Evaluation of the infant at risk for neurodevelopmental disability

Background. Infants with neurodevelopmental abnormality need to start therapy early, and because of this they should be detected as soon as possible. Currently, no widely accepted method of early evaluation exists.Objectives_ To assess and compare, in terms of predicting neurodevelopmental outcome at 1 year of age: (i) a perinatal risk rating (PRR); (ii) the DubQwitz Neurological Assessment. (DNA); and (iii) the Infant Neuromotor Assessment (INA). Design and setting. A prospective neurodevelopmental followup study on graduates from the Groote Schuur Hospital (GSH) neonatal intensive care unit (NICU). Subjects. A cohort of 130 consecutive NICD graduates were selected according to high-risk criteria_Outcome measures. Each infant was examined at term gestational age on the DNAbefore discharge, and a PRR was allocated_ Study infants were seen again at 18 weeks of age when an INA was done, and at 1 year of age a Griffiths Developmental Assessment and full neurological examination was carried out.Results. All of the 130 infants assessed at term were seen at 18 weeks. Thereafter 5 were lost to follow-up and 2 died. The outcome for the remaining 123 is known.Conclusions. Prediction of a normal outcome at 1 year of age was 96% on the DNA and 98% for the PRR, but for an abnormal outcome they predicted only 56% and 42%, respectively. The INA done at 18 weeks predicted a normal outcome at 1 year in 99% of cases if 3 or less abnormal signs were present and an abnormal outcome in 82% of cases with 4 or more abnormal signs. Based on these findings a protocol for follow-up of these high-risk infants is suggested

Power output estimation of a RM3 WEC with HF radar measured complex representative sea states

Wave tank model testing has been widely used to assess the performance of Wave Energy Converters (WEC) in different technology readiness levels (TRL). At early stage the use of simple wave conditions such as regular waves and parametric wave spectrum JONSWAP or Pierson-Moskowitz spectrum is acceptable. However at later stages there is a need to use site specific complex wave conditions representative of potential prototype deployment sites. In previous research, 10 different regrouping methods on HF radar measured wave spectrum were tested to find out the most representative sea states for tank testing. It has been shown that by using the K-means clustering technique, the characteristics of wave conditions can be well preserved [1, 2]. In order to assess the power capture performance of a typical WEC in these representative sea states, the RM3 point absorber has been simulated. By analysing how well the average power output predicted from different representative sea-state selection methods compares with the total power output prediction, it is shown that the non-directional wave spectrum K-means clustering method provides the most representative sea states and, for a point absorber, with a very accurate estimation of the total power output, which is not the case by using a traditional binning method. The importance of using the complex site-specific sea states rather than simplified parametric JONSWAP sea states to obtain the accurate total power estimation has also been shown

Repurposing tofacitinib as an anti-myeloma therapeutic to reverse growth-promoting effects of the bone marrow microenvironment.

The myeloma bone marrow microenvironment promotes proliferation of malignant plasma cells and resistance to therapy. Activation of JAK/STAT signaling is thought to be a central component of these microenvironment-induced phenotypes. In a prior drug repurposing screen, we identified tofacitinib, a pan-JAK inhibitor Food and Drug Administration (FDA) approved for rheumatoid arthritis, as an agent that may reverse the tumor-stimulating effects of bone marrow mesenchymal stromal cells. Herein, we validated in vitro, in stromal-responsive human myeloma cell lines, and in vivo, in orthotopic disseminated xenograft models of myeloma, that tofacitinib showed efficacy in myeloma models. Furthermore, tofacitinib strongly synergized with venetoclax in coculture with bone marrow stromal cells but not in monoculture. Surprisingly, we found that ruxolitinib, an FDA approved agent targeting JAK1 and JAK2, did not lead to the same anti-myeloma effects. Combination with a novel irreversible JAK3-selective inhibitor also did not enhance ruxolitinib effects. Transcriptome analysis and unbiased phosphoproteomics revealed that bone marrow stromal cells stimulate a JAK/STAT-mediated proliferative program in myeloma cells, and tofacitinib reversed the large majority of these pro-growth signals. Taken together, our results suggest that tofacitinib reverses the growth-promoting effects of the tumor microenvironment. As tofacitinib is already FDA approved, these results can be rapidly translated into potential clinical benefits for myeloma patients

Technical Equivalency Documentation for a Newly Aquired Alpha Spectroscopy System

