Detection of the PAX3-FKHR fusion gene in paediatric rhabdomyosarcoma: a reproducible predictor of outcome?

Rhabdomyosarcoma has 2 major histological subtypes, embryonal and alveolar. Alveolar histology is associated with the fusion genes PAX3-FKHR and PAX7-FKHR. Definition of alveolar has been complicated by changes in terminology and subjectivity. It is currently unclear whether adverse clinical behaviour is better predicted by the presence of these fusion genes or by alveolar histology. We have determined the presence of the PAX3/7-FKHR fusion genes in 91 primary rhabdomyosarcoma tumours using a combination of classical cytogenetics, FISH and RT-PCR, with a view to determining the clinical characteristics of tumours with and without the characteristic translocations. There were 37 patients with t(2;13)/PAX3-FKHR, 8 with t(1;13) PAX7-FKHR and 46 with neither translocation. One or other of the characteristic translocations was found in 31/38 (82%) of alveolar cases. Univariate survival analysis revealed the presence of the translocation t(2;13)/PAX3-FKHR to be an adverse prognostic factor. With the difficulties in morphological diagnosis of alveolar rhabdomyosarcoma on increasingly used small needle biopsy specimens, these data suggest that molecular analysis for PAX3-FKHR will be a clinically useful tool in treatment stratification in the future. This hypothesis requires testing in a prospective study. Variant t(1;13)/PAX7-FKHR appears biologically different, occurring in younger patients with more localised disease. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Phytotoxic Effects of (±)-Catechin In vitro, in Soil, and in the Field

BACKGROUND: Exploring the residence time of allelochemicals released by plants into different soils, episodic exposure of plants to allelochemicals, and the effects of allelochemicals in the field has the potential to improve our understanding of interactions among plants. METHODOLOGY/PRINCIPAL FINDINGS: We conducted experiments in India and the USA to understand the dynamics of soil concentrations and phytotoxicity of (+/-)-catechin, an allelopathic compound exuded from the roots of Centaurea maculosa, to other plants in vitro and in soil. Experiments with single and pulsed applications into soil were conducted in the field. Experimental application of (+/-)-catechin to soils always resulted in concentrations that were far lower than the amounts added but within the range of reported natural soil concentrations. Pulses replenished (+/-)-catechin levels in soils, but consistently at concentrations much lower than were applied, and even pulsed concentrations declined rapidly. Different natural soils varied substantially in the retention of (+/-)-catechin after application but consistent rapid decreases in concentrations over time suggested that applied experimental concentrations may overestimate concentrations necessary for phytotoxicity by over an order of magnitude. (+/-)-Catechin was not phytotoxic to Bambusa arundinacea in natural Indian soil in a single pulse, but soil concentrations at the time of planting seeds were either undetectable or very low. However, a single dose of (+/-)-catechin suppressed the growth of bamboo in sand, in soil mixed with organic matter, and Koeleria macrantha in soils from Montana and Romania, and in field applications at 40 microg l(-1). Multiple pulses of (+/-)-catechin were inhibitory at very low concentrations in Indian soil. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that (+/-)-catechin is highly dynamic in natural soils, but is phytotoxic well below natural concentrations measured in some soils and applied at low concentrations in the field. However, there is substantial conditionality in the effects of the allelochemical

Study of CP violation in Dalitz-plot analyses of B0 --> K+K-KS, B+ --> K+K-K+, and B+ --> KSKSK+

We perform amplitude analyses of the decays $B^0 \to K^+K^-K^0_S$, $B^+ \rightarrow K^+K^-K^+$, and $B^+ \to K^0_S K^0_S K^+$, and measure CP-violating parameters and partial branching fractions. The results are based on a data sample of approximately $470\times 10^6$ $B\bar{B}$ decays, collected with the BABAR detector at the PEP-II asymmetric-energy $B$ factory at the SLAC National Accelerator Laboratory. For $B^+ \to K^+K^-K^+$, we find a direct CP asymmetry in $B^+ \to \phi(1020)K^+$ of $A_{CP}= (12.8\pm 4.4 \pm 1.3)$, which differs from zero by $2.8 \sigma$. For $B^0 \to K^+K^-K^0_S$, we measure the CP-violating phase $\beta_{\rm eff} (\phi(1020)K^0_S) = (21\pm 6 \pm 2)^\circ$. For $B^+ \to K^0_S K^0_S K^+$, we measure an overall direct CP asymmetry of $A_{CP} = (4 ^{+4}_{-5} \pm 2)$. We also perform an angular-moment analysis of the three channels, and determine that the $f_X(1500)$ state can be described well by the sum of the resonances $f_0(1500)$, $f_2^{\prime}(1525)$, and $f_0(1710)$.Comment: 35 pages, 68 postscript figures. v3 - minor modifications to agree with published versio

