Measurement is the foundation of research and theory on children's eating behaviours: Current issues and directions for progress.

Eating behaviours affect food intakes and are involved in the aetiology of obesity. There has been impetus to translate findings about children's eating behaviour into intervention and policy programs. However, measurement limitations have hindered our capacity to understand and influence children's eating behaviours. In the present paper we provide an overview of some of the key methodological and measurement issues facing the field of children's eating behaviours and highlight implications for research and health promotion. Drawing on insight from parallel issues that occur in the measurement of early social and emotional development, we examine two overlapping themes in children's (aged 0-∼12 years) eating behaviours (1) measurement issues related to validity and reliability, and (2) associated methodological challenges, such as contextual influences and the importance of designing studies that use multiple informants and multiple methods. We then suggest insights and strategies aimed at advancing approaches to measurement of children's eating behaviours. To progress our understanding of children's eating behaviours, we conclude that a range of psychometrically sound, fit-for-purpose measurement instruments and procedures are needed for use in multi-trait, multi-method, multi-informant studies in a range of populations and contexts.

Tunable broadband terahertz polarizer using graphene-metal hybrid metasurface.

We demonstrate an electrically tunable polarizer for terahertz (THz) frequency electromagnetic waves formed from a hybrid graphene-metal metasurface. Broadband (>3 THz) polarization-dependent modulation of THz transmission is demonstrated as a function of the graphene conductivity for various wire grid geometries, each tuned by gating using an overlaid ion gel. We show a strong enhancement of modulation (up to ∼17 times) compared to graphene wire grids in the frequency range of 0.2-2.5 THz upon introduction of the metallic elements. Theoretical calculations, considering both plasmonic coupling and Drude absorption, are in good agreement with our experimental findings.

Increasing the sensitivity of terahertz split ring resonator metamaterials for dielectric sensing by localized substrate etching.

We demonstrate a significant enhancement in the sensitivity of split ring resonator terahertz metamaterial dielectric sensors by the introduction of etched trenches into their inductive-capacitive gap area, both through finite element simulations and in experiments performed using terahertz time-domain spectroscopy. The enhanced sensitivity is demonstrated by observation of an increased frequency shift in response to overlaid dielectric material of thicknesses up to 18 µm deposited on to the sensor surface. We show that sensitivity to the dielectric is enhanced by a factor of up to ∼2.7 times by the incorporation of locally etched trenches with a depth of ∼3.4 µm, for example, and discuss the effect of the etching on the electrical properties of the sensors. Our experimental findings are in good agreement with simulations of the sensors obtained using finite element methods.

No association between rate of torque development and onset of muscle activity with increased risk of hamstring injury in elite football.

Hamstring injuries remain a significant burden in sports that involve high-speed running. In elite male football, hamstring injury has repeatedly been identified as the most common non-contact injury, representing 12% of all injuries. As the incidence remains high, investigations are aimed at better understanding how to improve prevention efforts. Intrinsic risk factors such as strength have been investigated extensively in a cohort of professional football players; however, other intrinsic measures of neuromuscular function have not been studied in this cohort. This study aims to investigate the association between timing of hamstring muscle activity onset and the rate of torque development during the early phase of isokinetic strength testing with risk of hamstring injury in professional football players in a prospective cohort study. All teams (n = 18) eligible to compete in the premier football league in Qatar underwent a comprehensive strength assessment during their annual periodic health evaluation at Aspetar Orthopaedic and Sports Medicine Hospital in Doha, Qatar. Variables included rate of torque development and timing of muscle activity onset. A total of 367 unique players (60.6% of all QSL players) competed for 514 player seasons (103 players competed both seasons) and sustained 65 hamstring injuries. There was no difference in the onset of muscle activity between the biceps femoris and medial hamstrings comparing the injured to uninjured players. For both onset of muscle activity and rate of torque development, there were no significant differences between any of the variables (P > .05), with small effect sizes detected across all the different variables (d < 0.3). Rate of torque development and onset of muscle activity were not associated with a risk of future hamstring injury. The use of these measures as part of a periodic health evaluation to identify risk of hamstring injury is unsupported.

The Adrenocortical Response to Synthetic ACTH Following a Trek to High Altitude.

