Commensurate Priors on a Finite Mixture Model for Incorporating Repository Data in Clinical Trials

Docosahexaenoic acid (DHA) is a good source of fat that can be taken up through food, such as fish, or taken as a supplement. Evidence is building that DHA provides a high-yield, low-risk strategy to reduce preterm birth and/or low birth weight. These births are great costs to society. A recently completed Phase III trial revealed that higher birth weight and gestational age were associated with DHA dosed at 600 mg/day. In this article, we take a posterior predictive approach to assess impacts of these findings on public health. Simple statistical models are not adequate for accurate posterior predictive distribution estimation. Of particular interest is that the joint distribution of birth weight and gestational age is well modeled by a finite mixture of three normal distributions. Data from our own clinical trial exhibit similar features. Using the mean and variance-covariance matrices from a previous study and flexible commensurate priors for the mixing parameters, we estimate the effect of DHA supplementation on over 20,000 infants born in hospitals demographically similar to the hospital where the clinical trial was conducted

Blood and marrow transplantation compensation: Perspective in payer and provider relations

AbstractThe high cost per patient of hematopoietic cell transplantation (HCT) causes this therapy to be the focus of much controversy, given the competing societal demands to provide all possible therapy to preserve life while simultaneously limiting global health care expenditures. Treatment and eligibility decisions for HCT often are heavily scrutinized by both governmental and private payers and not simply determined by physicians, facility providers, and the patient. In an effort to control costs, payers have administrative infrastructure to review resource utilization by these patients. Additionally payers have developed payment methodologies, usually in the form of a case rate payment structure, that place facilities and physician providers of HCT at financial risk for adverse patient financial outcomes in an effort to promote optimal utilization and selection of patients for HCT. As providers enter into such financial risk arrangements with payers, the providers need to understand the true cost of care and be able to identify predictable and unpredictable outlier risks for the financial consequences of medical complications. HCT providers try to protect themselves from excessive financial risk by having different payment rates for different types of transplant, eg, autologous versus HLA or genotypically matched related versus HLA mismatched transplants. Because at certain times in the HCT process risk is more unpredictable, HCT providers require different payment system strategies for the different time periods of care such as evaluation, pre-transplant disease management, harvesting, and cell processing, as well as short- and long-term follow-up. Involvement by clinicians is essential for this process to be done well, especially given the rapid changes technological innovation brings to HCT. Constant dialogue and interaction between providers and payers on these difficult financial issues with HCT is essential to preserve patient access to this potentially lifesaving therapy

Self-supporting graphene films and their applications

The self-supporting monolayer material which is graphene has excited enormous interest over the ten years since its discovery due to its remarkable electrical, mechanical thermal and chemical properties. In this paper we describe our work to develop chemical vapour deposition methods to grow monolayer graphene on copper foil substrates and the subsequent transfer process. Raman microscopy, scanning electron microscopy and atomic force microscopy (AFM) are used to examine the quality of the transferred material. To demonstrate the process we describe transfer onto patterned SiO2/Si substrates which forms freely suspended graphene with focus on circular wells forming graphene drums. These show interesting mechanical properties which are being explored as nanomechanical resonators.UK NMS Programme, the EU EMRP (European Metrology Research Programme) projects MetNEMS and GraphOh

Maternal Docosahexaenoic Acid Exposure Needed to Achieve Maternal–Newborn EQ

Achieving maternal docosahexaenoic acid (DHA) status equal to or greater than the infant’s DHA status at delivery is known as maternal–newborn DHA equilibrium (EQ) and is thought to be important for optimizing newborn DHA status throughout infancy. The objective of this study was to determine the daily DHA intake during pregnancy most likely to result in EQ. The participants (n = 1145) were from two randomized control trials of DHA supplementation in pregnancy. DHA intake was estimated using an abbreviated food frequency questionnaire. Total DHA exposure during pregnancy was calculated as a weighted average of the estimated DHA intake throughout pregnancy and the randomized DHA dose (200, 800, 1000 mg). Red blood cell DHA was measured from maternal and cord blood plasma at delivery and EQ status was calculated. The DHA intake required to achieve EQ was estimated by regression. In terms of DHA exposure, the point estimate and 95% confidence interval to achieve EQ was 643 (583, 735) mg of DHA/day. The results of our trial suggest an intake of 650 mg of DHA/day is necessary to increase the potential for EQ at delivery. The clinical benefits of achieving EQ deserves continued study

C-axis Josephson Tunneling Between YBCO and Pb: Direct Evidence for Mixed Order Parameter Symmetry in a High-T_c Superconductor

