes, which may impact on neuronal function, do occur.
Stability of quantitative trait loci for growth and wood properties across multiple pedigrees and environments in Eucalyptus globulus
Authors: Freeman Jules S. , Potts Brad M. , Downes Geoffrey M. , Pilbeam David , Thavamanikumar Saravanan , Vaillancourt René E.
Published: March 2013

Eucalypts are one of the most planted tree genera worldwide, and there is increasing interest in marker‐assisted selection for tree improvement. Implementation of marker‐assisted selection requires a knowledge of the stability of quantitative trait loci (QTLs). This study aims to investigate the stability of QTLs for wood properties and growth across contrasting sites and multiple pedigrees of Eucalyptus globulus.

Saturated linkage maps were constructed using 663 genotypes from four separate families, grown at three widely separated sites, and were employed to construct a consensus map. This map was used for QTL analysis of growth, wood density and wood chemical traits, including pulp yield.

Ninety‐eight QTLs were identified across families and sites: 87 for wood properties and 11 for growth. These QTLs mapped to 38 discrete regions, some of which co‐located with candidate genes. Although 16% of QTLs were verified across different families, 24% of wood property QTLs and 38% of growth QTLs exhibited significant genotype‐by‐environment interaction.

This study provides the most detailed assessment of the effect of environment and pedigree on QTL detection in the genus. Despite markedly different environments and pedigrees, many QTLs were stable, providing promising targets for the application of marker‐assisted selection.
Accurate measurement of optical properties of narrow leaves and conifer needles with a typical integrating sphere and spectroradiometer
Authors: NODA HIBIKI M. , MOTOHKA TAKESHI , MURAKAMI KAZUTAKA , MURAOKA HIROYUKI , NASAHARA KENLO NISHIDA
Published: March 2013

Accurate information on the optical properties (reflectance and transmittance spectra) of single leaves is important for an ecophysiological understanding of light use by leaves, radiative transfer models and remote sensing of terrestrial ecosystems. In general, leaf optical properties are measured with an integrating sphere and a spectroradiometer. However, this method is usually difficult to use with grass leaves and conifer needles because they are too narrow to cover the sample port of a typical integrating sphere. Although ways to measure the optical properties of narrow leaves have been suggested, they have problems. We propose a new measurement protocol and calculation algorithms. The protocol does not damage sample leaves and is valid for various types of leaves, including green and senescent. We tested our technique with leaves of Aucuba japonica, an evergreen broadleaved shrub, and compared the spectral data of whole leaves and narrow strips of the leaves. The reflectance and transmittance of the strips matched those of the whole leaves, indicating that our technique can accurately estimate the optical properties of narrow leaves. Tests of conifer needles confirmed the applicability.
Meristem temperature substantially deviates from air temperature even in moderate environments: is the magnitude of this deviation species‐specific?
Authors: SAVVIDES ANDREAS , van IEPEREN WIM , DIELEMAN JANNEKE A. , MARCELIS LEO F. M.
Published: March 2013

Meristem temperature (Tmeristem) drives plant development but is hardly ever quantified. Instead, air temperature (Tair) is usually used as its approximation. Meristems are enclosed within apical buds. Bud structure and function may differ across species. Therefore, Tmeristem may deviate from Tair in a species‐specific way. Environmental variables (air temperature, vapour pressure deficit, radiation, and wind speed) were systematically varied to quantify the response of Tmeristem. This response was related to observations of bud structure and transpiration. Tomato and cucumber plants were used as model plants as they are morphologically distinct and usually growing in similar environments. Tmeristem substantially deviated from Tair in a species‐specific manner under moderate environments. This deviation ranged between −2.6 and 3.8 °C in tomato and between −4.1 and 3.0 °C in cucumber. The lower Tmeristem observed in cucumber was linked with the higher transpiration of the bud foliage sheltering the meristem when compared with tomato plants. We here indicate that for properly linking growth and development of plants to temperature in future applications, for instance in climate change scenarios studies, Tmeristem should be used instead of Tair, as a species‐specific trait highly reliant on various environmental factors.
Statistical Inference for Max-Stable Processes in Space and Time
Authors: Davis Richard A. , Klüppelberg Claudia , Steinkohl Christina
Published: March 2013

