bluuebunny/crossref_metadata_2025 huggingface dataset:
Extending total parenteral nutrition hang time in the neonatal intensive care unit: Is it safe and cost effective?
Authors: Balegar V Kiran Kumar , Azeem Mohammad Irfan , Spence Kaye , Badawi Nadia
Published: December 2012

Aim

To investigate the effects of prolonging hang time of total parenteral nutrition (TPN) fluid on central line–associated blood stream infection (CLABSI), TPN‐related cost and nursing workload.

Methods

A before–after observational study comparing the practice of hanging TPN bags for 48 h (6 February 2009–5 February 2010) versus 24 h (6 February 2008–5 February 2009) in a tertiary neonatal intensive care unit was conducted. The main outcome measures were CLABSI, TPN‐related expenses and nursing workload.

Results

One hundred thirty‐six infants received 24‐h TPN bags and 124 received 48‐h TPN bags. Median (inter‐quartile range) gestation (37 weeks (33,39) vs. 36 weeks (33,39)), mean (±standard deviation) admission weight of 2442 g (±101) versus 2476 g (±104) and TPN duration (9.7 days (±12.7) vs. 9.9 days (±13.4)) were similar (P > 0.05) between the 24‐ and 48‐h TPN groups. There was no increase in CLABSI with longer hang time (0.8 vs. 0.4 per 1000 line days in the 24‐h vs. 48‐h group; P < 0.05). Annual cost saving using 48‐h TPN was AUD 97 603.00. By using 48‐h TPN, 68.3% of nurses indicated that their workload decreased and 80.5% indicated that time spent changing TPN reduced.

Conclusion

Extending TPN hang time from 24 to 48 h did not alter CLABSI rate and was associated with a reduced TPN‐related cost and perceived nursing workload. Larger randomised controlled trials are needed to more clearly delineate these effects.
Fatal Haemophilus influenzae type a sepsis in an infant
Authors: Francis Joshua , Anders Marc , Lobegeier Pam , Nourse Clare
Published: December 2012

Haemophilus influenzae type a can cause severe sepsis, as demonstrated by the case described. Epidemiology of sepsis in childhood is changing. Regardless of the pathogen involved, management of children with septic shock involves resuscitative measures and empiric antibiotics. The following case of H. influenzae type a sepsis proved fatal in spite of appropriate therapy.
Familial hypercholesterolaemia in children and adolescents: A new paediatric model of care
Authors: Martin Andrew C , Coakley John , Forbes David A , Sullivan David R , Watts Gerald F
Published: December 2012

Familial hypercholesterolaemia (FH) is a common genetic disorder affecting more than 8000 children and adolescents throughout Australia. It results in marked elevation in plasma low‐density lipoprotein cholesterol levels from birth that predisposes individuals to premature coronary heart disease in adult life. The majority of children and adolescents with FH are undiagnosed, as symptoms and signs only develop after decades of hypercholesterolaemia. Cascade screening of family members after detecting FH in an index case is an effective approach that allows the diagnosis of FH to be made in the young, before significant atherosclerosis develops. With the availability of effective therapies, mainly statins, paediatricians are ideally placed to improve the outcomes of this disorder by detecting and managing hypercholesterolaemia in childhood, thereby preventing premature coronary artery disease. We describe a new paediatric model of care for FH.
Recurrent fevers
Authors: Isaacs David , Kesson Alison , Lester‐Smith David , Chaitow Jeffrey
Published: December 2012

An 11‐year‐old girl had four episodes of fever in a year, lasting 7–10 days and associated with headache and neck stiffness. She had a long history of recurrent urticaria, usually preceding the fevers. There was also a history of vague pains in her knees and in the small joints of her hands. Her serum C‐reactive protein was moderately raised at 41 g/L (normal <8). Her rheumatologist felt the association of recurrent fevers that lasted 7 or more days with headaches, arthralgia and recurrent urticaria suggested one of the periodic fever syndromes. Genetic testing confirmed she had a gene mutation consistent with one of tumour necrosis factor receptor‐associated periodic syndrome.
Body length shrinkage in an endangered amphibian is associated with drought
Authors: Bendik N. F. , Gluesenkamp A. G.
Published: December 2012

Shrinkage in body length, followed by growth, has rarely been documented in vertebrates and has been associated with stressful energetic and environmental conditions. Here, we document reversible shrinkage in an amphibian for the first time. Jollyville Plateau salamanders Eurycea tonkawae are neotenic (attain maturity while retaining an aquatic larval form) and inhabit springs and caves of a dissected aquifer in Travis County, TX, USA. We conducted mark‐recapture surveys on a spring‐dwelling population before and after an exceptional drought in 2008. Use of unique marks and digital photographs of individuals provided precise information on salamander growth rates during and after a period in which salamanders retreated to underground refugia to avoid desiccation during the drought. Tail width decreased significantly during the drought indicating a reduction in energy stores, a consequence of stressful environmental conditions. Unexpectedly, body length shrinkage also occurred during the drought and was followed by positive growth when spring flow resumed. Body length shrinkage could be an adaptation to coping with long periods of low food availability although its long‐term effects are unknown. Given the influence of body size on many ecological and physiological characteristics of organisms, plasticity in body size may have important consequences that go undetected by researchers if shrinkage is ignored.
Trinity and Apologetics In the Theology of St. Augustine
Authors: Cavadini John C.
Published: December 2012

