Radiometric approach for the detection of picophytoplankton assemblages across oceanic fronts

Cell abundances of Prochlorococcus, Synechococcus, and autotrophic picoeukaryotes were estimated in surface waters using principal component analysis (PCA) of hyperspectral and multispectral remote-sensing reflectance data. This involved the development of models that employed multilinear correlations between cell abundances across the Atlantic Ocean and a combination of PCA scores and sea surface temperatures. The models retrieve high Prochlorococcus abundances in the Equatorial Convergence Zone and show their numerical dominance in oceanic gyres, with decreases in Prochlorococcus abundances towards temperate waters where Synechococcus flourishes, and an emergence of picoeukaryotes in temperate waters. Fine-scale in-situ sampling across ocean fronts provided a large dynamic range of measurements for the training dataset, which resulted in the successful detection of fine-scale Synechococcus patches. Satellite implementation of the models showed good performance (R2> 0.50) when validated against in-situ data from six Atlantic Meridional Transect cruises. The improved relative performance of the hyperspectral models highlights the importance of future high spectral resolution satellite instruments, such as the NASA PACE mission’s Ocean Color Instrument, to extend our spatiotemporal knowledge about ecologically relevant phytoplankton assemblage

Random walk on the range of random walk

We study the random walk X on the range of a simple random walk on ℤ d in dimensions d≥4. When d≥5 we establish quenched and annealed scaling limits for the process X, which show that the intersections of the original simple random walk path are essentially unimportant. For d=4 our results are less precise, but we are able to show that any scaling limit for X will require logarithmic corrections to the polynomial scaling factors seen in higher dimensions. Furthermore, we demonstrate that when d=4 similar logarithmic corrections are necessary in describing the asymptotic behavior of the return probability of X to the origin

Comparison of the cellular cytotoxic activities of colostral lymphocytes and maternal peripheral blood lymphocytes

Colostral lymphocytes (CL) from mothers 2 to 4 days post-partum and autologous maternal peripheral blood lymphocytes (PBL) were investigated for (1) natural killer (NK) and antibody-dependent cellular cytotoxic (ADCC) activities, (2) target binding ability, (3) interferon (IFN)- and interleukin 2 (IL2)-induced augmentation of NK activity, (4) lectin-dependent cellular cytotoxicity (LDCC), and (5) the ability of culture-derived soluble suppressor factor(s) to inhibit the NK activity of normal allogeneic lymphocytes. CL depleted of adherent cells and Percoll-separated NK-enriched subpopulations of CL demonstrated significantly lower NK and ADCC activities compared to autologous PBL. However, the target binding ability of CL was comparable to autologous PBL. Although the residual NK activity of CL was augmented by IFN and IL2, the activity was not enhanced to the same level shown by autologous PBL. CL also demonstrated a significant enhancement of LDCC activity, although the activity was not stimulated to the levels shown by PBL. Culture supernates of CL manifested greater suppression of the NK ability of allogeneic PBL than culture supernates produced by autologous PBL. These results are consistent with a model that suggests differential partitioning of lymphocyte subpopulations between colostrum and peripheral blood.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25675/1/0000228.pd

Radiometric approach for the detection of picophytoplankton assemblages across oceanic fronts

Cell abundances of Prochlorococcus, Synechococcus, and autotrophic picoeukaryotes were estimated in surface waters using principal component analysis (PCA) of hyperspectral and multispectral remote-sensing reflectance data. This involved the development of models that employed multilinear correlations between cell abundances across the Atlantic Ocean and a combination of PCA scores and sea surface temperatures. The models retrieve high Prochlorococcus abundances in the Equatorial Convergence Zone and show their numerical dominance in oceanic gyres, with decreases in Prochlorococcus abundances towards temperate waters where Synechococcus flourishes, and an emergence of picoeukaryotes in temperate waters. Fine-scale in-situ sampling across ocean fronts provided a large dynamic range of measurements for the training dataset, which resulted in the successful detection of fine-scale Synechococcus patches. Satellite implementation of the models showed good performance (R2 > 0.50) when validated against in-situ data from six Atlantic Meridional Transect cruises. The improved relative performance of the hyperspectral models highlights the importance of future high spectral resolution satellite instruments, such as the NASA PACE mission’s Ocean Color Instrument, to extend our spatiotemporal knowledge about ecologically relevant phytoplankton assemblages

Onset of common mental disorders and suicidal behavior following women's first exposure to gender based violence: a retrospective, population-based study