Max-stable processes have proved to be useful for the statistical modelling of spatial extremes. Several families of max-stable random fields have been proposed in the literature. One such representation is based on a limit of normalized and rescaled pointwise maxima of stationary Gaussian processes that was first introduced by Kabluchko and co-workers. This paper deals with statistical inference for max-stable space–time processes that are defined in an analogous fashion. We describe pairwise likelihood estimation, where the pairwise density of the process is used to estimate the model parameters. For regular grid observations we prove strong consistency and asymptotic normality of the parameter estimates as the joint number of spatial locations and time points tends to ∞. Furthermore, we discuss extensions to irregularly spaced locations. A simulation study shows that the method proposed works well for these models.
Medication errors in elderly acute care – a systematic review
Authors: Metsälä Eija , Vaherkoski Ulla
Published: March 2013

Aims

Medication safety is a part of quality of care and patient safety. Old age brings many challenges for safe use of medication. In order to improve the prerequisites of medication safety in acute care of the elderly, we systematically reviewed studies to find out what kind of medication errors happen in elderly acute care.

Methods

Cinahl, Medline, Cochrane, JBI Connect+ databases and Finnish healthcare databases Medic and Ohtanen were used in the search. The search was performed using both MeSH terms and keywords by the option ‘search all text’. The original keywords were pharmacy or drugs, medical error or deviation and their Finnish synonyms. These keywords were united to the terms elderly, nursing or acute care or intensive care. Studies published between 2001 and 2011 were chosen.

Results

Medication errors mentioned in the studies were associated with (i) nursing competence, (ii) prescription‐ and patient‐related factors, (iii) medication work organisation and nursing process and (iv) safety culture. This paper presents several practical implications for improving medication safety in the acute care of the elderly.

Limitations

The grey literature was not included because the authors wanted to limit to the best‐quality research. In some studies, elderly acute care was not their exact context or the elderly formed only a part of study population. This may have undermined some types of medication errors typical to elderly acute care.

Conclusions

To improve the prerequisites of medication, safety in acute care of the elderly management of the medication process should be improved. Also, cooperation within the medical team in making the medical care plans and checking out the medication of the elderly people should be improved. This is an important topic of lifelong education for nurses and other healthcare staff as well.
Psychometric evaluation of a questionnaire and primary healthcare nurses' attitudes towards research and use of research findings
Authors: Nilsson Kajermo Kerstin , Alinaghizadeh Hassan , Falk Ulla , Wändell Per , Törnkvist Lena
Published: March 2013

Aim

This article investigates attitudes towards and awareness of research and use of research findings among primary healthcare nurses, determinants of attitudes and evaluation of psychometric properties of an instrument measuring nurses' attitudes.

Background

The production of new knowledge is ongoing and the amount of research of relevance for health care has increased, but there remains a gap between what is known and what is done in practice. To enhance evidence‐based practice and patient safety, the use of research findings needs to be encouraged and promoted.

Method

An explanatory study using a cross‐sectional survey was conducted in 2005–2006. The survey included items about background data and the instrument attitudes towards and awareness of research and development in nursing. 1054 nurses participated in the study. Factor analyses and Cronbach's alpha were used to evaluate internal structure and internal consistency of the instrument.

Result

The nurses generally held positive attitudes towards research. Although most of the nurses reported using research in practice, 37% claimed that they never or rarely used research findings. Half of the respondents perceived they had the ability to analyse scientific reports/articles. This ability and research use were significant determinants of attitudes. Factor analysis of the scale resulted in a three‐factor solution, which differs from the seven‐factor structure previously identified by the originators of the instrument.

