Internal References Research Articles

The determination of nest depth in founding queens of leaf-cutting ants (Atta vollenweideri): idiothetic and temporal control

Leaf-cutting ant queens excavate a founding nest consisting of a vertical tunnel and a final horizontal chamber. Nest foundation is very time consuming, and colony success depends on the excavated depth. Although shallow nests may be energetically cheaper to dig, queens may be more exposed to the changing environment. Deeper chambers, in contrast, may be climatically more stable, but are more expensive to dig. We investigated the mechanisms underlying the control of nest depth in queens of the leaf-cutting ant Atta vollenweideri. We focused on the use of internal information for the control of nest depth, and therefore maintained the soil and environmental conditions invariant during the different laboratory experiments. We compared the tunnel lengths excavated by queens that were able to complete their nests earlier, faster or slower than under standard conditions. An earlier and faster nest completion was obtained by offering queens either pre-excavated tunnels of different lengths, soils at different temperatures, or soft sandy soils. A slower nest excavation was induced by offering queens harder dry soils, and by delaying the start of digging several days after the nuptial flight. Results indicate that the determination of nest depth was a regulated process involving the use of internal references: queens excavated their tunnels either until a particular depth was reached or for some predetermined length of time. Queens appear to monitor their movements while walking up und down the tunnel, and to compare this sensory information with a motor command that represents a preset tunnel length to be excavated before switching to chamber digging. In addition to this form of idiothetic control, results indicate that the elapsed digging time also feeds back onto the control system. It is argued that the determination of nest depth, i.e. the transition from tunnel to chamber digging, is initiated either after a preset tunnel length is reached, or as soon as a maximal time interval has elapsed, irrespective of the excavated tunnel length. A control system using both idiothetic and temporal information, as demonstrated in the present study, allows queens to flexibly react to different soil conditions, and therefore avoid excessive time and energy investments. Possible mechanisms underlying the control of chamber size are also discussed.

111 THE COMBINATION OF GENETIC VARIANTS IN PRO-INFLAMMATORY CYTOKINES PREDICTS THE RISKS OF DEATH AND HEPATOCELLULAR CARCINOMA OCCURRENCE IN PATIENTS WITH HCV-RELATED CIRRHOSIS

Background and Aim: The prevalence of childhood overweight has reached epidemic proportions around the globe. In parallel with the obesity epidemic, non-alcoholic fatty liver disease has increased, and has now become the most common cause of liver disease in children. The epidemic of childhood overweight is of great concern because, in addition to these adverse effects on the liver in childhood, overweight in childhood may also affect the risk of liver disease in adulthood. Therefore we investigated if childhood body size from the ages of 7 to 13 years was associated with the risk of hepatocellular carcinoma (HCC) in adulthood. Methods: Individuals were 165,540 men and 160,883 women born between 1930 and 1989 from the Copenhagen School Health Records Register. Information on HCC was obtained by linkage to the Danish Cancer Registry. Anthropometry was measured by school doctors or nurses, and body mass index (BMI) z-scores were calculated from internal ageand sex-specific references. Hazard ratios (HR) (95% confidence intervals) of HCC were calculated from Cox proportional hazard models. Results: During follow-up, there were 252 cases of HCC. At 7 years of age, the HR of HCC in adulthood was 1.12 (0.97, 1.29) per 1-unit increase in BMI z-score. By age 13 years, the HR of HCC was 1.25 (1.09, 1.44) per 1-unit increase in BMI z-score. Associations were similar in boys and girls, consistent across year of birth and essentially unchanged by exclusion of individuals with hepatitis B and C, alcoholic conditions and biliary diseases. Conclusion: Childhood BMI is positively associated with the risk of HCC in adulthood. The risk is present in both boys and girls, and increase slightly with increasing age of the children. The epidemic of childhood overweight is alarming because, in addition to the many adverse metabolic effects in childhood, the epidemic may also translate into a large number of adverse health effects in adulthood, such as cardiovascular disease and liver cancer. Acknowledgement: This work is funded by and carried out as a part of FLIP (fatty liver inhibition of progression) under the Seventh Framework Programme (FP7/2007–2013, grant agreement no. Health-F2–2009–241762.