Gradual ascent to high altitude is typically associated with reduced resting aldosterone and unchanged cortisol, features that may facilitate acclimatization but are poorly understood. The aim of the study was to investigate the cortisol and aldosterone response to adrenocorticotrophic hormone at altitude. Eleven subjects underwent a 250 µg short synacthen test at sea-level and again after trekking to 3 600 m in Nepal. Cortisol and aldosterone were measured by conventional assay from blood samples taken immediately prior to the administration of synacthen (T0) and then 30 (T30) and 60 (T60) min later. At 3 600 m resting basal cortisol and aldosterone levels were both significantly lower than they were at sea-level (p=0.004, p=0.003, respectively). Cortisol values at T30 and T60 were not different between sea-level and 3 600 m but the increment after synacthen was significantly greater (p=0.041) at 3 600 m due to a lower basal value. Aldosterone at T30 and T60 was significantly lower (p=0.003 for both) at 3 600 m than at sea-level and the increment following synacthen was also significantly less (p=0.003) at 3 600 m. At 3 600 m there appears to be a divergent adrenal response to synthetic adrenocorticotrophic hormone with an intact cortisol response but a reduced aldosterone response, relative to sea-level. This may reflect a specific effect of hypoxia on aldosterone synthesis and may be beneficial to acclimatization.

Rural vs. urban disparities in association with lower urinary tract symptoms and benign prostatic hyperplasia in ageing men, NHANES 2001-2008.

OBJECTIVE: The objective of this study was to investigate rural/urban and socio-demographic disparities in lower urinary tract symptoms and benign prostatic hyperplasia (LUTS/BPH) in a nationally representative population of men. METHODS: Data on men age ≥40 years (N = 4,492) in the 2001-2008 National Health and Nutrition Examination Surveys were analysed. Self-report of physician-diagnosed enlarged prostate and/or BPH medication use defined recognised LUTS/BPH. Urinary symptoms without BPH diagnosis/medications defined unrecognised LUTS/BPH. Rural-Urban Commuting Area Codes assessed urbanisation. Unadjusted and multivariable associations (odds ratios (OR)) between LUTS/BPH and covariates were calculated using logistic regression. RESULTS: Recognised and unrecognised LUTS/BPH weighted-prevalence estimates were 16.5% and 9.6%. There were no significant associations between LUTS/BPH and rural/urban status. Significant predisposing factors for increased adjusted odds of recognised and unrecognised LUTS/BPH included age, hypertension (OR=1.4;1.4), analgesic use (OR=1.4;1.4) and PSA level >4 ng/mL (OR=2.3;1.9) when adjusted for rural/urban status, race, education, income, alcohol, health insurance, health care and proton pump inhibitor (PPI) use (all p ≤ 0.1). Restricting to urban men only (N = 3,371), healthcare use (≥4visits/year) and PPI's increased adjusted odds of recognised LUTS/BPH (OR=2.0;1.6); no health insurance and

Copeptin and arginine vasopressin at high altitude: relationship to plasma osmolality and perceived exertion.

PURPOSE: A diuresis is a key part of acclimatisation to high altitude (HA). Arginine vasopressin (AVP) is a hormone involved in salt and water balance and may potentially have a role in the development of altitude illness. ProAVP (copeptin) is more stable than AVP and is assayed by a straightforward, automated method. We investigated the relationship of AVP to copeptin and the copeptin response to exercise and altitude illness in a large cohort during a field study at HA. METHODS: 48 subjects took part in a 10-day trek at HA. Venous blood samples were taken at 3,833, 4,450 and 5,129 m post-trek (exercise) and the following day at rest. Daily recordings of symptoms of altitude illness, oxygen saturations and perceived exertion were carried out. RESULTS: AVP and copeptin levels increased with exercise and correlated closely (ρ 0.621 p < 0.001), this was strongest in the stressed state when AVP secretion was highest, at 5,129 m post-exercise (ρ 0.834 p < 0.001). On two-way ANOVA, both altitude (F = 3.5; p = 0.015) and exercise (F = 10.2; p = 0.002) influenced copeptin levels (interaction F = 2.2; p = 0.08). AVP levels were influenced by exercise (F = 14.4; p = 0.0002) but not altitude (F = 2.0; p = 0.12) with no overall group interactions (F = 1.92.6; p = 0.06). There was no association between copeptin or arginine vasopressin and altitude illness. Copeptin correlated with the Borg RPE score and was significantly higher in the group with a Borg score ≥15 (7.9 vs. 3.7 p < 0.001). CONCLUSION: We have shown that arginine vasopressin and copeptin levels correlate and are suppressed below 5,129 m. Furthermore, we have demonstrated that exertion, rather than altitude illness or increasing osmolality, is the stimulus for increases in copeptin.