This article examines Trinitarian themes in St. Augustine's City of God and in his On the Trinity. It argues that the scope and intention of the latter work can be clarified to some extent by noticing the apologetic commitments entailed in the exposition of the doctrine of the Trinity in the former. It argues against the tendency of some recent scholarship to restrict the intelligibility of the On the Trinity to converted Christians, even as it also defends the irreducibility of the doctrine of the Trinity, in Augustine's thinking, to any doctrine of pagan learning. Without prejudice to recent scholarly clarifications of the polemical origins of some of the arguments in the On the Trinity, the article argues (in effect) that the work is more than the sum of its polemical parts, and is intentionally addressed by Augustine to a wide readership, deliberately unspecified in identity except insofar as they are united as “human beings who are seeking God.” Just as ancient apologetics, including Augustine's, was addressed to a variety of people, pagan and Christian, in various states of conviction and conversion, so the On the Trinity is meant to address many types of readers, at various levels of conversion and understanding, hoping to bring all of them closer to—or to confirm and deepen their participation in—the true worship of the one true God, without which, Augustine believes, no one can ultimately find the God they seek.
Love Between Embodiment and Spirituality: Jean‐Luc Marion and John Paul II on Erotic Love
Authors: Tóth Beáta
Published: December 2012

While theological discourse on love traditionally bifurcates between love as a body‐bound passion and its superior and disembodied spiritual counterpart, a growing number of accounts have recently challenged the traditional division arguing for the fundamental unity of the phenomenon of love. Could such a dichotomy be overcome if one reversed the conventional hierarchy between bodily erotic and intellectual agapeic love and made erotic love between man and woman the fundamental paradigm of all kinds of loves? Could the reversal recuperate the affective aspect that has traditionally been downplayed? An answer to these questions is explored through an imaginary dialogue between Jean‐Luc Marion's phenomenology of one‐way erotic love and John Paul II's theology of embodied love.
Intracisternal enzyme replacement therapy in lysosomal storage diseases: dispersal pathways, regional enzyme concentrations and the effect of posttreatment posture
Authors: Jolly R. D. , Marshall N. R. , Marshall J. , Hartman A. , Hemsley K. M. , Winner L. K.
Published: December 2012

Aims

To investigate routes of dispersal of enzyme, its regional uptake and the effect of posture when replacement enzyme is administered directly into the cerebrospinal fluid (CSF).

Methods

Dispersal pathways of particles and solutes were investigated using intracisternal injections of india ink with visual assessment, and a contrast medium (Iohexol) with computer tomography (CT). Replacement enzyme was measured at 46 loci within the central nervous system (CNS) in four groups of dogs subjected to different post‐injection postural changes.

Results

India ink and CT studies showed dispersal pathways for CSF to be mainly via cisterns and sulci. Replacement enzyme reached all areas of the CNS tested, although mean concentrations varied 49‐fold over different areas of the brain. Posttreatment posture had only modest effects on enzyme uptake in limited anatomical sites.

Conclusions

Dispersal of solutes after injection is rapid and initially enhanced by the injection process. Preferential pathways for CSF flow in the subarachnoid spaces of the brain involve cisterns and sulci. The splenial and suprasplenial sulci in particular appear important conduits for dispersal to more dorsal and rostral areas of the brain. Expansion and contraction of these sulci during brain pulsation is considered important to the forward flow of solutes in CSF through these compartments. Following intracisternal enzyme replacement therapy, enzyme reached all areas of the brain, but there was considerable disparity of enzyme uptake with some areas recording much higher levels than others. Posttreatment posture made only modest differences to enzyme uptake.
Methylome of DNase I sensitive chromatin in Populus trichocarpa shoot apical meristematic cells: a simplified approach revealing characteristics of gene‐body DNA methylation in open chromatin state
Authors: Lafon‐Placette Clément , Faivre‐Rampant Patricia , Delaunay Alain , Street Nathaniel , Brignolas Franck , Maury Stéphane
Published: December 2012

DNA methylation is involved in the control of plant development and adaptation to the environment through modifications of chromatin compaction and gene expression. In poplar (Populus trichocarpa), a perennial plant, variations in DNA methylation have been reported between genotypes and tissues or in response to drought. Nevertheless, the relationships between gene‐body DNA methylation, gene expression and chromatin compaction still need clarification.

Here, DNA methylation was mapped in the noncondensed chromatin fraction from P. trichocarpa shoot apical meristematic cells, the center of plant morphogenesis, where DNA methylation variations could influence the developmental trajectory. DNase I was used to isolate the noncondensed chromatin fraction. Methylated sequences were immunoprecipitated, sequenced using Illumina/Solexa technology and mapped on the v2.0 poplar genome. Bisulfite sequencing of candidate sequences was used to confirm mapping data and to assess cytosine contexts and methylation levels.

While the methylated DNase I hypersensitive site fraction covered 1.9% of the poplar genome, it contained sequences corresponding to 74% of poplar gene models, mostly exons. The level and cytosine context of gene‐body DNA methylation varied with the structural characteristics of the genes.

Taken together, our data show that DNA methylation is widespread and variable among genes in open chromatin of meristematic cells, in agreement with a role in their developmental trajectory.
Source–sink dynamics and proteomic reprogramming under elevated night temperature and their impact on rice yield and grain quality
Authors: Shi Wanju , Muthurajan Raveendran , Rahman Hifzur , Selvam Jagadeesh , Peng Shaobing , Zou Yinbin , Jagadish Krishna S. V.
Published: December 2012

High night temperatures (HNTs) can reduce significantly the global rice (Oryza sativa) yield and quality. A systematic analysis of HNT response at the physiological and molecular levels was performed under field conditions.