Methionine Scanning as an NMR Tool for Detecting and Analyzing Biomolecular Interaction Surfaces

Methyl NMR spectroscopy is a powerful tool for studying protein structure, dynamics, and interactions. Yet difficulties with resonance assignment and the low abundance of methyl groups can preclude detailed NMR studies, particularly the determination of continuous interaction surfaces. Here we present a straightforward strategy that overcomes these problems. We systematically substituted solvent-exposed residues with reporter methionines in the expected binding site and performed chemical shift perturbation (CSP) experiments using methyl-TROSY spectra. We demonstrate the utility of this approach for the interaction between the HECT domain of the Rsp5p ubiquitin ligase and its cognate E2, Ubc4. Using these mutants, we could instantaneously assign all newly arising reporter methyl signals, determine the Ubc4 interaction surface on a per-residue basis, and investigate the importance of each individual mutation for ligand binding. Our data show that methionine scanning significantly extends the applicability, information content, and spatial resolution of methyl CSP experiments.

Synthesis of fluorinated maltose derivatives for monitoring protein interaction by 19F NMR

A novel reporter system, which is applicable to the 19F NMR investigation of protein interactions, is presented. This approach uses 2-F-labeled maltose as a spy ligand to indirectly probe protein–ligand or protein–protein interactions of proteins fused or tagged to the maltose-binding protein (MBP). The key feature is the simultaneous NMR observation of both 19F NMR signals of gluco/manno-type-2-F-maltose-isomers; one isomer (α-gluco-type) binds to MBP and senses the protein interaction, and the nonbinding isomers (β-gluco- and/or α/β-manno-type) are utilized as internal references. Moreover, this reporter system was used for relative affinity studies of fluorinated and nonfluorinated carbohydrates to the maltose-binding protein, which were found to be in perfect agreement with published X-ray data. The results of the NMR competition experiments together with the established correlation between 19F chemical shift data and molecular interaction patterns, suggest valuable applications for studies of protein–ligand interaction interfaces.

Reduction of Systematic Uncertainty in DFT Redox Potentials of Transition-Metal Complexes

Reliable calculations of redox potentials could provide valuable insight into catalytic mechanisms of electrochemically active transition-metal complexes as well as guidelines for the design of new electrocatalysts. However, the correlation between theoretical and experimental data is often uncertain, since redox properties depend strongly on experimental conditions of electrochemical measurements, including the nature of the solvent, electrolyte, and working electrode. Here, we show that the use of internal references allows for quantitative theoretical predictions of redox potentials with standard deviations σ comparable to typical experimental errors of cyclic voltammetry measurements. Agreement for first-, second-, and third-row transition-metal complexes is demonstrated even at a rather modest level of density functional theory (σ = 64 mV for the UB3LYP/6-311G* level). This is shown for a series of benchmark redox couples, including ([MCp2]0/+ (Cp = η5-cyclopentadienyl), [MCp*2]0/+ (Cp* = η5-1,2,3,4,5-pentamethylcyclopentadienyl), [M(bpy)3]2+/3+ (bpy =2,2′-bipyridine), and [Ir(acac)3]0/+ (acac = acetylacetonate), with M = Fe, Co, Ni, Ru, Os, or Ir) in various nonaqueous solvents [acetonitrile (MeCN), dimethyl sulfoxide (DMSO), and dichloromethane (DCM)].

2–6-GHz BiCMOS Polar-Based Vector Modulator for $S$- and $C$-Band Diversity Receivers

This paper presents and analyzes an active vector modulator based on the polar coordinate system and composed of circulator-based phase shifters and a variable gain amplifier. The design provides full phase control range of 360 and gain control range of 36 dB for a wide frequency range of 2-6 GHz. Phase and gain can be controlled with total root mean square (rms) linearity errors of 6.3 and 0.15 dB and rms correlation errors between gain and phase of 0.6 and 1.1 dB, respectively. Therefore, the design is suitable for RF diversity receivers in the - and -bands. The integrated circuit includes all necessary peripheral circuits, such as a digital control block and internal references and covers 1.06 on a 0.25- BiCMOS technology.

