ALBERT

Description: Alexander Russell , Anthony Yeates and Jonathan Eastwood review the state of the art and interesting future directions in this developing field, drawing on the RAS discussion meeting held on 12 December 2014.

Description: Perinatal distress and depression can have significant impacts on both the mother and baby. The present study investigated psychosocial and obstetric factors associated with perinatal distress and depressive symptoms among culturally and linguistically diverse (CALD) Australian women in Sydney, New South Wales. The study used retrospectively linked maternal and child health data from two Local Health Districts in Australia (N = 25,407). Perinatal distress was measured using the Edinburgh Postnatal Depression Scale (EPDS, scores of 10–12) and depressive symptoms, with EPDS scores of 13 or more. Multivariate multinomial logistic regression models were used to investigate the association between psychosocial and obstetric factors with perinatal distress and depressive symptoms. The prevalence of perinatal distress and depressive symptoms among CALD Australian women was 10.1% for antenatal distress; 7.3% for antenatal depressive symptoms; 6.2% for postnatal distress and 3.7% for postnatal depressive symptoms. Antenatal distress and depressive symptoms were associated with a lack of partner support, intimate partner violence, maternal history of childhood abuse and being known to child protection services. Antenatal distress and depressive symptoms were strongly associated with postnatal distress and depressive symptoms. Higher socioeconomic status had a protective effect on antenatal and postnatal depressive symptoms. Our study suggests that current perinatal mental health screening and referral for clinical assessment is essential, and also supports a re-examination of perinatal mental health policy to ensure access to culturally responsive mental health care that meets patients’ needs.

Description: We describe advanced spectral and radiometric calibration techniques developed for NASA’s Next Generation Airborne Visible Infrared Imaging Spectrometer (AVIRIS-NG). By employing both statistically rigorous analysis and utilizing in situ data to inform calibration procedures and parameter estimation, we can dramatically reduce undesirable artifacts and minimize uncertainties of calibration parameters notoriously difficult to characterize in the laboratory. We describe a novel approach for destriping imaging spectrometer data through minimizing a Markov Random Field model. We then detail statistical methodology for bad pixel correction of the instrument, followed by the laboratory and field protocols involved in the corrections and evaluate their effectiveness on historical data. Finally, we review the geometric processing procedure used in production of the radiometrically calibrated image data.

Description: Ice cream is a complex multi-phase colloidal soft-solid and its three-dimensional microstructure plays a critical role in determining the oral sensory experience or mouthfeel. Using in-line phase contrast synchrotron X-ray tomography, we capture the rapid evolution of the ice cream microstructure during heat shock conditions in situ and operando, on a time scale of minutes. The further evolution of the ice cream microstructure during storage and abuse was captured using ex situ tomography on a time scale of days. The morphology of the ice crystals and unfrozen matrix during these thermal cycles was quantified as an indicator for the texture and oral sensory perception. Our results reveal that the coarsening is due to both Ostwald ripening and physical agglomeration, enhancing our understanding of the microstructural evolution of ice cream during both manufacturing and storage. The microstructural evolution of this complex material was quantified, providing new insights into the behavior of soft-solids and semi-solids, including many foodstuffs, and invaluable data to both inform and validate models of their processing.

Description: The Large-aperture Experiment to Detect the Dark Age (LEDA) was designed to detect the predicted O(100) mK sky-averaged absorption of the cosmic microwave background by hydrogen in the neutral pre- and intergalactic medium just after the cosmological Dark Age. The spectral signature would be associated with emergence of a diffuse Lyα background from starlight during ‘Cosmic Dawn’. Recently, Bowman et al. have reported detection of this predicted absorption feature, with an unexpectedly large amplitude of 530 mK, centred at 78 MHz. Verification of this result by an independent experiment, such as LEDA, is pressing. In this paper, we detail design and characterization of the LEDA radiometer systems, and a first-generation pipeline that instantiates a signal path model. Sited at the Owens Valley Radio Observatory Long Wavelength Array, LEDA systems include the station correlator, five well-separated redundant dual polarization radiometers and back-end electronics. The radiometers deliver a 30–85 MHz band (16 〈z 〈 34) and operate as part of the larger interferometric array, for purposes ultimately of in situ calibration. Here, we report on the LEDA system design, calibration approach, and progress in characterization as of 2016 January. The LEDA systems are currently being modified to improve performance near 78 MHz in order to verify the purported absorption feature.

Description: Abstract 4306 VOD is a serious and potentially life-threatening complication of HPCT as a result of liver injury from the effect of chemotherapy and/or radiation. The reported incidence rate in pediatric HPCT patients varies widely from 5% to 40%. Previous studies have shown the beneficial effects of post-transplant pharmacological therapies such as ursodeoxyholic acid (ursodiol), heparin, and defibrotide at preventing VOD. However, the combined effect of heparin and ursodiol prophylaxis in preventing VOD in pediatric patients has yet to be determined. This study evaluated retrospectively whether there was a benefit of such combined therapy in pediatric HPCT patients. Our center adopted as standard practice for all HPCT patients the initiation of low dose heparin at 4 units/kg/hour with the commencement of conditioning for HPCT until day +28 post transplant. In 2003, we combined ursodiol 10 mg/kg TID to start with HPCT conditioning and to continue until day + 100 post transplant with low dose heparin through day + 28 for all pediatric HPCT patients. We performed a retrospective chart review and compared the characteristics and the incidence of VOD in patients who underwent transplantation from 1996-2002 and received heparin alone compared to 2003-2008 when the patients received the combination of heparin and ursodiol prophylaxis. Patients were identified through medical records with the ICD diagnosis of VOD. The medical records were reviewed and those patients who did not meet the Baltimore criteria for the diagnosis of VOD were excluded. Only patients who developed VOD with their first transplants were included. Group I = Heparin (216) Group II = Heparin + Ursodiol (220) Allogeneic 187 (86.5%) 160 (72.7%) Autologous 29 (13.5%) 60 (27.3%) Median Age 9 yrs 8 yrs Male 123 (57%) 135 (62%) Female 93 (43%) 85 (38%) Non-malignant 34 (15.7%) 50 (22.8%) Hematologic malignancy 143 (66.2%) 109 (49.5%) Non-hematologic malignancy 39 (18.1%) 61 (27.7%) # VOD 13 5 The 100 day incidence of VOD was 0.0605 (SE 0.01618) in group 1 and 0.0227 (SE 0.01002) in group 2. The difference is 0.0377 (SE 0.0190) and based on a standard normal distribution with a p = 0.0473. The estimated risk of VOD for patients receiving Heparin + Ursodiol is 0.94 (risk or hazard ratio) that of the risk with Heparin alone, with a 95% confidence interval of (0.918, 0.960). This represents about a 6% reduction in risk for those receiving Heparin + Ursodiol. The day 100 survival in the VOD patients was 6 out of 13 in group 1 and 3 out of 5 in group 2. In conclusion, low dose heparin and ursodiol prophylaxis appears to be an effective strategy in VOD prevention in pediatric patients. The combination appeared to be more effective than heparin alone. However, this study is limited in that it is retrospective in nature. Disclosures: Off Label Use: heparin and ursodiol as VOD prophylaxis.

Description: Background: In both the novel and pre-novel agents era, high dose therapy followed by autologous hematopoietic cell transplant (AHCT) has been shown to prolong survival in multiple myeloma (MM) in randomized trials, but prospective have only included younger patients (65 -70 years and younger). Given that the median age at diagnosis of MM is 66 years, it is important to know the outcomes of AHCT in older patients. Similarly, the definite outcomes of AHCT in very young patients (70 years; N=105) and young (≤50 years, N=86) and compared the outcomes. The primary objectives were to assess overall survival (OS), progression free survival, (PFS), and non-relapse mortality (NRM) in these two groups. Results: Eighty-sex patients were young (≤50 years), while 105 patients were old (〉70 years). Young patients had better performance status and lower co-morbidity index, while majority of older cohort received dose reduced high dose melphalan between 140-180 mg/m2. Median follow up of survivors in the younger cohort was 33 months (range, 2-164) compared to the 22.5 months (3-133) in the old group (p=0.02). The PFS at 1 year was 60% (95%CI 46-72) for young patients and 58 (95%CI, 45-69) for the old ones. The OS at 1 year was 92% (95% CI 84-96) for younger and 85% (95% CI 76-91) for the older cohorts. On multivariate analysis, age did not have any effect on survival (p =0.82), high-risk cytogenetics (HR 2.2, 95% CI 1.06-4.6, p=0.04) was associated with higher mortality. High-risk cytogenetics (HR 1.2, 95% CI 1.1-3.5, p=0.004) and non-responding or progressive disease at transplantation (HR, 5.0 95% CI 1.8-13.5, p=0.02) were significantly associated with inferior PFS. Conclusion: Age by itself should not be a limiting factor in considering the modality of AHCT. However consideration could be given to augmenting therapy for young patients with additional novel treatments post transplant given their similar outcomes with the old patients based on our study. Overall survival between the two age groups, 1: 〉70 years old and 2: ≤50 years old. Overall survival between the two age groups, 1: 〉70 years old and 2: ≤50 years old. Figure Figure. Disclosures Hamadani: Takeda: Research Funding. Hari:Merck: Research Funding; BMS: Honoraria.