Contrasting rice accessions, N22 (highly tolerant) and Gharib (susceptible), were evaluated at 22°C (control) and 28°C (HNT). Nitrogen (N) and nonstructural carbohydrate (NSC) translocation from different plant tissues into grains at key developmental stages, and their contribution to yield, grain‐filling dynamics and quality aspects, were evaluated. Proteomic profiling of flag leaf and spikelets at 100% flowering and 12 d after flowering was conducted, and their reprogramming patterns were explored.

Grain yield reduction in susceptible Gharib was traced back to the significant reduction in N and NSC translocation after flowering, resulting in reduced maximum and mean grain‐filling rate, grain weight and grain quality. A combined increase in heat shock proteins (HSPs), Ca signaling proteins and efficient protein modification and repair mechanisms (particularly at the early grain‐filling stage) enhanced N22 tolerance for HNT.

The increased rate of grain filling and efficient proteomic protection, fueled by better assimilate translocation, overcome HNT tolerance in rice. Temporal and spatial proteome programming alters dynamically between key developmental stages and guides future transgenic and molecular analysis targeted towards crop improvement.
Prevalence of Stroke among Patients with Paroxysmal Supraventricular Tachycardia
Authors: BREMBILLA‐PERROT BÉATRICE , DELOBELLE JULIEN
Published: December 2012

Background

To assess the prevalence of unexplained stroke in patients with paroxysmal supraventricular tachycardia (SVT). The risk of atrial fibrillation (AF) is well known and risk of stroke can be expected.

Methods

A total of 1,362 patients were referred for SVT, confirmed by electrophysiological study. Patients with anterograde conduction over accessory pathway (AP) were excluded. Clinical and electrophysiological data were collected.

Results

Stroke was noted in 38 patients with a prevalence of 2.8%. Patients with stroke were older (62 ± 12 years vs 49 ± 19 years; P < 0.0001). Heart disease (34% vs 10%; P < 0.0001) and AF history (10.5% vs 2%; P < 0.001) were more frequent. Male gender was as frequent in patients with and without stroke (45% vs 39.5%; NS). SVT mechanism was similar: AV reentrant tachycardia over concealed AP was 10.5% in patients with stroke and 18.5% in other patients (NS). Atrioventricular node reentrant tachycardias represent other mechanisms. After 2.6 ± 2.5 years, SVT ablation was performed less frequently in patients with stroke (37% vs 63%; P < 0.001); three patients without previous stroke presented a stroke. AF and cardiovascular death were more frequent in patients with stroke (21% vs 4.6%; P < 0.000), (8% vs 2%; P < 0.008). Note that 7.6% of patients treated with ablation and 6% of patients without ablation had an event (stroke, AF, death; NS).

Conclusions

Unexplained stroke was rare in patients with SVT, noted in 2.8% of this population. Old age and AF history were the predictors of stroke. These patients had a risk of adverse events as AF or death. SVT ablation did not seem to reduce the risk of new stroke, AF or death.
Electrical Storm in Children
Authors: CLAUSEN HENNING , PFLAUMER ANDREAS , KAMBERI SULEMAN , DAVIS ANDREW
Published: December 2012

Electrical storm (ES) presents a difficult management problem that has predominantly been described in adults and there are limited published data relating to children. We set out to characterize ES in children to assist management based on published literature and own institutional experience. We retrospectively analyzed the records of children presenting with ES to our institution between July 2001 and July 2011 and conducted a systematic literature review. Four children were identified (median age: 5.7 years, range: 3.3–9.6 years, one male). Each ES was of different character and different management strategies were used. All patients were alive at a median follow‐up of 5.7 years and all had received implantable cardioverter‐defibrillators. Two patients were felt to have catecholaminergic polymorphic ventricular tachycardia, one possible long QT syndrome and one the “short‐coupled” variant of torsades de pointes. At least three of our four patients had possible iatrogenic contribution to their ES. Forty‐seven cases of ES in children with variable management strategies were identified from the published literature. ES is a rare medical emergency in children with multiple etiologies requiring individualized management.
Characteristics of and weaning strategies in tube‐dependent children
Authors: Ishizaki Akiko , Hironaka Shouji , Tatsuno Masaru , Mukai Yoshiharu
Published: December 2012

Background

Despite resolution of the symptoms of eating and/or swallowing disorders, prolonged tube feeding is maintained in some children. This study summarized the characteristics of children with tube dependence and investigated the causes of tube dependence.

Methods

Clinical and growth data were evaluated using medical records and referral forms for 35 tube‐dependent children.

Results

The children in this study had a median age of 30 months (range, 17–37 months) on the first visit and 35.5 months (range, 21.3–44.8 months) at tube removal. Seven children were not weaned from the feeding tube within the study period. Twenty‐two (63%) of the children were girls, 20 (57%) were able to walk, 24 (69%) had mild mental retardation, and 33 (94%) had underlying disease. Tube‐dependent children tended to weigh less than age‐matched normal children. Sixteen children (45.7%) were underweight. Children who had their feeding tubes removed before age 3 were significantly younger at the initial visit than those who had their tubes removed after 3 years of age. Increased finger feeding was observed during the period before tube removal.

Conclusion

Tube‐dependent children tend to be close to normal in body growth and intellectual development. When weaning from tube feeding, interventions at earlier ages are more efficient. Reduction in or discontinuation of tube feeding and encouragement of self‐feeding were effective to wean off tube feeding.
Overexpression of leucine‐rich repeat‐containing G protein‐coupled receptor 5 in gastric cancer
Authors: Yamanoi Kazuhiro , Fukuma Mariko , Uchida Hiroshi , Kushima Ryoji , Yamazaki Ken , Katai Hitoshi , Kanai Yae , Sakamoto Michiie
Published: December 2012

Gastric cancer is one of the most common malignancies worldwide and patients with advanced gastric cancer still have poor clinical outcomes. The overexpression of leucine‐rich repeat‐containing G protein‐coupled receptor 5 (LGR5) mRNA in colorectal cancer and its correlation with clinicopathological factors were recently reported by us. In this study, we show LGR5 mRNA overexpression in human gastric cancer specimens by quantitative RT‐PCR and in situ hybridization and assess a correlation with clinicopathological factors. The mean expression of LGR5 mRNA in cancerous tissues was five times higher than that in normal tissue (P = 0.0002). Furthermore, LGR5 mRNA expression show marked variation among cases and significantly increased in cases where lymphatic invasion was present compared with those where it was absent (P = 0.0056). Although the mean expression level of LGR5 was observed to be higher in nodal metastasis and venous invasion positive cases compared to negative cases, a significant difference was not observed. These results suggest that LGR5 can be a biomarker for malignancy in gastric cancer.
Neuroendocrinological responses to alcohol intoxication in healthy males: Relationship with impulsivity, drinking behavior, and subjective effects
Authors: Magrys S. A. , Olmstead M. C. , Wynne‐Edwards K. E. , Balodis I. M.
Published: December 2012

Ambiguous biochemical and subjective responses to alcohol may relate to preexisting individual differences in alcohol expectations, experience, or impulsivity. This study examined cortisol and alpha‐amylase responses to alcohol and their association with trait impulsivity, alcohol expectancy, and subjective reports of alcohol's effects. Eighty‐seven males assigned to an alcohol, sober, or placebo group provided biochemical and self‐report measures. Both cortisol and alpha‐amylase increased following alcohol administration. Impulsivity correlated with cortisol changes, and the greatest rise in cortisol correlated with high stimulating effects in the alcohol group. These findings emphasize the importance of individual differences in alcohol responses and support a relationship between hormonal responses and alcohol use.
Relationship problems and extradyadic romantic and sexual activity in a web‐sample of Norwegian men and women
Authors: TRÆEN BENTE , THUEN FRODE
Published: December 2012

The purpose of this paper is to describe the prevalence of self‐reported types of extradyadic romantic and sexual activity among adult Norwegians and to explore the role of infidelity in breaking up a permanent relationship. The results are based on 1,001 web interviews with persons ranging in age from 18 to 67 years. The majority of respondents reported having engaged in some kind of extradyadic romantic and/or sexual activity. Forty‐five percent of the women and 39% of the men claimed they had experienced a previous breakup from a marriage or cohabiting relationship. Among those aged 50 years or older, the most important reasons for breaking up a previous relationship were infidelity (38%) and lost love (38%). More men (44%) than women (33%) reported infidelity. Respondents younger than 50 years were more motivated by boredom. Among respondents below the age of 50 years, the most frequently reported reasons for considering termination of a present relationship were quarreling (37%), poor sex life (29%), and “other” reasons (25%). Accordingly, infidelity was not identified as an essential factor for considering a breakup from the present relationship.
Is there an optimal factor structure of the Positive and Negative Syndrome Scale in patients with first‐episode psychosis?
Authors: LANGEVELD JOHANNES , ANDREASSEN OLE A. , AUESTAD BJØRN , FÆRDEN ANN , HAUGE LARS JOHAN , JOA INGE , JOHANNESSEN JAN OLAV , MELLE INGRID , RUND BJORN RISHOVD , RØSSBERG JAN IVAR , SIMONSEN ERIK , VAGLUM PER , LARSEN TOR KETIL
Published: December 2012

The Positive and Negative Syndrome Scale (PANSS) is the most widely used scale to assess a variety of symptoms in patients with schizophrenia and other psychoses. The factor structure of the PANSS has been examined with confirmatory factor analyses in several studies, but not in a well‐defined first‐episode psychosis sample. The aim of this paper is to examine the statistical fit of five different PANSS models in a first‐episode, non‐affective psychosis sample. Confirmatory factor analyses were performed on PANSS data (n = 588). A main criterion for best fit was defined as the Expected Cross Validation Index (ECVI). No tested model revealed an optimally satisfactory model fit index. The Wallwork/Fortgang five‐factor model demonstrated the most optimal psychometric properties. The corresponding subscales of all evaluated five‐factor models were strongly intercorrelated. The Wallwork/Fortgang five‐factor model was found to be statistically and clinically ideal among patients with first‐episode psychosis. Therefore, we recommend this model in forthcoming studies among patients with first‐episode psychosis. However, to prevent the loss of clinically valuable information on an item level, we do not recommend removing any items from the original form. Our study also implies that the specific choice of model will not have a substantial effect on outcome results in studies on the course and outcome in first‐episode psychosis.
Development of anELISAto detect circulating anti‐asparaginase antibodies in dogs with lymphoid neoplasia treated withEscherichia colil‐asparaginase
Authors: Kidd J. A. , Ross P. , Buntzman A. S. , Hess P. R.
Published: December 2012

Resistance toEscherichia colil‐asparaginase in canine lymphoma occurs frequently with repeated administration, a phenomenon often attributed, without substantiation, to the induction of neutralizing antibodies. To test the hypothesis that treated dogs develop antibodies against the drug, we created an enzyme‐linked immunosorbent assay (ELISA) to measure plasma anti‐asparaginase immunoglobulin G responses. Using samples from dogs that had received multiple doses, specific reactivity againstl‐asparaginase was demonstrated, while naïve patients' samples were negative. The optimizedELISAappeared sensitive, with endpoint titers >1 600 000 in positive control dogs. Intra‐ and inter‐assay coefficients of variation were 3.6 and 14.5%. The assay was supported by the observation thatELISA‐positive plasma could immunoprecipitate asparaginase activity. When clinical patients were evaluated, 3/10 dogs developed titers after a single injection; with repeated administration, 4/7 dogs were positive.l‐asparaginase antibodies showed reduced binding to thePEGylateddrug formulation. TheELISAshould prove useful in investigating the potential correlation of antibody responses with resistance.
Imaging and characterization of stretch‐induced ATP release from alveolar A549 cells
Authors: Grygorczyk Ryszard , Furuya Kishio , Sokabe Masahiro
Published: December 2012

Key point

Translation of mechanical forces into biological effects often involves ATP release and activation of the purinergic signalling cascade.