JmzIdentML API: A Java interface to the mzIdentML standard for peptide and protein identification data

We present a Java application programming interface (API), jmzIdentML, for the Human Proteome Organisation (HUPO) Proteomics Standards Initiative (PSI) mzIdentML standard for peptide and protein identification data. The API combines the power of Java Architecture of XML Binding (JAXB) and an XPath-based random-access indexer to allow a fast and efficient mapping of extensible markup language (XML) elements to Java objects. The internal references in the mzIdentML files are resolved in an on-demand manner, where the whole file is accessed as a random-access swap file, and only the relevant piece of XMLis selected for mapping to its corresponding Java object. The APIis highly efficient in its memory usage and can handle files of arbitrary sizes. The APIfollows the official release of the mzIdentML (version 1.1) specifications and is available in the public domain under a permissive licence at http://www.code.google.com/p/jmzidentml/.

Exposure of Mycobacteria to Cell Wall-inhibitory Drugs Decreases Production of Arabinoglycerolipid Related to Mycolyl-arabinogalactan-peptidoglycan Metabolism

The "cell wall core" consisting of a mycolyl-arabinogalactan-peptidoglycan (mAGP) complex represents the hallmark of the mycobacterial cell envelope. It has been the focus of intense research at both structural and biosynthetic levels during the past few decades. Because it is essential, mAGP is also regarded as a target for several antitubercular drugs. Herein, we demonstrate that exposure of Mycobacterium bovis Bacille Calmette-Guérin or Mycobacterium marinum to thiacetazone, a second line antitubercular drug, is associated with a severe decrease in the level of a major apolar glycolipid. This inhibition requires MmaA4, a methyltransferase reported to participate in the activation process of thiacetazone. Following purification, this glycolipid was subjected to detailed structural analyses, combining gas-liquid chromatography, mass spectrometry, and nuclear magnetic resonance. This allowed to identify it as a 5-O-mycolyl-β-Araf-(1→2)-5-O-mycolyl-α-Araf-(1→1)-Gro, designated dimycolyl diarabinoglycerol (DMAG). The presence of DMAG was subsequently confirmed in other slow growing pathogenic species, including Mycobacterium tuberculosis. DMAG production was stimulated in the presence of exogenous glycerol. Interestingly, DMAG appears structurally identical to the terminal portion of the mycolylated arabinosyl motif of mAGP, and the metabolic relationship between these two components was provided using antitubercular drugs such as ethambutol or isoniazid known to inhibit the biosynthesis of arabinogalactan or mycolic acid, respectively. Finally, DMAG was identified in the cell wall of M. tuberculosis. This opens the possibility of a potent biological function for DMAG that may be important to mycobacterial pathogenesis.

Referential Verisimilitude, Narrative Necessity and the Poetics of Vision

In Classical Greece, the first forms of historiography sprung from a preoccupation with memory: to memorialize and publicize the actions of men in the recent past. They also aimed to make sense of those actions: the order of human and territorial justice for Herodotus, and the anthropology of domination for Thucydides. In this discursive “shaping” of History, rhetoric played an essential role. It provided an opportunity to muse about modalities of “fiction,” which, etymologically, “makes” hence “fictionalizes” facts, and an opportunity also to think about the importance of verisimilitude in the narrative constructions torn between internal coherence and external references. Hence the oxymoron of “referential fiction.”

Ephemera: The Feeling of Time in Leopardi’s ‘Canto notturno’

In both the Zibaldone and the Operette morali, Leopardi meditates on the subjective perception of the flow of time and represents the intensity of existence with two antithetical models: the bird and the ephemeron. Through an analysis of internal references and external sources, this article attempts to show how the image of the ‘vecchio canuto’ in the ‘Canto notturno’ is intertwined with that of the ephemeron, and to highlight their shared metaphorical value. Moreover, it seeks to interpret the subliminal appearance of the ephemeron alongside the bird in the final stanza of the poem, where the three considerations introduced by ‘forse’ register three precise stages of consciousness, which represent a shift from an inner experience of time to an extra-temporal reality.