Conclusion

Our results support the view that implementation of research is a complex process involving several factors. The different factor structure identified suggests that further work is needed on this instrument.
The novel HLA‐B*44:02:27 allele, identified by sequencing‐based typing of a candidate stem‐cell donor
Authors: van Soest M. , Rosel M. , de Graaff A. , Zwan B. , Spierings E.
Published: March 2013

The HLA‐B*44:02:27 allele strongly resembles the HLA‐B*44:02:01:01 allele with respect to HLA‐C association and haplotype constitution.
Characterization of a novel variant allele HLA‐DPA1*02:02:05, identified in a Chinese Han individual
Authors: He L. , Xu Y. , Wang D. , Deng Z.
Published: March 2013

The novel HLA‐DPA1*02:02:05 allele differs from the closest allele DPA1*02:02:01 by single‐nucleotide change.
Identification of a novel HLA‐B allele HLA‐B*55:34 in a Chinese individual
Authors: Wang L. , Shan X. , Zhixin Z. , Li D. , Li W.
Published: March 2013

The HLA‐B*55:34 allele differs from the closest matching allele B*55:02:01 by one nucleotide substitution in exon 2.
Common and well‐documented HLA alleles: 2012 update to the CWD catalogue
Authors: Mack S. J. , Cano P. , Hollenbach J. A. , He J. , Hurley C. K. , Middleton D. , Moraes M. E. , Pereira S. E. , Kempenich J. H. , Reed E. F. , Setterholm M. , Smith A. G. , Tilanus M. G. , Torres M. , Varney M. D. , Voorter C. E. M. , Fischer G. F. , Fleischhauer K. , Goodridge D. , Klitz W. , Little A.‐M. , Maiers M. , Marsh S. G. E. , Müller C. R. , Noreen H. , Rozemuller E. H. , Sanchez‐Mazas A. , Senitzer D. , Trachtenberg E. , Fernandez‐Vina Marcelo
Published: March 2013

We have updated the catalogue of common and well‐documented (CWD) human leukocyte antigen (HLA) alleles to reflect current understanding of the prevalence of specific allele sequences. The original CWD catalogue designated 721 alleles at the HLA‐A, ‐B, ‐C, ‐DRB1, ‐DRB3/4/5, ‐DQA1, ‐DQB1, and ‐DPB1 loci in IMGT (IMmunoGeneTics)/HLA Database release 2.15.0 as being CWD. The updated CWD catalogue designates 1122 alleles at the HLA‐A, ‐B, ‐C, ‐DRB1, ‐DRB3/4/5, ‐DQA1, ‐DQB1, ‐DPA1 and ‐DPB1 loci as being CWD, and represents 14.3% of the HLA alleles in IMGT/HLA Database release 3.9.0. In particular, we identified 415 of these alleles as being ‘common’ (having known frequencies) and 707 as being ‘well‐documented’ on the basis of ~140,000 sequence‐based typing observations and available HLA haplotype data. Using these allele prevalence data, we have also assigned CWD status to specific G and P designations. We identified 147/151 G groups and 290/415 P groups as being CWD. The CWD catalogue will be updated on a regular basis moving forward, and will incorporate changes to the IMGT/HLA Database as well as empirical data from the histocompatibility and immunogenetics community. This version 2.0.0 of the CWD catalogue is available online at cwd.immunogenomics.org, and will be integrated into the Allele Frequencies Net Database, the IMGT/HLA Database and National Marrow Donor Program's bioinformatics web pages.
Toll‐like receptor 4 genetic variants and prognosis of breast cancer
Authors: Yang C.‐X. , Li C.‐Y. , Feng W.
Published: March 2013

Despite the knowledge of many genetic alterations present in breast cancer, the complexity of this disease precludes placing its biology into a simple conceptual framework. Toll‐like receptor 4 (TLR4) plays important roles in regulating innate immunity and may affect the development of cancers. Polymorphisms in TLR4 gene have been shown to be associated with impaired immune responses. Here, we investigated the association of TLR4 polymorphisms with breast cancer. Four functional TLR4 polymorphisms (−2242T/C, Asp299Gly, Thr399Ile, and +3725G/C) were genotyped in a total of 665 breast cancer patients and 768 healthy controls. Data were analyzed using the chi‐squared test. Results showed that the prevalence of TLR4 +3725GC and CC genotypes were significantly increased in breast cancer cases when compared with controls [odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.08–1.73, P = 0.008 and OR = 2.34, 95% CI = 1.66–3.35, P < 0.0001, respectively]. Also, the frequency of TLR4 +3725C allele was significantly higher in breast cancer patients (P < 0.0001). The −2242T/C polymorphism did not show any significant differences between cases and controls. In addition, when analyzing the survival time of breast cancer patients with TLR4 +3725G/C polymorphism, cases with +3725C allele had significantly shorter survival time overall (P = 0.006). These results suggested that polymorphism in TLR4 gene was associated with increased susceptibility to breast cancer and could be used as a prognostic marker for this malignancy.
Extracorporeal renal replacement therapy and blood purification in critical care
Authors: Cowgill Larry D. , Guillaumin Julien
Published: March 2013

Objective

To review indications methods of renal replacement therapies (RRT) and practical considerations for the creation of aRRTprogram.