The response of a recently acquired Canberra{trademark} Alpha Analyst 'Blue' system (Chamber Number's 173-208) used by the Hazards Control, Radiation Safety Section, WBC/Spectroscopy Team has been studied with respect to an existing Canberra system. The existing Canberra system consists of thirty Alpha Analyst dual chambers Model XXXX comprising a total of sixty detectors (Chambers Number's 101-124 and 137-172). The existing chambers were previously compared to an older system consisting of thirty-six Model 7401 alpha spectrometry chambers (Chamber Number's 1-36) Chambers 101-124 and 137-172 are DOELAP accredited. The older system was previously DOELAP accredited for the routine Alpha Spectroscopy program used in LLNL's in vitro bioassay program. The newly acquired Alpha Analyst system operates on a network with software that controls and performs analysis of the current Alpha Analyst system (Chamber Number's 101-124 and 137-172). This exact same software is used for the current system and the newly acquired system and is DOELAP accredited. This document compares results from the existing Alpha System with the newer Alpha Analyst system

Trends in floating offshore wind platforms: A review of early-stage devices

This study reviews early-stage floating offshore wind turbine (FOWT) platform designs. The review covers 86 past and current early-stage platform designs, ranging from early conceptual designs to platforms which have undergone lab tests simulating extreme conditions. The evolution of FOWT platforms is described, and it is shown how FOWT platforms were originally influenced by floating platforms typically used in the oil and gas industry, but FOWT platforms have deviated away from these conventional floater designs to suit the specific needs of the technology. Four phases are defined to characterize chronological shifts in design thinking. There has been a number of alternative cost reduction strategies recently, including (i) specializing the platform to a particular location or environment, (ii) increasing manufacturability, and (iii) designing an innovative platform which diverges further from conventional designs. For the latter strategy, there has been an emergence of multi-turbine platforms, hybrid platforms, platforms which use a combination of stability mechanisms, and hydrodynamically specialized platforms. Finally, potential future trends are discussed, and it is shown that competing priorities for platform designers in the future will likely mean that the design space must compromise between increasing standardization and increasing specialization

Effect of the Current-Wave Angle on the Local Scour around Circular Piles

This paper studies the effect of the wave front-current angle on the scour around a circular pile. An experimental study was carried out in the Coastal, Ocean and Sediment Transport (COAST) laboratory at the University of Plymouth (UK) using a single monopile of 0.125 m in diameter and an 8 m long by 1.5 m wide by 0.2 m high sand pit. The results obtained during the test campaign show the influence of the angle between waves and currents on both the maximum scour depth and the time scale of the process. Wave fronts partially aligned with current (65°) produce deeper scour holes than perpendicular forcing conditions (90°). Wave fronts partially against the current (115°) produce less scour than any of the two previous scenarios. The addition of waves reduced the maximum scour depth, compared with the current-only case. The development of the scour hole was found to be more rapid when waves are added to the current, with 50% of the final scour achieved in half the time. The results show that wave direction relative to the current is an important component in scour prediction

Enhancement of mercury control in flue-gas cleanup systems

This paper summarizes research at Argonne National Laboratory which is focused on techniques to enhance the capture of elemental mercury and integrate its control into existing flue-gas cleanup (FGC) systems. Both laboratory and field tests have shown that very little elemental mercury is captured in a wet scrubber system due to the low solubility of that species. To enhance the ability of wet scrubbers to capture mercury, Argonne has studied improved mass transfer through both mechanical and chemical means, as well as the conversion of elemental mercury into a more soluble species that can be easily absorbed. Current research is investigating the roles of several halogen species either alone or in combination with typical flue-gas components such as sulfur dioxide and nitric oxide in the oxidation of mercury to form compounds that are easily scrubbed from the flue gas

Clcn7F318L/+ as a new mouse model of Albers-Schönberg disease

Dominant negative mutations in CLCN7, which encodes a homodimeric chloride channel needed for matrix acidification by osteoclasts, cause Albers-Schönberg disease (also known as autosomal dominant osteopetrosis type 2). More than 25 different CLCN7 mutations have been identified in patients affected with Albers-Schönberg disease, but only one mutation (Clcn7G213R) has been introduced in mice to create an animal model of this disease. Here we describe a mouse with a different osteopetrosis-causing mutation (Clcn7F318L). Compared to Clcn7+/+ mice, 12-week-old Clcn7F318L/+ mice have significantly increased trabecular bone volume, consistent with Clcn7F318L acting as a dominant negative mutation. Clcn7F318L/F318L and Clcn7F318L/G213R mice die by 1 month of age and resemble Clcn7 knockout mice, which indicate that p.F318L mutant protein is non-functional and p.F318L and p.G213R mutant proteins do not complement one another. Since it has been reported that treatment with interferon gamma (IFN-G) improves bone properties in Clcn7G213R/+ mice, we treated Clcn7F318L/+ mice with IFN-G and observed a decrease in osteoclast number and mineral apposition rate, but no overall improvement in bone properties. Our results suggest that the benefits of IFN-G therapy in patients with Albers-Schönberg disease may be mutation-specific