Accurate quantification of water–macromolecule exchange induced frequency shift: Effects of reference substance

Water-macromolecule exchange induces a bulk water frequency shift contributing to the contrast in phase imaging. For separating the effects of the water-macromolecule exchange and the macromolecule susceptibility, appropriate internal or external references are needed. In this study, two internal reference compounds, 2,2,3,3-tetradeuterio-3-trimethylsilyl-propionate (TMSP) and 1,4-dioxane, were used to study the macromolecule-dependent water frequency shift in a bovine serum albumin (BSA)-water system in detail. For TMSP, the water-macromolecule exchange shift depended on both the BSA and the reference concentration and stabilized to a value of 0.025 ppm/mM (298 K, TMSP concentrations > 30 mM). For dioxane, the dependency of the water-macromolecule exchange shift on the BSA concentration is independent of dioxane at low concentrations. The resulting shift was smaller (0.009 ppm/mM) when compared with using higher TMSP concentrations as reference. This discrepancy might be due to additional dioxane-water interactions. Measurements with an external chloroform reference in a coaxial geometry showed a shift of -0.013 ppm/mM resulting from the opposing effects of macromolecules in water exchange-induced shift and diamagnetic susceptibility shift. All these effects should be considered in the interpretation of tissue phase contrast. From the experimental data, the equilibrium binding constant between BSA and TMSP has been quantified to be K(d) = 1.3 ± 0.4, and the estimated number of interaction sites for BSA is 12.7 ± 2.6.

Single-Step versus Stepwise Two-Electron Reduction of Polyarylpyridiniums: Insights from the Steric Switching of Redox Potential Compression

Contrary to 4,4'-dipyridinium (i.e., archetypal methyl viologen), which is reduced by two single-electron transfers (stepwise reduction), the 4,1'-dipyridinium isomer (so-called "head-to-tail" isomer) undergoes two electron transfers at apparently the same potential (single-step reduction). A combined theoretical and experimental study has been undertaken to establish that the latter electrochemical behavior, also observed for other polyarylpyridinium electrophores, is due to potential compression originating in a large structural rearrangement. Three series of branched expanded pyridiniums (EPs) were prepared: N-aryl-2,4,6-triphenylpyridiniums (Ar-TP), N-aryl-2,3,4,5,6-pentaphenylpyridiniums (Ar-XP), and N-aryl-3,5-dimethyl-2,4,6-triphenylpyridinium (Ar-DMTP). The intramolecular steric strain was tuned via N-pyridinio aryl group (Ar) phenyl (Ph), 4-pyridyl (Py), and 4-pyridylium (qPy) and their bulky 3,5-dimethyl counterparts, xylyl (Xy), lutidyl (Lu), and lutidylium (qLu), respectively. Ferrocenyl subunits as internal redox references were covalently appended to representative electrophores in order to count the electrons involved in EP-centered reduction processes. Depending on the steric constraint around the N-pyridinio site, the two-electron reduction is single-step (Ar = Ph, Py, qPy) or stepwise (Ar = Xy, Lu, qLu). This steric switching of the potential compression is accurately accounted for by ab initio modeling (Density Functional Theory, DFT) that proposes a mechanism for pyramidalization of the N(pyridinio) atom coupled with reduction. When the hybridization change of this atom is hindered (Ar = Xy, Lu, qLu), the first reduction is a one-electron process. Theory also reveals that the single-step two-electron reduction involves couples of redox isomers (electromers) displaying both the axial geometry of native EPs and the pyramidalized geometry of doubly reduced EPs. This picture is confirmed by a combined UV-vis-NIR spectroelectrochemical and time-dependent DFT study: comparison of in situ spectroelectrochemical data with the calculated electronic transitions makes it possible to both evidence the distortion and identify the predicted electromers, which play decisive roles in the electron-transfer mechanism. Last, this mechanism is further supported by in-depth analysis of the electronic structures of electrophores in their various reduction states (including electromeric forms).

Long-Term Mortality after Recombinant Growth Hormone Treatment for Isolated Growth Hormone Deficiency or Childhood Short Stature: Preliminary Report of the French SAGhE Study

Little is known about the long-term health of subjects treated with GH in childhood, and Safety and Appropriateness of Growth hormone treatments in Europe (SAGhE) is a study addressing this question. The objective of the study was to evaluate the long-term mortality of patients treated with recombinant GH in childhood in France. This was a population-based cohort study. The setting of the study was a French population-based register. A total of 6928 children with idiopathic isolated GH deficiency (n = 5162), neurosecretory dysfunction (n = 534), idiopathic short stature (n = 871), or born short for gestational age (n = 335) who started treatment between 1985 and 1996 participated in the study. Follow-up data on vital status were available in September 2009 for 94.7% of the patients. All-cause and cause-specific mortality was measured in the study. All-cause mortality was increased in treated subjects [standardized mortality ratio (SMR) 1.33, 95% confidence interval (CI) 1.08-1.64]. In a multivariate analysis adjusted for height, the use of GH doses greater than 50 μg/kg · d was associated with mortality rates using external and internal references (SMR 2.94, 95% CI 1.22-7.07, hazard ratio 2.79, 95% CI 1.14-6.82). All type cancer-related mortality was not increased. Bone tumor-related mortality was increased (SMR 5.00, 95% CI 1.01-14.63). An increase in mortality due to diseases of the circulatory system (SMR 3.07, 95% CI 1.40-5.83) or subarachnoid or intracerebral hemorrhage (SMR 6.66, 95% CI 1.79-17.05) was observed. Mortality rates were increased in this population of adults treated as children with recombinant GH, particularly in those who had received the highest doses. Specific effects were detected in terms of death due to bone tumors or cerebral hemorrhage but not for all cancers. These results highlight the need for additional studies of long-term mortality and morbidity after GH treatment in childhood.

Manuel De Droit Canonique (review)

Reviewed by: Manuel De Droit Canonique Anne Asselin, Dean Manuel De Droit Canonique by Dominique Le Tourneau. Montréal: Wilson et Lafleur, Collection Gratianus, 2010. To the seven chapters commenting on the books of the Code of Canon Law, the author has added a first chapter outlining a brief history of canon law and a closing chapter on public ecclesiastical law and civil ecclesiastical law. The introduction lays out the general principles of law and justice, of natural law, of human rights, and finally of canon law. In each chapter, the author provides a useful bibliography, although limited to French books and articles. Paragraphs are numbered, allowing for easy internal references. The book is written in a clear and non-pretentious style, with occasional humorous interjections, making it a work that is accessible to non-canonists as well as canonists looking for a general overview of the Code. The use of [End Page 300] titles and sub-titles draws the reader's attention to the core of the canon or canons of a particular section. References to the Eastern Code are meticulously added whenever required. In fact, the author has added sections, which, although pertaining to the Eastern Churches, are judged essential to a proper canonical understanding and overview of the law. For example, while commenting on Book II of the Latin Code, he adds an entire section on patriarchal churches, the powers, rights and obligations of the patriarch, and major archiepiscopal churches. What is especially helpful is the author's generous use of examples to comment on a particular canon: for example, to explain a contra legem custom, references to canons explicitly mentioning reprobation of a custom are listed, both in the Latin and the Eastern Codes. The handbook goes beyond the mere commentary of a particular canon, often adding theological underpinnings or more recent papal pronouncements expounding legislative texts. When necessary, references to particular law are added, for example, when referring to the age for receiving the sacrament of confirmation or conditions under which general absolution may be allowed. The commentary on Book II, the People of God, is the most voluminous, providing a more detailed instruction on the rights and obligations of the faithful pertaining to the conditio communionis, the conditio libertatis, the conditio activa, and the conditio subiectionis. The commentaries on Books V and VI are perhaps the shortest, but they do still contain the basic information and solid footing required by anyone seeking to make heads or tails of these oft confused or misused sections of the Code. Further readings would be required, however, of anyone having to apply the canons to particular cases. This book fills a definite void. There is a sad paucity of French canonical works. The Manuel de droit canonique will be a useful tool for students as a good overview of the canons of the Code, for canonists requiring a brief refresher on one section or another, and for non-canonists wishing to acquire a basic but solid knowledge of canon law. [End Page 301] Anne Asselin, Dean Faculty of Canon Law Saint Paul University Copyright © 2012 The Catholic University of America Press

“Prolific in Expression and Broad in Thought”: Internal References to Philo’s Allegorical Commentary and Exposition of the Law

Philo of Alexandria wrote three major commentaries on the Pentateuch. The relationship of these has been a matter of continuing debate. This essay attempts to clarify the relationship between Philo...