Published: 18 November 2014BACKGROUND: Women exposed to gender-based violence (GBV) experience a high rate of common mental disorders and suicidal behaviour ("mental disturbance"). Little is known however about the timing of onset of mental disturbance following first exposure to GBV amongst women with no prior mental disorder. METHODS: The analysis was undertaken on the Australian National Mental Health and Wellbeing Survey dataset (N = 8841). We assessed lifetime prevalence and first onset of common mental disorder and suicidal behaviour (mental disturbance) and exposure to GBV and its first occurrence based on the Composite International Diagnostic Interview Version 3 (WMH-CIDI 3.0). We used the Kaplan-Meier method to derive cumulative incident curves for first onset mental disturbance. The two derived subgroups were women who experienced GBV without prior mental disturbance; and women never exposed to GBV stratified to match the former group on age and socio-economic status. RESULTS: For women with no prior mental disorder, the cumulative incidence curves showed a high incidence of all mental disturbances following first GBV, compared to women without exposure to GBV (all log rank tests <0.0001). Nearly two fifths (37%) of any lifetime mental disturbance had onset in the year following first GBV in women exposed to abuse. For these women, over half (57%) of cases of lifetime PTSD had onset in the same time interval. For GBV exposed women, half of all cases of mental disturbance (54%) and two thirds of cases of PTSD (66.9%) had onset in the five years following first abuse. In contrast, there was a low prevalence of onset of mental disturbance in the comparable imputed time to event period for women never exposed to GBV (for any mental disturbance, 1% in the first year, 12% in five years; for PTSD 3% in the first year, 7% in five years). CONCLUSIONS: Amongst women without prior mental disturbance, common mental disorders and suicidal behaviour have a high rate of onset in the one and five year intervals following exposure to GBV. There is a particularly high incidence of PTSD in the first year following GBV.Susan Rees, Zachary Steel, Mark Creamer, Maree Teesson, Richard Bryant, Alexander C McFarlane, Katherine L Mills, Tim Slade, Natacha Carragher, Meaghan O, Donnell, David Forbes and Derrick Silov

Critical Exponents, Hyperscaling and Universal Amplitude Ratios for Two- and Three-Dimensional Self-Avoiding Walks

We make a high-precision Monte Carlo study of two- and three-dimensional self-avoiding walks (SAWs) of length up to 80000 steps, using the pivot algorithm and the Karp-Luby algorithm. We study the critical exponents $\nu$ and $2\Delta_4 -\gamma$ as well as several universal amplitude ratios; in particular, we make an extremely sensitive test of the hyperscaling relation $d\nu = 2\Delta_4 -\gamma$. In two dimensions, we confirm the predicted exponent $\nu = 3/4$ and the hyperscaling relation; we estimate the universal ratios $\ / \ = 0.14026 \pm 0.00007$, $\ / \ = 0.43961 \pm 0.00034$ and $\Psi^* = 0.66296 \pm 0.00043$ (68\% confidence limits). In three dimensions, we estimate $\nu = 0.5877 \pm 0.0006$ with a correction-to-scaling exponent $\Delta_1 = 0.56 \pm 0.03$ (subjective 68\% confidence limits). This value for $\nu$ agrees excellently with the field-theoretic renormalization-group prediction, but there is some discrepancy for $\Delta_1$. Earlier Monte Carlo estimates of $\nu$, which were $\approx\! 0.592$, are now seen to be biased by corrections to scaling. We estimate the universal ratios $\ / \ = 0.1599 \pm 0.0002$ and $\Psi^* = 0.2471 \pm 0.0003$; since $\Psi^* > 0$, hyperscaling holds. The approach to $\Psi^*$ is from above, contrary to the prediction of the two-parameter renormalization-group theory. We critically reexamine this theory, and explain where the error lies.Comment: 87 pages including 12 figures, 1029558 bytes Postscript (NYU-TH-94/09/01

A phase I dose-escalation study of enzalutamide in combination with the AKT inhibitor AZD5363 (capivasertib) in patients with metastatic castration-resistant prostate cancer.