Influence of Trifloxystrobin on Primary Inoculum and Progression of Scab Epidemics on Stone Fruit.

The ability of the QoI fungicide trifloxystrobin to reduce production of conidia by Fusicladium carpophilum on twig lesions was quantitatively assessed over a 3-year period from 2005 through 2007. Four annual treatment programs, consisting of two consecutive trifloxystrobin applications at pink + bloom, bloom + petal fall, and petal fall + shuck-split, plus a single application timing at petal fall, were examined in a 'Redgold' nectarine orchard harboring high levels of overwintering scab lesions. Sporulation potential, the ability of twig lesions to produce conidia under optimum environmental conditions, was subsequently assessed five to six times during each spring and early summer. In each year of the study, all four treatments significantly reduced the area under the sporulation curve or peak sporulation. The petal fall + shuck-split program provided the greatest antisporulant activity, reducing conidia production at peak sporulation by 82 to 92%. Furthermore, examination of results over the 3-year period showed that the programs significantly slowed the annual rate of increase in peak sporulation; however, none of the programs completely halted or caused a decline in the annual rate. Although no fungicide was applied after the treatment programs, results from fruit disease assessments showed that these programs, applied as much as 3 months earlier, significantly reduced disease incidence and, in particular, disease severity. A comparison of four QoI fungicides in 2008 indicated that trifloxystrobin and azoxystrobin provided the most control of fruit scab, while pyraclostrobin + boscalid and fluoxastrobin yielded minimal or no benefit. Results of this study demonstrate that certain QoI fungicides, in particular trifloxystrobin and azoxystrobin, can probably improve the efficacy of current protectant programs used for peach scab control by providing season-long control of F. carpophilum sporulation on twig lesions. Such program enhancement may be critical when orchards have high inoculum levels and/or environmental conditions are very favorable to disease development.

Investigation of the Blood Glucose Lowering Potential of the Jamaican Momordica charantia (Cerasee) Fruit in Sprague-Dawley Rats.

The Momordica charantia (MC) fruit has been documented to possess antidiabetic properties. However, these studies were not without controversy surrounding the blood glucose-lowering ability and the mechanism of action in diabetes therapy. In an effort to evaluate such claims in the Jamaican MC species known as cerasee, aqueous extracts of the unripe fruit were studied in normal and diabetic rats. Normal male Sprague-Dawley rats were divided into groups (n = 6) orally administered distilled water, 10% dimethyl sulfoxide (DMSO) solution, the aqueous extract (400 mg/kg body weight) and glibenclamide (15 mg/kg body weight), respectively prior to assessment of fasting blood glucose (FBG) concentration. The oral glucose tolerance test (OGTT) was conducted in normoglycaemic rats orally administered distilled water, 10% DMSO solution, glibenclamide (15 mg/kg body weight) or aqueous extracts of the fruit (200 and 400 mg/kg body weight). Blood glucose concentration was also monitored in streptozotocin-induced diabetic rats administered the aqueous extract (250 mg/kg body weight) or water vehicle after an overnight fast. The aqueous extracts showed no hypoglycaemic or antidiabetic activity. However, the administration of the aqueous extracts (200 and 400 mg/kg body weight) resulted in significant improvement in glucose tolerance of glucose-primed normoglycaemic rats during the OGTT. These data suggest that the glucose-lowering mechanism of the Jamaican MC fruit species likely involves altered glucose absorption across the gastrointestinal tract.

Extremely preterm birth and adolescent mental health in a geographical cohort born in the 1990s.

BACKGROUND: Preterm birth confers risk for poor outcome, including mental health problems. Survival of extremely preterm (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g) infants increased in the 1990s but psychiatric outcomes in older adolescents born preterm since 1990 are not well documented. This study aimed to characterize mental health and personality traits in a prospective geographical cohort of adolescents born EP/ELBW in Victoria, Australia in 1991 and 1992. METHOD: At age 18 years, 215 EP/ELBW and 157 normal birthweight (>2499 g) control adolescents completed the Structured Clinical Interview for DSM-IV Disorders, Axis 1 Non-Patient version (SCID-I/NP), the Children's Interview for Psychiatric Syndromes (ChIPS) attention deficit hyperactivity disorder (ADHD) module, and questionnaires assessing recent depression and anxiety symptoms and personality traits. RESULTS: ADHD prevalence was significantly elevated in EP/ELBW adolescents compared with controls [15% v. 7%; odds ratio (OR) 2.67, 95% confidence interval (CI) 1.08-6.58]. Aside from ADHD, however, EP/ELBW and control adolescents reported very similar outcomes, with other lifetime diagnoses identified in 23% of EP/ELBW and 21% of controls. These were predominantly mood and anxiety disorders (21% EP/ELBW, 20% controls). The groups did not differ in recent depression or anxiety symptoms assessed using questionnaires, and personality traits were also similar. CONCLUSIONS: ADHD was more prevalent in EP/ELBW adolescents than controls, which is consistent with some, but not all, reports on preterm survivors born before the 1990s, and younger preterm children born in the 1990s. The high rates of anxiety and mood disorders were similar in both groups, and comparable with population-based estimates.

How Long Does Contouring Really Take? Results of the Royal College of Radiologists Contouring Surveys.

AIMS: The success and safety of modern radiotherapy relies on accurate contouring. Understanding the time taken to complete radiotherapy contours is critical to informing workforce planning and, in the context of a workforce shortfall, advocating for investment in technology and multi-professional skills mix. We aimed to quantify the time taken to delineate target volumes for radical radiotherapy. MATERIALS AND METHODS: The Royal College of Radiologists circulated two electronic surveys via email to all clinical oncology consultants in the UK. The individual case survey requested anonymous data regarding the next five patients contoured for radical radiotherapy. The second survey collected data on respondents' usual practice in radiotherapy contouring. RESULTS: The median time to contour one radiotherapy case was 85 minutes (IQR = 50-131 minutes). Marked variability between and within tumour sites was evident: paediatric cancers took the most time (median = 210 minutes, IQR = 87.5 minutes), followed by head and neck and gynaecological cancers (median = 120 minutes, IQR = 71 and 72.5 minutes respectively). Breast cancer contouring required the least time (median = 43 minutes, IQR = 60 minutes). Radiotherapy technique, inclusion of nodes and 4D CT planning were associated with longer contouring times. A non-medical professional was involved in contouring in 65% of cases, but clinical oncology consultants were involved in target volume delineation in 90% of cases, and OARs in 74%. Peer review took place in 46% of cases with 56% of consultants reporting no time for peer review in their job plan. CONCLUSION: Contouring for radical radiotherapy is complex and time-consuming, and despite increasing involvement of non-medical professionals, clinical oncology consultants remain the primary practitioners. Peer review practice is variable and time is often a limiting factor. Many factors influence the time required for contouring, and departments should take these factors and the need for peer-review into account when developing job plans.

The assessment of vascular risk in men with erectile dysfunction: the role of the cardiologist and general physician.

Erectile dysfunction (ED) and cardiovascular disease (CVD) share risk factors and frequently coexist, with endothelial dysfunction believed to be the pathophysiologic link. ED is common, affecting more than 70% of men with known CVD. In addition, clinical studies have demonstrated that ED in men with no known CVD often precedes a CVD event by 2-5 years. ED severity has been correlated with increasing plaque burden in patients with coronary artery disease. ED is an independent marker of increased CVD risk including all-cause and especially CVD mortality, particularly in men aged 30-60 years. Thus, ED identifies a window of opportunity for CVD risk mitigation. We recommend that a thorough history, physical exam (including visceral adiposity), assessment of ED severity and duration and evaluation including fasting plasma glucose, lipids, resting electrocardiogram, family history, lifestyle factors, serum creatinine (estimated glomerular filtration rate) and albumin:creatinine ratio, and determination of the presence or absence of the metabolic syndrome be performed to characterise cardiovascular risk in all men with ED. Assessment of testosterone levels should also be considered and biomarkers may help to further quantify risk, even though their roles in development of CVD have not been firmly established. Finally, we recommend that a question about ED be included in assessment of CVD risk in all men and be added to CVD risk assessment guidelines.

Modeling sporulation of Fusicladium carpophilum on nectarine twig lesions: relative humidity and temperature effects.