In the lungs, stretch is an important physical stimulus but its impact on ATP release and intercellular signalling is poorly understood.

Here, we report that in the A549 alveolar cell model, a single stretch of more than 10% induces ATP release sufficient to stimulate purinergic receptors on neighbouring cells up to 150 μm away from the source cell.

Stretch‐induced ATP release is significantly enhanced during healing in scratch‐wound areas.

These results demonstrate that mechano‐purinergic signalling may play an important role in modulating alveolar processes, including electrolyte transport, surfactant secretion and wound healing.

Abstract  Mechano‐transduction at cellular and tissue levels often involves ATP release and activation of the purinergic signalling cascade. In the lungs, stretch is an important physical stimulus but its impact on ATP release, the underlying release mechanisms and transduction pathways are poorly understood. Here, we investigated the effect of unidirectional stretch on ATP release from human alveolar A549 cells by real‐time luciferin–luciferase bioluminescence imaging coupled with simultaneous infrared imaging, to monitor the extent of cell stretch and to identify ATP releasing cells. In subconfluent (<90%) cell cultures, single 1 s stretch (10–40%)‐induced transient ATP release from a small fraction (≤1.5%) of cells that grew in number dose‐dependently with increasing extent of stretch. ATP concentration in the proximity (≤150 μm) of releasing cells often exceeded 10 μm, sufficient for autocrine/paracrine purinoreceptor stimulation of neighbouring cells. ATP release responses were insensitive to the putative ATP channel blockers carbenoxolone and 5‐nitro‐2‐(3‐phenylpropyl‐amino) benzoic acid, but were inhibited by N‐ethylmaleimide and bafilomycin. In confluent cell cultures, the maximal fraction of responding cells dropped to <0.2%, but was enhanced several‐fold in the wound/scratch area after it was repopulated by new cells during the healing process. Fluo8 fluorescence experiments revealed two types of stretch‐induced intracellular Ca2+ responses, rapid sustained Ca2+ elevations in a limited number of cells and delayed secondary responses in neighbouring cells, seen as Ca2+ waves whose propagation was consistent with extracellular diffusion of released ATP. Our experiments revealed that a single >10% stretch was sufficient to initiate intercellular purinergic signalling in alveolar cells, which may contribute to the regulation of surfactant secretion and wound healing.
Impact of the fixed gantry angle approximation on dosimetric accuracy for helical tomotherapy plans
Authors: Tudor G. Samuel J. , Thomas Simon J.
Published: December 2012

Purpose:

The purpose of the work was to determine the accuracy of the dose calculation of off‐axis, small target helical tomotherapy treatments using 51 calculation angles, and to determine the increase in calculation angles required to improve the accuracy to acceptable standards.

Methods:

A previously described dose calculation program [S. J. Thomas, K. R. Eyre, G. S. J. Tudor, and J. Fairfoul, “Dose calculation software for helical tomotherapy, utilizing patient CT data to calculate an independent three‐dimensional dose cube,” Med. Phys. 39, – (2012) 10.1118/1.3668061] was modified to permit decomposition of each projection into several subprojections, allowing more accurate modeling of the temporal distribution of fluence within each beamlet. Four plans of small off‐axis spherical targets were recalculated several times with different numbers of subprojections, with the minimum dose to 95% of the PTV (D95%) and the minimum dose to 2% of the PTV (D2%) calculated for each, in order to determine the minimum number of subprojections required for accurate dose statistics. A further nine plans were used to determine the effect on conventional calculation accuracy of varying target size, target position, modulation factor, and pitch. For this analysis, the mean dose and equivalent uniform dose were considered in addition to D95% and D2%.

Results:

The differences between calculations made using the 51 angle approximation and using the closest approximation to real treatment delivery were notable, with up to 11.0% overestimate of D95% for the cases studied. A previously unreported underestimate of dose to parts of the PTV was observed due to this effect, with D2% being underestimated by up to 3.3%. The effect is dependent on target size, position, modulation factor, and the angular distribution of fluence within the sinogram but not pitch. Decomposing each projection into three subprojections left differences in dose statistics that were of reduced magnitude but still appreciable. The effect of increasing the number of subprojections beyond five had little effect.

Conclusions:

When applied to small, off‐axis targets, the limitations of the 51 calculation angle model can substantially affect the veracity of PTV dose statistics, including both underestimation and overestimation of dose depending on position within the PTV. Increasing the number of calculation angles by a factor of 5 reduces the effect to insignificant levels. While the latest release of TomoTherapy planning software will ameliorate the problem, the studied effect is best avoided by positioning small targets near to the bore center. Where this is not possible, it is recommended to ensure a high actual modulation factor and to use an unscaled delivery for patient‐specific quality assurance.
High precision semiautomated computed tomography measurement of lumbar disk and vertebral heights
Authors: Tan Sovira , Yao Jianhua , Yao Lawrence , Ward Michael M.
Published: December 2012

Purpose:

Evaluation of treatments of many spine disorders requires precise measurement of the heights of vertebral bodies and disk spaces. The authors present a semiautomated computer algorithm measuring those heights from spine computed tomography (CT) scans and evaluate its precision.