Background Activation of the PI3K/AKT/mTOR pathway through loss of phosphatase and tensin homolog (PTEN) occurs in approximately 50% of patients with metastatic castration-resistant prostate cancer (mCRPC). Recent evidence suggests that combined inhibition of the androgen receptor (AR) and AKT may be beneficial in mCRPC with PTEN loss.Patients and methods mCRPC patients who previously failed abiraterone and/or enzalutamide, received escalating doses of AZD5363 (capivasertib) starting at 320 mg twice daily (b.i.d.) given 4 days on and 3 days off, in combination with enzalutamide 160 mg daily. The co-primary endpoints were safety/tolerability and determining the maximum tolerated dose and recommended phase II dose; pharmacokinetics, antitumour activity, and exploratory biomarker analysis were also evaluated.Results Sixteen patients were enrolled, 15 received study treatment and 13 were assessable for dose-limiting toxicities (DLTs). Patients were treated at 320, 400, and 480 mg b.i.d. dose levels of capivasertib. The recommended phase II dose identified for capivasertib was 400 mg b.i.d. with 1/6 patients experiencing a DLT (maculopapular rash) at this level. The most common grade ≥3 adverse events were hyperglycemia (26.7%) and rash (20%). Concomitant administration of enzalutamide significantly decreased plasma exposure of capivasertib, though this did not appear to impact pharmacodynamics. Three patients met the criteria for response (defined as prostate-specific antigen decline ≥50%, circulating tumour cell conversion, and/or radiological response). Responses were seen in patients with PTEN loss or activating mutations in AKT, low or absent AR-V7 expression, as well as those with an increase in phosphorylated extracellular signal-regulated kinase (pERK) in post-exposure samples.Conclusions The combination of capivasertib and enzalutamide is tolerable and has antitumour activity, with all responding patients harbouring aberrations in the PI3K/AKT/mTOR pathway.Clinical trial number NCT02525068

Communication style and exercise compliance in physiotherapy (CONNECT). A cluster randomized controlled trial to test a theory-based intervention to increase chronic low back pain patients’ adherence to physiotherapists’ recommendations: study rationale, design, and methods

Physical activity and exercise therapy are among the accepted clinical rehabilitation guidelines and are recommended self-management strategies for chronic low back pain. However, many back pain sufferers do not adhere to their physiotherapist’s recommendations. Poor patient adherence may decrease the effectiveness of advice and home-based rehabilitation exercises. According to self-determination theory, support from health care practitioners can promote patients’ autonomous motivation and greater long-term behavioral persistence (e.g., adherence to physiotherapists’ recommendations). The aim of this trial is to assess the effect of an intervention designed to increase physiotherapists’ autonomy-supportive communication on low back pain patients’ adherence to physical activity and exercise therapy recommendations. \ud \ud This study will be a single-blinded cluster randomized controlled trial. Outpatient physiotherapy centers (N =12) in Dublin, Ireland (population = 1.25 million) will be randomly assigned using a computer-generated algorithm to either the experimental or control arm. Physiotherapists in the experimental arm (two hospitals and four primary care clinics) will attend eight hours of communication skills training. Training will include handouts, workbooks, video examples, role-play, and discussion designed to teach physiotherapists how to communicate in a manner that promotes autonomous patient motivation. Physiotherapists in the waitlist control arm (two hospitals and four primary care clinics) will not receive this training. Participants (N = 292) with chronic low back pain will complete assessments at baseline, as well as 1 week, 4 weeks, 12 weeks, and 24 weeks after their first physiotherapy appointment. Primary outcomes will include adherence to physiotherapy recommendations, as well as low back pain, function, and well-being. Participants will be blinded to treatment allocation, as they will not be told if their physiotherapist has received the communication skills training. Outcome assessors will also be blinded. \ud \ud We will use linear mixed modeling to test between arm differences both in the mean levels and the rates of change of the outcome variables. We will employ structural equation modeling to examine the process of change, including hypothesized mediation effects. \ud \ud This trial will be the first to test the effect of a self-determination theory-based communication skills training program for physiotherapists on their low back pain patients’ adherence to rehabilitation recommendations. Current Controlled Trials ISRCTN63723433\u

Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian cancer patients.

Advances in DNA sequencing have made genetic testing fast and affordable, but limitations of testing processes are impeding realisation of patient benefits. Ovarian cancer exemplifies the potential value of genetic testing and the shortcomings of current pathways to access testing. Approximately 15% of ovarian cancer patients have a germline BRCA1 or BRCA2 mutation which has substantial implications for their personal management and that of their relatives. Unfortunately, in most countries, routine implementation of BRCA testing for ovarian cancer patients has been inconsistent and largely unsuccessful. We developed a rapid, robust, mainstream genetic testing pathway in which testing is undertaken by the trained cancer team with cascade testing to relatives performed by the genetics team. 207 women with ovarian cancer were offered testing through the mainstream pathway. All accepted. 33 (16%) had a BRCA mutation. The result informed management of 79% (121/154) women with active disease. Patient and clinician feedback was very positive. The pathway offers a 4-fold reduction in time and 13-fold reduction in resource requirement compared to the conventional testing pathway. The mainstream genetic testing pathway we present is effective, efficient and patient-centred. It can deliver rapid, robust, large-scale, cost-effective genetic testing of BRCA1 and BRCA2 and may serve as an exemplar for other genes and other diseases