Data Sources

Current human and veterinary literature review with a focus on advanced renal physiology and clinical experience inRRTand acute/chronic kidney diseases.

Data Synthesis

Renal replacement therapies encompass intermittent hemodialysis, continuous renal replacement therapy as well as some “hybrid” techniques. Each method ofRRThas practical and theoretical advantages but currently there is no evidence that one technique is superior to the other.

Conclusions

RRTis a valuable therapeutic tool for treatment of acute kidney injury and chronic kidney disease. The implementation of anRRTprogram needs to take into consideration multiple parameters beyond the choice of anRRTplatform.
Risk factors for human immunodeficiency virus infection among Brazilian blood donors: a multicentre case–control study using audio computer‐assisted structured interviews
Authors: de Almeida‐Neto C. , Goncalez T. T. , Birch R. J. , de Carvalho S. M. F. , Capuani L. , Leão S. C. , Miranda C. , Rocha P. C. , Carneiro‐Proietti A. B. , Johnson B. R. , Wright D. J. , Murphy E. L. , Custer B. ,   for NHLBI Retrovirus Epidemiology Donor Study‐II (REDS‐II) International Component, Brazil
Published: March 2013

Background

Although risk factors for HIV infection are known, it is important for blood centres to understand local epidemiology and disease transmission patterns. Current risk factors for HIV infection in blood donors in Brazil were assessed.

Methods

A case–control study was conducted at large public blood centres located in four major cities between April 2009 and March 2011. Cases were persons whose donations were confirmed positive by enzyme immunoassays followed by Western blot confirmation. Audio computer‐assisted structured interviews (ACASI) were completed by all cases and controls. Multivariable logistic regression was used to estimate adjusted odds ratios (AORs) and associated 95% confidence intervals (CIs).

Results

There were 341 cases, including 47 with recently acquired infection, and 791 controls. Disclosed risk factors for both females and males were sex with an HIV‐positive person AOR 11·3, 95% CI (4·1, 31·7) and being an IVDU or sexual partner of an IVDU [AOR 4·65 (1·8, 11·7)]. For female blood donors, additional risk factors were having male sex partners who also are MSM [AOR 13·5 (3·1, 59·8)] and having unprotected sex with multiple sexual partners [AOR 5·19 (2·1, 12·9)]. The primary risk factor for male blood donors was MSM activity [AOR 21·6 (8·8, 52·9)]. Behaviours associated with recently acquired HIV were being a MSM or sex partner of MSM [13·82, (4·7, 40·3)] and IVDU [11·47, (3·0, 43·2)].

Conclusion

Risk factors in blood donors parallel those in the general population in Brazil. Identified risk factors suggest that donor compliance with selection procedures at the participating blood centres is inadequate.
Measuring clinical bleeding using a standardized daily report form and a computer algorithm for adjudication of WHO bleeding grades
Authors: Middelburg R. A. , Ypma P. F. , van der Meer P. F. , van Wordragen‐Vlaswinkel R. J. , Eissen O. , Kerkhoffs J. L.
Published: March 2013

Introduction

Bleeding is increasingly considered an important end point in clinical platelet transfusion studies. Accurate recording and adjudication into well‐defined bleeding grades, however, remains a major challenge.

Methods

We developed a computer algorithm for automatic adjudication. The algorithm's results were compared to those of three independent adjudicators.

Results

For one of 1186 bleeding days, the clinical report form (CRF) was filled out incorrectly, and the algorithm therefore missed one grade‐1 skin bleed. For two bleeding days, the adjudicators incorrectly classified a grade‐2 skin bleed as grade‐1 while the algorithm correctly classified these days. The algorithm saved approximately six person‐hours of adjudication time for the adjudication of 1186 days from 60 patients.

