Associations between diagnostic time intervals and health-related quality of life, clinical anxiety and depression in adolescents and young adults with cancer:cross-sectional analysis of the BRIGHTLIGHT cohort

The association of diagnostic intervals and outcomes is poorly understood in adolescents and young adults with cancer (AYA). We investigated associations between diagnostic intervals and health-related quality of life (HRQoL), anxiety and depression in a large AYA cohort.Participants aged 12-24 completed interviews post-diagnosis, providing data on diagnostic experiences and the patient-reported outcomes (PROs) HRQoL, anxiety and depression. Demographic and cancer information were obtained from clinical and national records. Six diagnostic intervals were considered. Relationships between intervals and PROs were examined using regression models.Eight hundred and thirty participants completed interviews. In adjusted models, across 28 of 30 associations, longer intervals were associated with poorer PROs. Patient intervals (symptom onset to first seeing a GP) of ≥1 month were associated with greater depression (adjusted odds ratio (aOR):1.7, 95% Confidence Interval (CI):1.1-2.5) compared to <1 month. ≥3 pre-referral GP consultations were associated with greater anxiety (aOR:1.6, CI:1.1-2.3) compared to 1-2 consultations. Symptom onset to first oncology appointment intervals of ≥2 months was associated with impaired HRQoL (aOR:1.8, CI:1.2-2.5) compared to <2 months.Prolonged diagnostic intervals in AYA are associated with an increased risk of impaired HRQoL, anxiety and depression. Identifying and delivering interventions for this high-risk group is a priority

Absence of the Filarial Endosymbiont Wolbachia in Seal Heartworm (Acanthocheilonema spirocauda) but Evidence of Ancient Lateral Gene Transfer

The symbiotic relationship of Wolbachia spp. was first observed in insects and subsequently in many parasitic filarial nematodes. This bacterium is believed to provide metabolic and developmental assistance to filarial parasitic nematodes, although the exact nature of this relationship remains to be fully elucidated. While Wolbachia is present in most filarial nematodes in the familyOnchocercidae, it is absent in several disparate species such as the human parasite Loa loa. All tested members of the genusAcanthocheilonema, such as Acanthocheilonema viteae, have been shown to lack Wolbachia. Consistent with this, we show thatWolbachia is absent from the seal heartworm (Acanthocheilonema spirocauda), but lateral gene transfer (LGT) of DNA sequences between Wolbachia and A. spirocauda has occurred, indicating a past evolutionary association. Seal heartworm is an important pathogen of phocid seals and understanding its basic biology is essential for conservation of the host. The findings presented here may allow for the development of future treatments or diagnostics for the disease and also aid in clarification of the complicated nematode–Wolbachia relationship

t1/3t^{1/3} Superdiffusivity of Finite-Range Asymmetric Exclusion Processes on Z\mathbb Z

We consider finite-range asymmetric exclusion processes on $\mathbb Z$ with non-zero drift. The diffusivity $D(t)$ is expected to be of ${\mathcal O}(t^{1/3})$. We prove that $D(t)\ge Ct^{1/3}$ in the weak (Tauberian) sense that $\int_0^\infty e^{-\lambda t}tD(t)dt \ge C\lambda^{-7/3}$ as $\lambda\to 0$. The proof employs the resolvent method to make a direct comparison with the totally asymmetric simple exclusion process, for which the result is a consequence of the scaling limit for the two-point function recently obtained by Ferrari and Spohn. In the nearest neighbor case, we show further that $tD(t)$ is monotone, and hence we can conclude that $D(t)\ge Ct^{1/3}(\log t)^{-7/3}$ in the usual sense.Comment: Version 3. Statement of Theorem 3 is correcte

Clustering Properties of restframe UV selected galaxies I: the correlation length derived from GALEX data in the local Universe

We present the first measurements of the angular correlation function of galaxies selected in the far (1530 A) and near (2310 A) Ultraviolet from the GALEX survey fields overlapping SDSS DR5 in low galactic extinction regions. The area used covers 120 sqdeg (GALEX - MIS) down to magnitude AB = 22, yielding a total of 100,000 galaxies. The mean correlation length is ~ 3.7 \pm 0.6 Mpc and no significant trend is seen for this value as a function of the limiting apparent magnitude or between the GALEX bands. This estimate is close to that found from samples of blue galaxies in the local universe selected in the visible, and similar to that derived at z ~ 3 for LBGs with similar rest frame selection criteria. This result supports models that predict anti-biasing of star forming galaxies at low redshift, and brings an additional clue to the downsizing of star formation at z<1.Comment: Accepted for publication in GALEX Special ApJs, December 200

Clustering Properties of restframe UV selected galaxies II: Migration of Star Formation sites with cosmic time from GALEX and CFHTLS