Il sogno raccontato nel Filocolo di Giovanni Boccaccio

The goal of this contribution is to isolate the narrative microtexts referred to dream or sight in such an emblematic work as Il Filocolo, the first great novel by Giovanni Boccaccio, by going into a deep analysis of some aspects like the spatial and temporal situation of the narrative time of the microtext and their subsequent interpretation in the macrotext. On the other hand, it will also be intended to show that the recurrent usage of this kind of microstories is one of the narrative resources used by Boccaccio for upgrading in literary terms the advance of such a long and complex novel; and, thus, it would be convenient to pay attention to the great game of internal references established between the oniric microtexts and the storytelling as a whole.

The emerging epidemic of estrogen‐related cancers in young women in a developing Asian country

The incidence of breast and genital tract cancers is increasing among Taiwanese women, but the age specificity and histopathological features of these cancers have not been determined. We used a descriptive epidemiological method and data from the Taiwan Cancer Registry (1979-2007) to examine secular trends in the age-specific incidences of female breast cancer, three major female genital tract cancers and the histopathological subtypes of these cancers. Age-specific incidence rates in the United States (1978-2002) were used as an external reference, and the incidence rates of all malignancies and of malignant brain tumors were used as internal references. We found that age-adjusted incidence rates of female breast, uterine, and ovarian cancers increased in Taiwan from 1979 to 2007, whereas the incidence of cervical cancer decreased after 1998. The largest increase was observed for ductal and lobular carcinomas of the breast and endometrioid carcinomas of the uterus and ovary in women ≤55 years, all of these tumors show a high prevalence of hormone receptor expressions. In addition, hormone-receptor-positive rates of breast cancer were uniquely higher in younger, as opposed to older, Taiwanese women. These findings indicate that estrogen-related cancers rapidly emerge in young women in Taiwan and that incidence rates are catching up with that of women living in the United States.

Sensitivity of MRD Detection in AML: qPCR Vs. MFC - a Plethora to Choose From, but Which Is Best?

Abstract 1447 Background:There is a growing realization that outcome of acute myeloid leukemia (AML) is strongly correlated to whether minimal residual disease (MRD) - as quantified by either multicolor flow cytometry (MFC) or real-time quantitative polymerase chain reaction (qPCR) - is demonstrable at crucial clinical decision time points. While FCM is applicable in up to 95% of all cases through the detection of leukemia-associated immunophenotypes (LAIPs), its major drawback is the lack of sensitivity in most cases and antigen shift, which is seen in up to 20% of cases. In contrast, while its sensitivity is generally considered to be higher than that of FCM, qPCR can only be applied in less than 80% of the patients. We have previously reported human Myeloid Inhibitory C-type Lectin (hMICL) and the interleukin-3 receptor alpha (CD123) to be potent and widely applicable markers in MRD detection by MFC, but the sensitivity of this approach compared to qPCR techniques remains to be elucidated (Clinical Cytometry, Part B, in press). Problem formulation: No previous studies have to our knowledge established the sensitivity levels of markers within these methodologies. Data from such experimentation would allow for better decision making as to what marker to apply in the given patient. Hypothesis: We hypothesized that the direct comparison between MRD technologies might yield hard data as to optimal choice of methods in the pre-clinical setting, and ultimately also for design of future FCM based MRD protocols. Results: Initially, we determined the validity of hMICL/CD123 FCM assay by performing two-fold dilution series of cryopreserved AML cells in highly purified T-cells, the latter being hMICL-/CD123-/CD34-/CD117-. Dilutions at 1: 1 to 1: 214 displayed linearity in MRD drop and resulted in a coefficient of correlation of 0.99 (P = <0.01) for all experiments. The sensitivity was calculated from the plateau-phase at of the titration curve at 1: 216 and reached a maximal sensitivity of 1: 30.000 in this setting. In order to evaluate the sensitivity of the hMICL/CD123 technique compared to standard qPCR methods in experiments, we admixed leukemic blasts from 5 patients with either known fusion transcript positive and WT-1 + disease in normal bone marrow. Sensitivities were calculated from the plateau phase at 216. The most sensitive LAIP was defined in each patient from internal standard references generated from normal donors and regenerating BM from acute lymphoblastic leukemia patients. The detection limits of MFC ranged from 10−3 to below 10−4 for the most sensitive hMICL/CD123 combinations. While the fusion transcript qPCR assays were found to be the most sensitive, the hMICL/CD123 FCM one stood up surprisingly well in 3 of 5 cases of fusion transcript positive disease and approached the qPCR assay. In all 5 cases the FCM did better than the WT1-assay (an example of titration curves and relative MRD values for a PML-RARA + patient is given in the Figure). In the clinical setting, we analyzed a total of 69 unselected AML patients consecutively diagnosed at our department. A total of 10 different hMICL/CD123 LAIPs were analyzed closely, of which one or more were present in 90% of the patients. By calculating log differences between diagnostic AML samples and normal and regenerating BM we found the frequency of LAIP+ cells to be more than 4 logs higher in leukemia than in normal BM for the most sensitive combinations of LAIPs. Conclusion: These data are the first to directly compare MRD sensitivity of FCM and qPCR in spiking experiments and in a larger patient material. They reveal that a new assay involving hMICL and CD123, which are stable markers throughout the disease in these patients, has a surprisingly high sensitivity, though not quite at the level of standard qPCR assays. These data can be used for the design of future studies of cytoreduction in AML, where individualized therapy is warranted. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