Observation and study of baryonic B decays: B -> D(*) p pbar, D(*) p pbar pi, and D(*) p pbar pi pi

We present a study of ten B-meson decays to a D(*), a proton-antiproton pair, and a system of up to two pions using BaBar's data set of 455x10^6 BBbar pairs. Four of the modes (B0bar -> D0 p anti-p, B0bar -> D*0 p anti-p, B0bar -> D+ p anti-p pi-, B0bar -> D*+ p anti-p pi-) are studied with improved statistics compared to previous measurements; six of the modes (B- -> D0 p anti-p pi-, B- -> D*0 p anti-p pi-, B0bar -> D0 p anti-p pi- pi+, B0bar -> D*0 p anti-p pi- pi+, B- -> D+ p anti-p pi- pi-, B- -> D*+ p anti-p pi- pi-) are first observations. The branching fractions for 3- and 5-body decays are suppressed compared to 4-body decays. Kinematic distributions for 3-body decays show non-overlapping threshold enhancements in m(p anti-p) and m(D(*)0 p) in the Dalitz plots. For 4-body decays, m(p pi-) mass projections show a narrow peak with mass and full width of (1497.4 +- 3.0 +- 0.9) MeV/c2, and (47 +- 12 +- 4) MeV/c2, respectively, where the first (second) errors are statistical (systematic). For 5-body decays, mass projections are similar to phase space expectations. All results are preliminary.Comment: 28 pages, 90 postscript figures, submitted to LP0

Digit Ratio Predicts Sense of Direction in Women

The relative length of the second-to-fourth digits (2D:4D) has been linked with prenatal androgen in humans. The 2D:4D is sexually dimorphic, with lower values in males than females, and appears to correlate with diverse measures of behavior. However, the relationship between digit ratio and cognition, and spatial cognition in particular, has produced mixed results. In the present study, we hypothesized that spatial tasks separating cue conditions that either favored female or male strategies would examine this structure-function correlation with greater precision. Previous work suggests that males are better in the use of directional cues than females. In the present study, participants learned a target location in a virtual landscape environment, in conditions that contained either all directional (i.e., distant or compass bearing) cues, or all positional (i.e., local, small objects) cues. After a short delay, participants navigated back to the target location from a novel starting location. Males had higher accuracy in initial search direction than females in environments with all directional cues. Lower digit ratio was correlated with higher accuracy of initial search direction in females in environments with all directional cues. Mental rotation scores did not correlate with digit ratio in either males or females. These results demonstrate for the first time that a sex difference in the use of directional cues, i.e., the sense of direction, is associated with more male-like digit ratio.National Science Foundation (U.S.) (NSF ECCS-1028319)National Science Foundation (U.S.) (NSF Graduate Student Fellowship)Mary Elisabeth Rennie Endowment for Epilepsy Researc

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Predicting complete loss to follow-up after a health-education program: number of absences and face-to-face contact with a researcher

<p>Abstract</p> <p>Background</p> <p>Research on health-education programs requires longitudinal data. Loss to follow-up can lead to imprecision and bias, and <it>complete </it>loss to follow-up is particularly damaging. If that loss is predictable, then efforts to prevent it can be focused on those program participants who are at the highest risk. We identified predictors of complete loss to follow-up in a longitudinal cohort study.</p> <p>Methods</p> <p>Data were collected over 1 year in a study of adults with chronic illnesses who were in a program to learn self-management skills. Following baseline measurements, the program had one group-discussion session each week for six weeks. Follow-up questionnaires were sent 3, 6, and 12 months after the baseline measurement. A person was classified as completely lost to follow-up if none of those three follow-up questionnaires had been returned by two months after the last one was sent.</p> <p>We tested two hypotheses: that complete loss to follow-up was directly associated with the number of absences from the program sessions, and that it was less common among people who had had face-to-face contact with one of the researchers. We also tested predictors of data loss identified previously and examined associations with specific diagnoses.</p> <p>Using the unpaired t-test, the U test, Fisher's exact test, and logistic regression, we identified good predictors of complete loss to follow-up.</p> <p>Results</p> <p>The prevalence of complete loss to follow-up was 12.2% (50/409). Complete loss to follow-up was directly related to the number of absences (odds ratio; 95% confidence interval: 1.78; 1.49-2.12), and it was inversely related to age (0.97; 0.95-0.99). Complete loss to follow-up was less common among people who had met one of the researchers (0.51; 0.28-0.95) and among those with connective tissue disease (0.29; 0.09-0.98). For the multivariate logistic model the area under the ROC curve was 0.77.</p> <p>Conclusions</p> <p>Complete loss to follow-up after this health-education program can be predicted to some extent from data that are easy to collect (age, number of absences, and diagnosis). Also, face-to-face contact with a researcher deserves further study as a way of increasing participation in follow-up, and health-education programs should include it.</p

MOSAIC (MOthers' Advocates In the Community): protocol and sample description of a cluster randomised trial of mentor mother support to reduce intimate partner violence among pregnant or recent mothers

Background : Intimate partner violence (IPV) is prevalent globally, experienced by a significant minority of women in the early childbearing years and is harmful to the mental and physical health of women and children. There are very few studies with rigorous designs which have tested the effectiveness of IPV interventions to improve the health and wellbeing of abused women. Evidence for the separate benefit to victims of social support, advocacy and non-professional mentoring suggested that a combined model may reduce the levels of violence, the associated mental health damage and may increase a woman\u27s health, safety and connection with her children. This paper describes the development, design and implementation of a trial of mentor mother support set in primary care, including baseline characteristics of participating women.Methods/Design : MOSAIC (MOtherS\u27 Advocates In the Community) was a cluster randomised trial embedded in general practice and maternal and child health (MCH) nursing services in disadvantaged suburbs of Melbourne, Australia. Women who were pregnant or with infants, identified as abused or symptomatic of abuse, were referred by IPV-trained GPs and MCH nurses from 24 general practices and eight nurse teams from January 2006 to December 2007. Women in the intervention arm received up to 12 months support from trained and supported non-professional mentor mothers. Vietnamese health professionals also referred Vietnamese women to bilingual mentors in a sub-study. Baseline and follow-up surveys at 12 months measured IPV (CAS), depression (EPDS), general health (SF-36), social support (MOS-SF) and attachment to children (PSI-SF). Significant development and piloting occurred prior to trial commencement. Implementation interviews with MCH nurses, GPs and mentors assisted further refinement of the intervention. In-depth interviews with participants and mentors, and follow-up surveys of MCH nurses and GPs at trial conclusion will shed further light on MOSAIC\u27s impact.Discussion : Despite significant challenges, MOSAIC will make an important contribution to the need for evidence of effective partner violence interventions, the role of non-professional mentors in partner violence support services and the need for more evaluation of effective health professional training and support in caring for abused women and children among their populations.<br /

A Validated Model of Serum Anti-Müllerian Hormone from Conception to Menopause

Background Anti-Müllerian hormone (AMH) is a product of growing ovarian follicles. The concentration of AMH in blood may also reflect the non-growing follicle (NGF) population, i.e. the ovarian reserve, and be of value in predicting reproductive lifespan. A full description of AMH production up to the menopause has not been previously reported. Methodology/Principal Findings By searching the published literature for AMH concentrations in healthy pre-menopausal females, and using our own data (combined ) we have generated and robustly validated the first model of AMH concentration from conception to menopause. This model shows that 34% of the variation in AMH is due to age alone. We have shown that AMH peaks at age 24.5 years, followed by a decline to the menopause. We have also shown that there is a neonatal peak and a potential pre-pubertal peak. Our model allows us to generate normative data at all ages. Conclusions/Significance These data highlight key inflection points in ovarian follicle dynamics. This first validated model of circulating AMH in healthy females describes a transition period in early adulthood, after which AMH reflects the progressive loss of the NGF pool. The existence of a neonatal increase in gonadal activity is confirmed for females. An improved understanding of the relationship between circulating AMH and age will lead to more accurate assessment of ovarian reserve for the individual woman.Publisher PDFPeer reviewe

The Related Transcriptional Enhancer Factor-1 Isoform, TEAD4216, Can Repress Vascular Endothelial Growth Factor Expression in Mammalian Cells

Increased cellular production of vascular endothelial growth factor (VEGF) is responsible for the development and progression of multiple cancers and other neovascular conditions, and therapies targeting post-translational VEGF products are used in the treatment of these diseases. Development of methods to control and modify the transcription of the VEGF gene is an alternative approach that may have therapeutic potential. We have previously shown that isoforms of the transcriptional enhancer factor 1-related (TEAD4) protein can enhance the production of VEGF. In this study we describe a new TEAD4 isoform, TEAD4216, which represses VEGF promoter activity. The TEAD4216 isoform inhibits human VEGF promoter activity and does not require the presence of the hypoxia responsive element (HRE), which is the sequence critical to hypoxia inducible factor (HIF)-mediated effects. The TEAD4216 protein is localized to the cytoplasm, whereas the enhancer isoforms are found within the nucleus. The TEAD4216 isoform can competitively repress the stimulatory activity of the TEAD4434 and TEAD4148 enhancers. Synthesis of the native VEGF165 protein and cellular proliferation is suppressed by the TEAD4216 isoform. Mutational analysis indicates that nuclear or cytoplasmic localization of any isoform determines whether it acts as an enhancer or repressor, respectively. The TEAD4216 isoform appears to inhibit VEGF production independently of the HRE required activity by HIF, suggesting that this alternatively spliced isoform of TEAD4 may provide a novel approach to treat VEGF-dependent diseases