Methods:

Eight patients underwent two spine CT scans in the same day. In each scan, five thoracolumbar vertebral heights and four disk heights were estimated using the algorithm. To assess precision, the authors computed the differences between the height measurements in the two scans, coefficients of variation (CV), and 95% limits of agreement. Intraoperator and interoperator precisions were evaluated. For local vertebral and disk height measurement (anterior, middle, posterior) the algorithm was compared to a manual mid‐sagittal plane method.

Results:

The mean (standard deviation) interscan difference was as low as 0.043 (0.031) mm for disk heights and 0.044 (0.043) mm for vertebral heights. The corresponding 95% limits of agreement were [−0.085, 0.11] and [−0.10, 0.12] mm, respectively. Intraoperator and interoperator precision was high, with a maximal CV of 0.30%. For local vertebral and disk heights, the algorithm improved upon the precision of the manual mid‐sagittal plane measurement by as much as a factor of 6 and 4, respectively.

Conclusions:

The authors evaluated the precision of a novel computer algorithm for measuring vertebral body heights and disk heights using short term repeat CT scans of patients. The 95% limits of agreement indicate that the algorithm can detect small height changes of the order of 0.1 mm.
Replicating Virus in the Autophagosome
Authors: Ferrarelli Leslie K.
Published: December 2012

Rotavirus initiates, but blocks completion of, autophagy to replicate and assemble new viral particles.
Treatment Duration for Uncomplicated Staphylococcus aureus Bacteremia To Prevent Relapse: Analysis of a Prospective Observational Cohort Study
Authors: Chong Yong Pil , Moon Song Mi , Bang Kyung-Mi , Park Hyun Jung , Park So-Youn , Kim Mi-Na , Park Ki-Ho , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Jeong Jin-Yong , Woo Jun Hee , Kim Yang Soo
Published: December 2012

Practice guidelines recommend at least 14 days of antibiotic therapy for uncomplicated
Staphylococcus aureus
bacteremia (SAB). However, these recommendations have not been formally evaluated in clinical studies. To evaluate the duration of therapy for uncomplicated SAB, we analyzed data from our prospective cohort of patients with SAB. A prospective observational cohort study was performed in patients with SAB at a tertiary-care hospital in Korea between August 2008 and September 2010. All adult patients with SAB were prospectively enrolled and observed over a 12-week period. Uncomplicated SAB was defined as follows: negative results of follow-up blood cultures at 2 to 4 days, defervescence within 72 h of therapy, no evidence of metastatic infection, and catheter-related bloodstream infection or primary bacteremia without evidence of endocarditis on echocardiography. Of 483 patients with SAB, 111 met the study criteria for uncomplicated SAB. Fifty-three (47.7%) had methicillin-resistant SAB. When short-course therapy (<14 days) and intermediate-course therapy (≥14 days) were compared, the treatment failure rates (10/38 [26.3%] versus 16/73 [21.9%]) and crude mortality (7/38 [18.4%] versus 16/73 [21.9%]) did not differ significantly between the two groups. However, short-course therapy was significantly associated with relapse (3/38 [7.9%] versus 0/73;
P
= 0.036). In multivariate analysis, primary bacteremia was associated with a trend toward increased treatment failure (
P
= 0.06). Therefore, in the treatment of uncomplicated SAB, it seems reasonable to consider at least 14 days of antibiotic therapy to prevent relapse, as practice guidelines recommend. Because of its poor prognosis, primary bacteremia, even with a low risk of complication, should not be treated with short-course therapy.
Accessory Gene Regulator (
agr
) Dysfunction in Staphylococcus aureus Bloodstream Isolates from South Korean Patients
Authors: Chong Yong Pil , Kim Eun Sil , Park Su-Jin , Park Ki-Ho , Kim Tark , Kim Mi-Na , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Woo Jun Hee , Jeong Jin-Yong , Kim Yang Soo
Published: December 2012

We describe the genetic and microbiological characteristics of methicillin-resistant
Staphylococcus aureus
(MRSA) bloodstream isolates with
agr
dysfunction from a tertiary-care hospital in Korea. Of these, ST5-SCC
mec
type II-
agr
group II MRSA isolates, which are known to be prevalent in hospital-acquired infections in Korea, were the most abundant, because of the clonal spread of a specific
agr
-defective lineage. This finding suggests that the loss of
agr
function may confer a potential advantage in a hospital setting. Clonal spread of a specific defective-
agr
strain was not observed among community-associated MRSA or methicillin-susceptible
S. aureus
clones, regardless of community or hospital acquisition of infection.
agr
-defective clones, including ST5 and ST239 MRSA, were enriched for heteroresistant vancomycin-intermediate
S. aureus
.
Pharmacokinetics of Intravenous Linezolid in Moderately to Morbidly Obese Adults
Authors: Bhalodi Amira A. , Papasavas Pavlos K. , Tishler Darren S. , Nicolau David P. , Kuti Joseph L.
Published: December 2012