We analyze the clustering properties of ultraviolet selected galaxies by using GALEX-SDSS data at z<0.6 and CFHTLS deep u' imaging at z=1. These datasets provide a unique basis at z< 1 which can be directly compared with high redshift samples built with similar selection criteria. We discuss the dependence of the correlation function parameters (r0, delta) on the ultraviolet luminosity as well as the linear bias evolution. We find that the bias parameter shows a gradual decline from high (b > 2) to low redshift (b ~ 0.79^{+0.1}_{-0.08}). When accounting for the fraction of the star formation activity enclosed in the different samples, our results suggest that the bulk of star formation migrated from high mass dark matter halos at z>2 (10^12 < M_min < 10^13 M_sun, located in high density regions), to less massive halos at low redshift (M_min < 10^12 M_sun, located in low density regions). This result extends the ``downsizing'' picture (shift of the star formation activity from high stellar mass systems at high z to low stellar mass at low z) to the dark matter distribution.Comment: Accepted for Publication in the Special GALEX Ap. J. Supplement, December 2007 Version with full resolution fig1 available at http://taltos.pha.jhu.edu/~sebastien/papers/Galex_p2.ps.g

Number Counts of GALEX Sources in FUV (1530A) and NUV (2310A) Bands

Number Counts of galaxies in two GALEX bands (FUV: 1530A and NUV: 2310A, both in AB magnitudes) are reported. They provide for the first time in the literature homogeneously calibrated number counts of UV galaxies covering continuously a very wide range of UV magnitude (14 -- 23.8). Both the FUV and NUV counts are inconsistent with a non-evolution model, while they are in good agreement with evolution models (essentially luminosity evolution) derived from the high-z UV luminosity functions of Arnouts et al. (2004). It is found that the contribution from galaxies detected by GALEX to the UV background is 0.68+-0.10 nW m-2 sr-1 at 1530A and 0.99+-0.15 nW m-2 sr-1 at 2310A. These are 66+-9% and 44+-6% of the total contributions of galaxies to the the UV background at 1530A, respectively, as estimated using the evolution models. ...Comment: This paper will be published as part of the Galaxy Evolution Explorer (GALEX) Astrophysical Journal Letters Special Issue. Links to the full set of papers will be available at http:/www.galex.caltech.edu/PUBLICATIONS/ after November 22, 200

New Mouse Lines for the Analysis of Neuronal Morphology Using CreER(T)/loxP-Directed Sparse Labeling

BACKGROUND: Pharmacologic control of Cre-mediated recombination using tamoxifen-dependent activation of a Cre-estrogen receptor ligand binding domain fusion protein [CreER(T)] is widely used to modify and/or visualize cells in the mouse. METHODS AND FINDINGS: We describe here two new mouse lines, constructed by gene targeting to the Rosa26 locus to facilitate Cre-mediated cell modification. These lines should prove particularly useful in the context of sparse labeling experiments. The R26rtTACreER line provides ubiquitous expression of CreER under transcriptional control by the tetracycline reverse transactivator (rtTA); dual control by doxycycline and tamoxifen provides an extended dynamic range of Cre-mediated recombination activity. The R26IAP line provides high efficiency Cre-mediated activation of human placental alkaline phosphatase (hPLAP), complementing the widely used, but low efficiency, Z/AP line. By crossing with mouse lines that direct cell-type specific CreER expression, the R26IAP line has been used to produce atlases of labeled cholinergic and catecholaminergic neurons in the mouse brain. The R26IAP line has also been used to visualize the full morphologies of retinal dopaminergic amacrine cells, among the largest neurons in the mammalian retina. CONCLUSIONS: The two new mouse lines described here expand the repertoire of genetically engineered mice available for controlled in vivo recombination and cell labeling using the Cre-lox system

COSMOS: COmparing Standard Maternity care with One-to-one midwifery Support: a randomised controlled trial

Background: In Australia and internationally, there is concern about the growing proportion of women giving birth by caesarean section. There is evidence of increased risk of placenta accreta and percreta in subsequent pregnancies as well as decreased fertility; and significant resource implications. Randomised controlled trials (RCTs) of continuity of midwifery care have reported reduced caesareans and other interventions in labour, as well as increased maternal satisfaction, with no statistically significant differences in perinatal morbidity or mortality. RCTs conducted in the UK and in Australia have largely measured the effect of teams of care providers (commonly 6&ndash;12 midwives) with very few testing caseload (one-to-one) midwifery care. This study aims to determine whether caseload (one-to-one) midwifery care for women at low risk of medical complications decreases the proportion of women delivering by caesarean section compared with women receiving \u27standard\u27 care. This paper presents the trial protocol in detail.Methods/design: A two-arm RCT design will be used. Women who are identified at low medical risk will be recruited from the antenatal booking clinics of a tertiary women\u27s hospital in Melbourne, Australia. Baseline data will be collected, then women randomised to caseload midwifery or standard low risk care. Women allocated to the caseload intervention will receive antenatal, intrapartum and postpartum care from a designated primary midwife with one or two antenatal visits conducted by a \u27back-up\u27 midwife. The midwives will collaborate with obstetricians and other health professionals as necessary. If the woman has an extended labour, or if the primary midwife is unavailable, care will be provided by the back-up midwife. For women allocated to standard care, options include midwifery-led care with varying levels of continuity, junior obstetric care and community based general medical practitioner care. Data will be collected at recruitment (self administered survey) and at 2 and 6 months postpartum by postal survey. Medical/obstetric outcomes will be abstracted from the medical record. The sample size of 2008 was calculated to identify a decrease in caesarean birth from 19 to 14% and detect a range of other significant clinical differences. Comprehensive process and economic evaluations will be conducted.Trial registration: Australian New Zealand Clinical Trials Registry ACTRN012607000073404.<br /

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer