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To evaluate the impact of a liquid chromatography-tandem mass spectrometry (LCMSMS) second-tier test on newborn screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) in New Zealand.

In a prospective study, a LCMSMS method to measure 17-hydroxyprogesterone (17OHP) was adapted to measure four additional steroids. Steroid concentrations were collected on all second-tier CAH screening tests while protocols remained unchanged. Steroid ratio parameters with recommended or published screening cuts-offs were evaluated for their impact on newborn screening performance.

Precision, accuracy, linearity and recovery of the second-tier LCMSMS method were evaluated. Second-tier specimens were divided in 3 groups; newborn screening bloodspots from neonates with confirmed CAH (n=7) and 2 groups specimens from neonates with a birthweight (BW) ≤1500g (n=795) and with a BW>1500g (n=806) with a negative newborn screening test. Six protocols using four steroid ratio parameters were evaluated. The sensitivity, specificity, false positive rate and positive predictive value of screening was calculated for each protocol.

The LCMSMS method was sufficiently accurate and precise to be used as a second-tier test for CAH. Screening sensitivity remained at 100% for each protocol apart from (17OHP+androstenedione)/cortisol when the highest cut-off of 3.75 was applied. The false positive rate was significantly improved when (17OHP+androstenedione)/cortisol and (17OHP+21-deoxycortisol)/cortisol were evaluated with cut-offs of 2.5 and 1.5 respectively (P<.01) and both with a positive predictive value of 64%.

A second-tier LCMSMS newborn screening test for CAH offers significant improvements to screening specificity without any other changes to screening protocols.

A second-tier LCMSMS newborn screening test for CAH offers significant improvements to screening specificity without any other changes to screening protocols.

We have previously observed that in response to antigenic activation, T cells produce actin-rich protrusions that generate forces involved in T cell activation. These forces are influenced by the mechanical properties of antigen-presenting cells (APCs). However, how external forces, which can be produced by APCs, influence the dynamic of the actin protrusion remains unknown. In this study, we quantitatively characterised the effects of external forces in the dynamic of the protrusion grown by activated T cells.

Using a micropipette force probe, we applied controlled compressive or pulling forces on primary T lymphocytes activated by an antibody-covered microbead, and measured the effects of these forces on the protrusion generated by T lymphocytes. We found that the application of compressive forces slightly decreased the length, the time at which the protrusion stops growing and retracts and the velocity of the protrusion formation, whereas pulling forces strongly increased these parameters. In both casemodify their dynamic suggesting that they might modify immune responses. Moreover, the quantitative aspects of our analysis should help to get insight into the molecular mechanisms involved in the formation of the protrusion.

Actin-rich protrusions developed by T cells are sensory organelles that serve as actuators of immune surveillance. Our study shows that forces experienced by this organelle modify their dynamic suggesting that they might modify immune responses. Moreover, the quantitative aspects of our analysis should help to get insight into the molecular mechanisms involved in the formation of the protrusion.Animals often need to invest significantly in mating behaviour in order to successfully mate. However, the expression of mating behaviour can be costly, especially in unfavourable environments, so animals are expected to adjust their behaviour in a context-dependent way to mitigate these costs. I systematically searched the literature for studies measuring animal mating behaviour (sexual signalling, response to sexual signals or the strength of mate choice) in more than one environment, and used a phylogenetically controlled meta-analysis to identify environmental factors influencing these behaviours. Across 222 studies, the strength of mate choice was significantly context-dependent, and most strongly influenced by population density, population sex ratio and predation risk. However, the average effect sizes were typically small. The amount of sexual signalling and the strength of response to sexual signals were not significantly related to the environment. Overall, this suggests that the evidence for context-dependent mating behaviour across animals is surprisingly weak.

To compare the oncologic outcomes of radical prostatectomy (RP) versus external beam radiotherapy (EBRT) ± androgen deprivation therapy for primary treatment of high risk localized prostate cancer (CaP).

We retrospectively reviewed a prospectively-populated database for cases who underwent primary treatment for high risk localized CaP, had more than 2 years follow-up, and were treated since 2006. A total of 335 cases were studied of whom 291 underwent RP and 44 underwent EBRT. Clinical characteristics, biochemical progression-free survival (BPFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) were compared.

EBRT cases were older (p < .01; mean 71 years vs. 61 years) and had longer PSA doubling time (PSADT) (p = .03; median 4.8 years vs. 3.5 years) than RP. Race, pretreatment PSA and biopsy Gleason score were similar. Median follow-up was 5.1 (range 2.3-12.8) years for RP versus 3.3 (range 2-12.4) years for EBRT. Three- and 5-year BPFS were 42% and 36% after RP versus 86% and 75% after EBRT (p < .01). The rate of adjuvant/salvage therapy was 58% after RP versus 20% after EBRT (p < .01). Three- and 5-year MFS were 80% and 77% after RP versus 91% and 91% after EBRT (p = .11). Three-year CSS was 98% in both groups and OS was 97% after RP versus 94% after EBRT (p = .73).

RP had higher rates of biochemical failure and adjuvant or salvage treatment versus EBRT in high risk localized CaP. learn more MFS trended toward benefit after EBRT, but CSS and OS remained high in both groups.

RP had higher rates of biochemical failure and adjuvant or salvage treatment versus EBRT in high risk localized CaP. MFS trended toward benefit after EBRT, but CSS and OS remained high in both groups.

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