The production of conidia by Fusicladium carpophilum on twig lesions was quantitatively modeled as a function of temperature and duration of high relative humidity. During peak sporulation periods in 2007, 2008, and 2009, 1-year-old twigs bearing abundant overwintering lesions were removed from a heavily infected 'Redgold' nectarine orchard, placed in trays at high relative humidity (>95%), and incubated at eight constant temperatures for seven durations, resulting in a factorial design of 56 treatment combinations. Conidia numbers were estimated with a hemacytometer. Results from a six-stage modeling process indicated that, at any given temperature, spore production during high relative humidity periods increased in a monomolecular- to Gompertz-like pattern. The Richards model, with shape parameters of 0.79 to 0.90, was found to provide the best overall fit. When the asymptote and rate parameters were derived as functions of temperature using Gaussian and quadratic models, respectively, the duration of high relative humidity and temperature described 90 to 94% of the variation in conidia production. Predictions of the final models were highly correlated with observed levels of sporulation (r > 0.94; P < 0.0001), indicating an excellent fit to the data. The optimum temperature for sporulation, based on fitting a Gaussian model to the maximum sporulation levels at each temperature, was 17.9 to 20.2°C, with an overall average of 18.8°C. The derived models give a quantitative description of sporulation by F. carpophilum and may have potential use in simulators and forecasting systems.

Prevalence of psychiatric diagnoses in preterm and full-term children, adolescents and young adults: a meta-analysis.

BACKGROUND: Preterm (PT) birth and low birth weight (LBW) are high-prevalence events that are associated with adverse outcomes in the longer term, with vulnerability increasing as maturity at birth decreases. Psychiatric symptomatology appears heightened in PT/LBW survivors, though there are some discordant findings from studies using questionnaire measures, particularly with respect to anxiety and depressive symptoms. METHOD: This article synthesises findings from research using clinical psychiatric diagnostic criteria in PT/LBW individuals aged 10-25 years compared with term-born peers. Key outcomes of interest were the rates of individuals receiving any psychiatric diagnosis and the number of diagnoses of anxiety or depressive disorders. RESULTS: A literature search for studies reporting prevalence of 'any diagnosis' yielded five studies that met inclusion criteria, with a total of 565 PT/LBW and 533 control individuals. Also, five studies were found that reported rates of anxiety/depression (692 PT/LBW and 605 control individuals). The risk of these outcomes was increased for PT/LBW individuals compared with controls [any diagnosis: odds ratio (OR) 3.66, 95% confidence interval (CI) 2.57-5.21; anxiety or depressive disorder: OR 2.86, 95% CI 1.73-4.73]. CONCLUSIONS: The studies reviewed here indicate that, in addition to monitoring and management of medical and cognitive sequelae, the psychological well-being of PT/LBW individuals should be a key part of ongoing care.

Ejaculatory abnormalities in mice with targeted disruption of the gene for heme oxygenase-2.

Nitric oxide (NO) is well established as a neurotransmitter in the central and peripheral nervous systems. More recently, another gas, carbon monoxide (CO) has also been implicated in neurotransmission. In the nervous system CO is formed by a subtype of heme oxygenase (HO) designated HO2. HO2 is localized to discrete neuronal populations in the brain resembling localizations of soluble guanylyl cyclase, which is activated by CO. CO may also function in the peripheral autonomic nervous system, in conjunction with NO. The majority of ganglia in the myenteric plexus possess both HO2 and neuronal NO synthase (NOS). Defects in myenteric plexus neurotransmission occur both in mice with targeted deletion of genes for HO2 and neuronal NOS. HO2 also occurs in other autonomic ganglia including the petrosal, superior cervical and nodose ganglia. Neuronal NOS is localized to neurons regulating male reproductive behavior, such as penile erection, and NOS inhibitors prevent erection. Because of the other parallels between NO and CO, we speculated that CO may play a role in male reproductive behavior. In the present study we describe HO2 localization in neuronal structures regulating copulatory reflexes. Reflex activity of the bulbospongiosus muscle, which mediates ejaculation and ejaculatory behavior, is markedly diminished in mice with targeted deletion of the gene for HO2 (HO2-).

Urinary bladder-urethral sphincter dysfunction in mice with targeted disruption of neuronal nitric oxide synthase models idiopathic voiding disorders in humans.