Description: Key Points Blockade of IL-27 signaling mitigates the severity of GVHD by recalibrating the effector and regulatory arms of the immune system. Inhibition of IL-27 augments the reconstitution of CD4+ and CD8+ regulatory T cells and increases the stability of Foxp3 expression.

Description: Antibodies (abs) specific for heparin/platelet factor 4 (H/PF4) complexes are a hallmark of heparin-induced thrombocytopenia and thrombosis (HIT) and are thought to play a role in predisposing patients to thrombocytopenia and thrombosis. A solid phase assay that uses H/PF4 complexes as targets for ab detection (PF4 ELISA) is almost invariably positive in patients with HIT. This test can be performed quickly and a negative result makes HIT very unlikely; however, many patients testing positive in this assay do not develop HIT. A second test, the serotonin release assay (SRA), considered the "gold standard" for HIT diagnosis, selectively detects HIT abs that activate platelets and are presumptively pathogenic. A positive SRA test correlates well with clinical HIT but the SRA is technically demanding and is routinely performed only by a few reference laboratories, precluding its use for early patient diagnosis and management. This can have adverse consequences since both over- and under-diagnosis of HIT can have serious medical and economic impact. We recently showed that platelet-activating HIT abs preferentially recognize PF4 bound to platelet glycosaminoglycans in the absence of heparin (Blood 2015; 125(1): 155-61). Based on this finding we developed a technically simple assay (PF4-dependent p-selectin expression assay [PEA]) for detection of platelet-activating HIT abs. In the PEA, target platelets are first "primed" for activation by being incubated with PF4 and are then exposed to patient serum. P-selectin expression (percent of maximum) is measured as an indicator of platelet activation (Thromb Haemost. 2015; 114(5) epub). Specificity of a positive test result is confirmed by inhibition with high dose heparin (HDH). To compare diagnostic performance of the PEA and the SRA, 91 sera from patients referred for HIT testing who had been assigned clinical scores for HIT ("4T scores") ranging from 0 to 8 (low to high likelihood of HIT, respectively) were tested in both assays. Samples from patients with Intermediate or High 4T scores (4-8) and PF4 ELISA OD values 〉1.0 were considered "HIT-positive " given that neither criterion by itself has a high positive predictive value for HIT. Intermediate to High 4T-scored patients with PF4 ELISA ODs 24% p-selectin expression. For this analysis, a sample was considered PEA-positive if p-selectin expression was 〉24%, and inhibited 〉50% with HDH. Results are shown in Fig 1. The apparent superiority of the PEA over the SRA for identifying HIT-positive patients suggested that the PEA might be intrinsically more sensitive than the SRA for detecting platelet activating abs. This was confirmed by testing serial dilutions of 3 arbitrarily selected High-4T HIT abs against identical target platelets. A representative result is shown in Fig 2. The many attractive features of the PEA, especially its technical simplicity and its ability to identify patients judged to have a high likelihood of HIT suggest that its use can facilitate early diagnosis and improve management of this diagnostically challenging disorder. In Figures 1 and 2, the solid and dotted lines represent positive cut-offs of the SRA and PEA, respectively. Figure 1. Thirty patients judged to be HIT-positive were tested in the PEA and SRA. The PEA was positive in 27 and the SRA in 16. Fig 1B. The PEA was positive in 8 and the SRA in 3 among 61 HIT-negative patients. The two assays had similar specificity (87% [PEA] vs. 95% [SRA]; p=ns), however, the PEA had significantly higher diagnostic sensitivity than the SRA (90% [PEA] vs. 53% [SRA]; p

Description: Summary We present software to characterize and rank potential therapeutic (drug) targets with data from public databases and present it in a user-friendly format. By understanding potential obstacles to drug development through the gathering and understanding of this information, combined with robust approaches to target validation to generate therapeutic hypotheses, this approach may provide high quality targets, leading the process of drug development to become more efficient and cost-effective. Availability and implementation The information we gather on potential targets concerns small-molecule druggability (ligandability), suitability for large-molecule approaches (e.g. antibodies) or new modalities (e.g. antisense oligonucleotides, siRNA or PROTAC), feasibility (availability of resources such as assays and biological knowledge) and potential safety risks (adverse tissue-wise expression, deleterious phenotypes). This information can be termed ‘tractability’. We provide visualization tools to understand its components. TractaViewer is available from https://github.com/NeilPearson-Lilly/TractaViewer Supplementary information Supplementary data are available at Bioinformatics online.