Discussion

The algorithm can be an invaluable tool for adjudicating large amounts of bleeding data.
Dosimetry for nonuniform activity distributions: A method for the calculation of 3D absorbed‐dose distribution without the use of voxel S‐values, point kernels, or Monte Carlo simulations
Authors: Traino A. C. , Marcatili S. , Avigo C. , Sollini M. , Erba P. A. , Mariani G.
Published: March 2013

Purpose:

Nonuniform activity within the target lesions and the critical organs constitutes an important limitation for dosimetric estimates in patients treated with tumor‐seeking radiopharmaceuticals. The tumor control probability and the normal tissue complication probability are affected by the distribution of the radionuclide in the treated organ/tissue. In this paper, a straightforward method for calculating the absorbed dose at the voxel level is described. This new method takes into account a nonuniform activity distribution in the target/organ.

Methods:

The new method is based on the macroscopicS‐values (i.e., the S‐values calculated for the various organs, as defined in the MIRD approach), on the definition of the number of voxels, and on the raw‐count 3D array, corrected for attenuation, scatter, and collimator resolution, in the lesion/organ considered. Starting from these parameters, the only mathematical operation required is to multiply the 3D array by a scalar value, thus avoiding all the complex operations involving the 3D arrays.

Results:

A comparison with the MIRD approach, fully described in the MIRD Pamphlet No. 17, usingS‐values at the voxel level, showed a good agreement between the two methods for 131I and for 90Y.

Conclusions:

Voxel dosimetry is becoming more and more important when performing therapy with tumor‐seeking radiopharmaceuticals. The method presented here does not require calculating theS‐values at the voxel level, and thus bypasses the mathematical problems linked to the convolution of 3D arrays and to the voxel size. In the paper, the results obtained with this new simplified method as well as the possibility of using it for other radionuclides commonly employed in therapy are discussed. The possibility of using the correct density value of the tissue/organs involved is also discussed.
Automatic patient alignment system using 3D ultrasound
Authors: Kaar Marcus , Figl Michael , Hoffmann Rainer , Birkfellner Wolfgang , Hummel Johann , Stock Markus , Georg Dietmar , Goldner Gregor
Published: March 2013

Purpose:

Recent developments in radiation therapy such as intensity modulated radiotherapy (IMRT) or dose painting promise to provide better dose distribution on the tumor. For effective application of these methods the exact positioning of the patient and the localization of the irradiated organ and surrounding structures is crucial. Especially with respect to the treatment of the prostate, ultrasound (US) allows for differentiation between soft tissue and was therefore applied by various repositioning systems, such as BAT or Clarity. The authors built a new system which uses 3D US at both sites, the CT room and the intervention room and applied a 3D/3D US/US registration for automatic repositioning.

Methods:

In a first step the authors applied image preprocessing methods to prepare the US images for an optimal registration process. For the 3D/3D registration procedure five different metrics were evaluated. To find the image metric which fits best for a particular patient three 3D US images were taken at the CT site and registered to each other. From these results an US registration error was calculated. The most successful image metric was then applied for the US/US registration process. The success of the whole repositioning method was assessed by taking the results of an ExacTrac system as golden standard.

Results:

The US/US registration error was found to be 2.99 ± 1.54 mm with respect to the mutual information metric by Mattes (eleven patients) which revealed to be the most suitable of the assessed metrics. For complete repositioning chain the error amounted to 4.15 ± 1.20 mm (ten patients).

Conclusions:

The authors developed a system for patient repositioning which works automatically without the necessity of user interaction with an accuracy which seems to be suitable for clinical application.
Loss of local control due to tumor displacement as a function of margin size, dose–response slope, and number of fractions
Authors: Selvaraj Jothybasu , Uzan Julien , Baker Colin , Nahum Alan
Published: March 2013

Purpose:

Geometric uncertainties are inevitable in radiotherapy. To account for these uncertainties, a margin is added to the clinical target volume (CTV) to create the planning target volume (PTV), and its size is critical for obtaining an optimal treatment plan. Dose‐based (i.e., physical) margin recipes have been published and widely used, but it is important to consider fractionation and the radiobiological characteristics of the tumor when deriving margins. Hence a tumor control probability (TCP)‐based margin is arguably more appropriate.

Methods:

Margins required for ≤1% loss in mean population TCP (relative to a static tumor) for varying numbers of fractions, varying slope of the dose–response curve (γ50) and varying degrees of dose distribution conformity are investigated for spherical and four‐field (4F)‐brick dose distributions. To simulate geometric uncertainties, systematic (Σ) and random (σ) tumor displacements were sampled from Gaussian distributions and applied to each fraction for a spherical CTV. Interfraction tumor motion was simulated and the dose accumulated from fraction to fraction on a voxel‐by‐voxel basis to calculate TCP. PTV margins derived from this work for various fraction numbers and dose–response slopes (γ50) for different degrees of geometric uncertainties are compared with margins calculated using published physical‐dose‐ and TCP‐based recipes.

Results:

Larger margins are required for a decrease in the number of fractions and for an increase in γ50 for both spherical and 4F‐brick dose distributions. However, the margins can be close to zero for the 4F‐brick distribution for small geometric uncertainties (Σ = 1, σ = 1 mm) irrespective of the number of fractions and the magnitude of γ50 due to the higher “incidental” dose outside the tumor. For Σ = 1 mm and σ = 3 mm, physical‐dose‐based recipes underestimate the margin only for the combination of hypofractionated treatments and tumors with a high γ50. For all other situations TCP‐based margins are smaller than physical‐dose‐based recipes.

Conclusions:

Margins depend on the number of fractions and γ50 in addition to Σ and σ. Dose conformity should also be considered since the required margin increases with increasing dose conformity. Ideally margins should be anisotropic and individualized, taking into account γ50, number of fractions, and the dose distribution, as well as estimates of Σ and σ. No single “recipe” can adequately account for all these variables.
Modeling respiratory motion for reducing motion artifacts in 4D CT images
Authors: Zhang Yongbin , Yang Jinzhong , Zhang Lifei , Court Laurence E. , Balter Peter A. , Dong Lei
Published: March 2013

Purpose:

Four‐dimensional computed tomography (4D CT) images have been recently adopted in radiation treatment planning for thoracic and abdominal cancers to explicitly define respiratory motion and anatomy deformation. However, significant image distortions (artifacts) exist in 4D CT images that may affect accurate tumor delineation and the shape representation of normal anatomy. In this study, the authors present a patient‐specific respiratory motion model, based on principal component analysis (PCA) of motion vectors obtained from deformable image registration, with the main goal of reducing image artifacts caused by irregular motion during 4D CT acquisition.

Methods:

For a 4D CT image set of a specific patient, the authors calculated displacement vector fields relative to a reference phase, using an in‐house deformable image registration method. The authors then used PCA to decompose each of the displacement vector fields into linear combinations of principal motion bases. The authors have demonstrated that the regular respiratory motion of a patient can be accurately represented by a subspace spanned by three principal motion bases and their projections. These projections were parameterized using a spline model to allow the reconstruction of the displacement vector fields at any given phase in a respiratory cycle. Finally, the displacement vector fields were used to deform the reference CT image to synthesize CT images at the selected phase with much reduced image artifacts.

Results:

The authors evaluated the performance of the in‐house deformable image registration method using benchmark datasets consisting of ten 4D CT sets annotated with 300 landmark pairs that were approved by physicians. The initial large discrepancies across the landmark pairs were significantly reduced after deformable registration, and the accuracy was similar to or better than that reported by state‐of‐the‐art methods. The proposed motion model was quantitatively validated on 4D CT images of a phantom and a lung cancer patient by comparing the synthesized images and the original images at different phases. The synthesized images matched well with the original images. The motion model was used to reduce irregular motion artifacts in the 4D CT images of three lung cancer patients. Visual assessment indicated that the proposed approach could reduce severe image artifacts. The shape distortions around the diaphragm and tumor regions were mitigated in the synthesized 4D CT images.

Conclusions:

The authors have derived a mathematical model to represent the regular respiratory motion from a patient‐specific 4D CT set and have demonstrated its application in reducing irregular motion artifacts in 4D CT images. The authors’ approach can mitigate shape distortions of anatomy caused by irregular breathing motion during 4D CT acquisition.