The pharmacokinetics of linezolid was assessed in 20 adult volunteers with body mass indices (BMI) of 30 to 54.9 kg/m
2
receiving 5 intravenous doses of 600 mg every 12 h. Pharmacokinetic analyses were conducted using compartmental and noncompartmental methods. The mean (±standard deviation) age, height, and weight were 42.2 ± 12.2 years, 64.8 ± 3.5 in, and 109.5 ± 18.2 kg (range, 78.2 to 143.1 kg), respectively. Linezolid pharmacokinetics in this population were best described by a 2-compartment model with nonlinear clearance (original value, 7.6 ± 1.9 liters/h), which could be inhibited to 85.5% ± 12.2% of its original value depending on the concentration in an empirical inhibition compartment, the volume of the central compartment (24.4 ± 9.6 liters), and the intercompartment transfer constants (
K
12
and
K
21
) of 8.04 ± 6.22 and 7.99 ± 5.46 h
−1
, respectively. The areas under the curve for the 12-h dosing interval (AUCτ) were similar between moderately obese and morbidly obese groups: 130.3 ± 60.1 versus 109.2 ± 25.5 μg · h/ml (
P
= 0.32), and there was no significant relationship between the AUC or clearance and any body size descriptors. A significant positive relationship was observed for the total volume of distribution with total body weight (
r
2
= 0.524), adjusted body weight (
r
2
= 0.587), lean body weight (
r
2
= 0.495), and ideal body weight (
r
2
= 0.398), but not with BMI (
r
2
= 0.171). Linezolid exposure in these obese participants was similar overall to that of nonobese patients, implying that dosage adjustments based on BMI alone are not required, and standard doses for patients with body weights up to approximately 150 kg should provide AUCτ values similar to those seen in nonobese participants.
Comparison of Six Generic Vancomycin Products for Treatment of Methicillin-Resistant Staphylococcus aureus Experimental Endocarditis in Rabbits
Authors: Tattevin P. , Saleh-Mghir A. , Davido B. , Ghout I. , Massias L. , Garcia de la Maria C. , Miró J. M. , Perronne C. , Laurent F. , Crémieux A. C.
Published: December 2012

Concerns have recently emerged about the potency and the quality of generic vancomycin (VAN) products approved for use in humans, based on experiments in a neutropenic mouse thigh infection model. However, other animal models may be more appropriate to decipher the bactericidal activities of VAN generics
in vivo
and to predict their efficacy in humans. We aimed to compare the bactericidal activities of six generic VAN products currently used in France (Mylan and Sandoz), Spain (Hospira), Switzerland (Teva), and the United States (Akorn-Strides and American Pharmaceutical Products [APP]) in a rabbit model of aortic valve endocarditis induced by 8 × 10
7
CFU of methicillin-resistant
Staphylococcus aureus
(MRSA) strain COL (VAN MIC, 1.5 μg/ml).
In vitro
, there were no significant differences in the time-kill curve studies performed with the six generic VAN products. Ten rabbits in each group were treated with intravenous (i.v.) VAN, 60 mg/kg of body weight twice a day (b.i.d.) for 4 days. Mean peak serum VAN levels, measured 45 min after the last injection, ranged from 35.5 (APP) to 45.9 μg/ml (Teva). Mean trough serum VAN levels, measured 12 h after the last injection, ranged from 2.3 (Hospira) to 9.2 (APP) μg/ml. All generic VAN products were superior to controls (no treatment) in terms of residual organisms in vegetations (
P
< 0.02 for each comparison) and in the spleen (
P
< 0.005 for each comparison). Pairwise comparisons of generic VAN products found no significant differences. In conclusion, a stringent MRSA endocarditis model found no significant differences in the bactericidal activities of six generic VAN products currently used in Europe and America.
In Vitro
and
In Vivo
Activities of 2-Aminopyrazines and 2-Aminopyridines in Experimental Models of Human African Trypanosomiasis
Authors: Vodnala Suman K. , Lundbäck Thomas , Sjöberg Birger , Svensson Richard , Rottenberg Martin E. , Hammarström Lars G. J.
Published: December 2012

New drugs for the treatment of human African trypanosomiasis are urgently needed. A number of 2-aminopyrazines/2-aminopyridines were identified as promising leads following a focused screen of 5,500 compounds for
Trypanosoma brucei
subsp.
brucei
viability. Described compounds are trypanotoxic in the submicromolar range and show comparably low cytotoxicity on representative mammalian cell lines. Specifically, 6-([6-fluoro-3,4-dihydro-2
H
-1-benzopyran-4-yl)]oxy)-
N
-(piperidin-4-yl)pyrazin-2-amine (CBK201352) is trypanotoxic for
T. brucei
subsp.
brucei
,
T. brucei
subsp.
gambiense
, and
T. brucei
subsp.
rhodesiense
and is nontoxic to mammalian cell lines, and
in vitro
preclinical assays predict promising pharmacokinetic parameters. Mice inoculated intraperitoneally (i.p.) with 25 mg/kg CBK201352 twice daily for 10 days, starting on the day of infection with
T. brucei
subsp.
brucei
, show complete clearance of parasites for more than 90 days. Thus, CBK201352 and related analogs are promising leads for the development of novel treatments for human African trypanosomiasis.
Randomized, Open-Label Trial of Primaquine against Vivax Malaria Relapse in Indonesia
Authors: Sutanto Inge , Tjahjono Bagus , Basri Hasan , Taylor W. Robert , Putri Fauziah A. , Meilia Rizka A. , Setiabudy Rianto , Nurleila Siti , Ekawati Lenny L. , Elyazar Iqbal , Farrar Jeremy , Sudoyo Herawati , Baird J. Kevin
Published: December 2012