The role of infant feeding practices in the explanation for ethnic differences in infant growth: the Amsterdam Born Children and their Development study

Rapid early growth in infants may influence overweight and CVD in later life. Both rapid growth and these disease outcomes disproportionately affect some ethnic minorities. We determined ethnic differences in growth rate (Δ standard deviation scores, ΔSDS) during the first 6 months of life and assessed the explanatory role of infant feeding. Data were derived from a multiethnic cohort for the Amsterdam Born Children and their Development study (The Netherlands). Growth data (weight and length) of 2998 term-born singleton infants with no fetal growth restriction were available for five ethnic populations: Dutch (n 1619), African descent (n 174), Turkish (n 167), Moroccan (n 232) and other non-Dutch (n 806). ΔSDS for weight, length and weight-for-length between 4 weeks and 6 months were defined using internal references. Infant feeding pattern (breast-feeding duration, introduction of formula feeding and complementary feeding) in relation to ethnic differences in growth rate was examined by multivariate linear regression. Results showed that the growth rate was higher in almost all ethnic minorities, with β between 0·07 and 0·41 for ΔSDS weight and between 0·12 and 0·42 for ΔSDS length, compared with ethnic Dutch infants. ΔSDS weight-for-length was similar across groups, except for Moroccan infants (β 0·25, P<0·05) after correction for confounders. In general, exclusive breast-feeding for 4 months was associated with slower growth for all three growth measures. Feeding factors explained, to a small degree, the higher weight and length gain in African descent infants, but not the higher ΔSDS weight-for-length in the Moroccan population. More research is needed to elucidate the underlying mechanisms of the high infant growth rate in Turkish and Moroccan infants.

Image orientation for three-dimensional echocardiography of congenital heart disease

To date there has been little discussion about image orientation for three-dimensional (3D) echocardiography when applied to congenital heart lesions. Anatomic relations cannot be assumed in congenital heart disease and image cropping during post processing may by necessity remove external or even internal anatomic references. We present an approach to consistent anatomic orientation which is both intuitive and consistent with regard to superior-inferior, anterior-posterior and left-right axes. Such anatomic orientation is also concordant with other common 3D imaging modes such as cardiac magnetic resonance imaging and computed tomography. Views derived from standard cross sectional echocardiography have such universal familiarity that analogous 3D projections of these views may be retained but novel hitherto unavailable views such as en face views of the cardiac septums or atrioventricular valves may be projected using anatomic orientation.