We report a new class of $c$-axis Josephson tunneling experiments in which a conventional superconductor (Pb) is deposited across a single twin boundary of a YBa_2Cu_3O_{7-\delta} crystal. We measure the critical current as a function of magnitude and angle of magnetic field applied in the plane of the junction. In all samples, we observe a clear experimental signature of an order parameter phase shift across the twin boundary. These results provide strong evidence for mixed $d$- and $s$-wave pairing in YBCO, with a reversal in the sign of the $s$-wave component across the twin boundary.Comment: 4 pages RevTex, 4 postscript figures included, submitted to Phys. Rev. Let

Light-driven chloride transport kinetics of halorhodopsin

Despite growing interest in light-driven ion pumps for use in optogenetics, current estimates of their transport rates span two orders of magnitude due to challenges in measuring slow transport processes and determining protein concentration and/or orientation in membranes in vitro. In this study, we report, to our knowledge, the first direct quantitative measurement of light-driven Cl transport rates of the anion pump halorohodopsin from Natronomonas pharaonis (NpHR). We used light-interfaced voltage clamp measurements on NpHR-expressing oocytes to obtain a transport rate of 219 (± 98) Cl /protein/s for a photon flux of 630 photons/protein/s. The measurement is consistent with the literature-reported quantum efficiency of ∼30% for NpHR, i.e., 0.3 isomerizations per photon absorbed. To reconcile our measurements with an earlier-reported 20 ms rate-limiting step, or 35 turnovers/protein/s, we conducted, to our knowledge, novel consecutive single-turnover flash experiments that demonstrate that under continuous illumination, NpHR bypasses this step in the photocycle

GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia.

We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P \u3c .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P \u3c .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors. © 2019 American Society of Hematology. All rights reserved

Linked within-host and between-host models and data for infectious diseases: a systematic review

The observed dynamics of infectious diseases are driven by processes across multiple scales. Here we focus on two: within-host, that is, how an infection progresses inside a single individual (for instance viral and immune dynamics), and between-host, that is, how the infection is transmitted between multiple individuals of a host population. The dynamics of each of these may be influenced by the other, particularly across evolutionary time. Thus understanding each of these scales, and the links between them, is necessary for a holistic understanding of the spread of infectious diseases. One approach to combining these scales is through mathematical modeling. We conducted a systematic review of the published literature on multi-scale mathematical models of disease transmission (as defined by combining within-host and between-host scales) to determine the extent to which mathematical models are being used to understand across-scale transmission, and the extent to which these models are being confronted with data. Following the PRISMA guidelines for systematic reviews, we identified 24 of 197 qualifying papers across 30 years that include both linked models at the within and between host scales and that used data to parameterize/calibrate models. We find that the approach that incorporates both modeling with data is under-utilized, if increasing. This highlights the need for better communication and collaboration between modelers and empiricists to build well-calibrated models that both improve understanding and may be used for prediction

Using participatory action research to empower district hospital staff to deliver quality-assured essential surgery to rural populations in Malawi, Zambia, and Tanzania

BackgroundIn 2017 the SURG-Africa project set out to institute a surgical, obstetric, trauma and anesthesia (SOTA) care capacity-building intervention focused on non-specialist providers at district hospitals in Zambia, Malawi and Tanzania. The aim was to scale up quality-assured SOTA care for rural populations. This paper reports the process of developing the intervention and our experience of initial implementation, using a participatory approach.MethodsParticipatory Action Research workshops were held in the 3 countries in July–October 2017 and in October 2018–July 2019, involving representatives of key local stakeholder groups: district hospital (DH) surgical teams and administrators, referral hospital SOTA specialists, professional associations and local authorities. Through semi-structured discussions, qualitative data were collected on participants’ perceptions and experiences of barriers to the provision of SOTA care at district level, and on the training and supervision needs of district surgical teams. Data were compared for themes across countries and across surgical team cadres.ResultsAll groups reported a lack of in-service training to develop essential skills to manage common SOTA cases; use and care of equipment; essential anesthesia care including resuscitation skills; and infection prevention and control. Very few district surgical teams had access to supervision. SOTA providers at DHs reported a demand for more feedback on referrals. Participants prioritized training needs that could be addressed through regular in-service training and supervision visits from referral hospital specialists to DHs. These data were used by participants in an action-planning cycle to develop site-specific training plans for each research site.ConclusionThe inclusive, participatory approach to stakeholder involvement in SOTA system strengthening employed by this study supported the design of a locally relevant and contextualized intervention. This study provides lessons on how to rebalance power dynamics in Global Surgery, through giving a voice to district surgical teams