Radical cure of
Plasmodium vivax
infection applies blood schizontocidal therapy against the acute attack and hypnozoitocidal therapy against later relapse. Chloroquine and primaquine have been used for 60 years in this manner. Resistance to chloroquine by the parasite now requires partnering other blood schizontocides with primaquine. However, the safety and efficacy of primaquine against relapse when combined with other drugs have not been demonstrated. This randomized, open-label, and relapse-controlled trial estimated the efficacy of primaquine against relapse when administered with quinine or dihydroartemisinin-piperaquine for treatment of the acute infection. Among 650 soldiers who had returned to their malaria-free base in Java, Indonesia, after 12 months in malarious Papua, Indonesia, 143 with acute
P. vivax
malaria were eligible for study. One hundred sixteen enrolled subjects were randomized to these treatments: artesunate (200-mg dose followed by 100 mg/day for 6 days), quinine (1.8 g/day for 7 days) plus concurrent primaquine (30 mg/day for 14 days), or dihydroartemisinin (120 mg) plus piperaquine (960 mg) daily for 3 days followed 25 days later by primaquine (30 mg/day for 14 days). Follow-up was for 12 months. One hundred thirteen subjects were analyzable. Relapse occurred in 32 of 41 (78%) subjects administered artesunate alone (2.71 attacks/person-year), 7 of 36 (19%) administered quinine plus primaquine (0.23 attack/person-year), and 2 of 36 (6%) administered dihydroartemisinin-piperaquine plus primaquine (0.06 attack/person-year). The efficacy of primaquine against relapse was 92% (95% confidence interval [CI] = 81% to 96%) for quinine plus primaquine and 98% (95% CI = 91% to 99%) for dihydroartemisinin-piperaquine plus primaquine. Antirelapse therapy with primaquine begun a month after treatment of the acute attack with dihydroartemisinin-piperaquine proved safe and highly efficacious against relapse by
P. vivax
acquired in Papua, Indonesia.
Multicenter Evaluation of the Clinical Outcomes of Daptomycin with and without Concomitant β-Lactams in Patients with Staphylococcus aureus Bacteremia and Mild to Moderate Renal Impairment
Authors: Moise Pamela A. , Amodio-Groton Maria , Rashid Mohamad , Lamp Kenneth C. , Hoffman-Roberts Holly L. , Sakoulas George , Yoon Min J. , Schweitzer Suzanne , Rastogi Anjay
Published: December 2012

Patients with underlying renal disease may be vulnerable to vancomycin-mediated nephrotoxicity and
Staphylococcus aureus
bacteremia treatment failure. In light of recent data demonstrating the successful use of β-lactam plus daptomycin in very difficult cases of
S. aureus
bacteremia, we examined safety and clinical outcomes for patients who received daptomycin with or without concomitant β-lactams. We identified 106 patients who received daptomycin for
S. aureus
bacteremia, had mild or moderate renal insufficiency according to FDA criteria, and enrolled in the Cubicin Outcomes Registry and Experience (CORE), a multicenter registry, from 2005 to 2009. Daptomycin treatment success was 81%. Overall treatment efficacy was slightly enhanced with the addition of a β-lactam (87% versus 78%;
P
= 0.336), but this trend was most pronounced for bacteremia associated with endocarditis or bone/joint infection or bacteremia from an unknown source (90% versus 57%;
P
= 0.061). Factors associated with reduced daptomycin efficacy (by logistic regression) were an unknown source of bacteremia (odds ratio [OR] = 7.59; 95% confidence interval [CI] = 1.55 to 37.2), moderate renal impairment (OR = 9.11; 95% CI = 1.46 to 56.8), and prior vancomycin failure (OR = 11.2; 95% CI = 1.95 to 64.5). Two patients experienced an increase in creatine phosphokinase (CPK) that resolved after stopping daptomycin. No patients developed worsening renal insufficiency related to daptomycin. In conclusion, daptomycin appeared to be effective and well tolerated in patients with
S. aureus
bacteremia and mild to moderate renal insufficiency. Daptomycin treatment efficacy might be enhanced with β-lactam combination therapy in primary endovascular and bone/joint infections. Additional studies will be necessary to confirm these findings.
Role of the NK Cell-Activating Receptor CRACC in Periodontitis
Authors: Krämer Benjamin , Kebschull Moritz , Nowak Michael , Demmer Ryan T. , Haupt Manuela , Körner Christian , Perner Sven , Jepsen Søren , Nattermann Jacob , Papapanou Panos N.
Published: December 2012

Periodontitis is a highly prevalent, biofilm-mediated chronic inflammatory disease that results in the loss of the tooth-supporting tissues. It features two major clinical entities: chronic periodontitis, which is more common, and aggressive periodontitis, which usually has an early onset and a rapid progression. Natural killer (NK) cells are a distinct subgroup of lymphocytes that play a major role in the ability of the innate immune system to steer immune responses. NK cells are abundant in periodontitis lesions, and NK cell activation has been causally linked to periodontal tissue destruction. However, the exact mechanisms of their activation and their role in the pathophysiology of periodontitis are elusive. Here, we show that the predominant NK cell-activating molecule in periodontitis is CD2-like receptor activating cytotoxic cells (CRACC). We show that CRACC induction was significantly more pronounced in aggressive than chronic periodontitis and correlated positively with periodontal disease severity, subgingival levels of specific periodontal pathogens, and NK cell activation
in vivo
. We delineate how
Aggregatibacter actinomycetemcomitans
, an oral pathogen that is causally associated with aggressive periodontitis, indirectly induces CRACC on NK cells via activation of dendritic cells and subsequent interleukin 12 (IL-12) signaling. In contrast, we demonstrate that fimbriae from
Porphyromonas gingivalis
, a principal pathogen in chronic periodontitis, actively attenuate CRACC induction on NK cells. Our data suggest an involvement of CRACC-mediated NK cell activation in periodontal tissue destruction and point to a plausible distinction in the pathobiology of aggressive and chronic periodontitis that may help explain the accelerated tissue destruction in aggressive periodontitis.