Idiopathic voiding disorders affect up to 10-15% of men and women. We describe bladder abnormalities in mice with targeted deletion of the gene for neuronal nitric oxide synthase which model the clinical disorders. The mice possess hypertrophic dilated bladders and dysfunctional urinary outlets which do not relax in response to electrical field stimulation or L-arginine. The mice also display increased urinary frequency.

Measurement and analysis of the diffuse reflectance of powdered samples at terahertz frequencies using a quantum cascade laser.

We report terahertz (THz) diffuse reflectance measurements of bulk powdered samples at a frequency of 2.83 THz using a narrowband quantum cascade laser. Samples studied comprise polydisperse powders with absorption coefficients extending over two orders of magnitude from ∼3 cm(-1) to >200 cm(-1). Diffuse reflectance measurements are used to obtain the effective absorption coefficient of these samples from the backscattering cross-section, predicted under the quasi-crystalline approximation (QCA) in the T-matrix formulation and in conjunction with the Percus-Yevick pair distribution function. Results are compared with effective absorption coefficients obtained from THz time-domain spectroscopy measurements on pressed pellet samples, and show good agreement over the range of effective absorption coefficients studied. We observe that the backscattering cross-section predicted under the QCA is strongly dependent on both the real and imaginary components of the complex permittivity of the sample, and we show that reliable determination of the absorption coefficient from diffuse reflectance measurements therefore requires knowledge of the sample's refractive index. This work demonstrates the applicability of diffuse reflectance measurements, using a THz frequency quantum cascade laser, to the high-resolution spectroscopic analysis of bulk powdered samples at THz frequencies.

Imageability and body-object interaction ratings for 599 multisyllabic nouns.

We collected imageability and body-object interaction (BOI) ratings for 599 multisyllabic nouns. We then examined the effects of these variables on a subset of these items in picture-naming, word-naming, lexical decision, and semantic categorization. Picture-naming latencies were taken from the International Picture-Naming Project database (Szekely, Jacobsen, D'Amico, Devescovi, Andonova, Herron, et al. Journal of Memory and Language, 51, 247-250, 2004), word-naming and lexical decision latencies were taken from the English Lexicon Project database (Balota, Yap, Cortese, Hutchison, Kessler, Loftis, et al. Behavior Research Methods, 39, 445-459, 2007), and we collected semantic categorization latencies. Results from hierarchical multiple regression analyses showed that imageability and BOI separately accounted for unique latency variability in each task, even with several other predictor variables (e.g., print frequency, number of syllables and morphemes, age of acquisition) entered first in the analyses. These ratings should be useful to researchers interested in manipulating or controlling for the effects of imageability and BOI for multisyllabic stimuli in lexical and semantic tasks.

Mutant N-RAS induces erythroid lineage dysplasia in human CD34+ cells.

RAS mutations arise at high frequency (20-40%) in both acute myeloid leukemia and myelodysplastic syndrome (which is considered to be a manifestation of preleukemic disease). In each case, mutations arise predominantly at the N-RAS locus. These observations suggest a fundamental role for this oncogene in leukemogenesis. However, despite its obvious significance, little is known of how this key oncogene may subvert the process of hematopoiesis in human cells. Using CD34+ progenitor cells, we have modeled the preleukemic state by infecting these cells with amphotropic retrovirus expressing mutant N-RAS together with the selectable marker gene lacZ. Expression of the lacZ gene product, beta-galactosidase, allows direct identification and study of N-RAS-expressing cells by incubating infected cultures with a fluorogenic substrate for beta-galactosidase, which gives rise to a fluorescent signal within the infected cells. By using multiparameter flow cytometry, we have studied the ability of CD34+ cells expressing mutant N-RAS to undergo erythroid differentiation induced by erythropoietin. By this means, we have found that erythroid progenitor cells expressing mutant N-RAS exhibit a proliferative defect resulting in an increased cell doubling time and a decrease in the proportion of cells in S + G2M phase of the cell cycle. This is linked to a slowing in the rate of differentiation as determined by comparative cell-surface marker analysis and ultimate failure of the differentiation program at the late-erythroblast stage of development. The dyserythropoiesis was also linked to an increased tendency of the RAS-expressing cells to undergo programmed cell death during their differentiation program. This erythroid lineage dysplasia recapitulates one of the most common features of myelodysplastic syndrome, and for the first time provides a causative link between mutational activation of N-RAS and the pathogenesis of preleukemia.