Goal-directed or goal-misdirected - how should we interpret the literature?

Goal-directed therapy (GDT) can be a vague term, meaning different things to different people and, depending on the clinical environment, sometimes even different things to the same person. It can refer to perioperative fluid management, clinicians driving oxygen delivery to supramaximal values, early treatment of sepsis in the emergency department, and even to restriction of perioperative crystalloids with the goal of maintaining preadmission body weight. Understandably, strong opinions about GDT vary; some clinicians consider it essential for perioperative care, others completely ineffective in critically ill patients. This commentary aims to further position the excellent review by Lees and colleagues in the context of the critical care and perioperative setting

A fluid biomarker reveals loss of TDP-43 splicing repression in presymptomatic ALS-FTD

Although loss of TAR DNA-binding protein 43 kDa (TDP-43) splicing repression is well documented in postmortem tissues of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), whether this abnormality occurs during early-stage disease remains unresolved. Cryptic exon inclusion reflects loss of function of TDP-43, and thus detection of proteins containing cryptic exon-encoded neoepitopes in cerebrospinal fluid (CSF) or blood could reveal the earliest stages of TDP-43 dysregulation in patients. Here we use a newly characterized monoclonal antibody specific to a TDP-43-dependent cryptic epitope (encoded by the cryptic exon found in HDGFL2) to show that loss of TDP-43 splicing repression occurs in ALS-FTD, including in presymptomatic C9orf72 mutation carriers. Cryptic hepatoma-derived growth factor-like protein 2 (HDGFL2) accumulates in CSF at significantly higher levels in familial ALS-FTD and sporadic ALS compared with controls and is elevated earlier than neurofilament light and phosphorylated neurofilament heavy chain protein levels in familial disease. Cryptic HDGFL2 can also be detected in blood of individuals with ALS-FTD, including in presymptomatic C9orf72 mutation carriers, and accumulates at levels highly correlated with those in CSF. Our findings indicate that loss of TDP-43 cryptic splicing repression occurs early in disease progression, even presymptomatically, and that detection of the HDGFL2 cryptic neoepitope serves as a potential diagnostic biomarker for ALS, which should facilitate patient recruitment and measurement of target engagement in clinical trials

Documentation of the INDOT Experience and Construction of the Bridge Decks Containing Internal Curing in 2013

The Indiana Department of Transportation (INDOT) constructed four bridge decks utilizing internally cured, high performance concrete (IC HPC) during the summer of 2013. These decks implement research findings from the research presented in the FHWA/IN/JTRP-2010/10 report where internal curing was proposed as one method to reduce the potential for shrinkage cracking, leading to improved durability. The objective of this research was to document the construction of the four IC HPC bridge decks that were constructed in Indiana during 2013 and quantify the properties and performance of these decks. This report contains documentation of the production and construction of IC HPC concrete for the four bridge decks in this study. In addition, samples of the IC HPC used in construction were compared with a reference high performance concrete (HPC) which did not utilize internal curing. These samples were transported to the laboratory where the mechanical properties, resistance to chloride migration, and potential for shrinkage and cracking was assessed. Using experimental results and mixture proportions, the diffusion based service life of the bridge decks was able to be estimated. Collectively, the results indicate that the IC HPC mixtures that were produced as a part of this study exhibit the potential to more than triple the service life of the typical bridge deck in Indiana while reducing the early age autogenous shrinkage by more than 80% compared to non-internally cured concretes

Near-infrared line identification in type Ia supernovae during the transitional phase

We present near-infrared synthetic spectra of a delayed-detonation hydrodynamical model and compare them to observed spectra of four normal type Ia supernovae ranging from day +56.5 to day +85. This is the epoch during which supernovae are believed to be undergoing the transition from the photospheric phase, where spectra are characterized by line scattering above an optically thick photosphere, to the nebular phase, where spectra consist of optically thin emission from forbidden lines. We find that most spectral features in the near-infrared can be accounted for by permitted lines of Fe II and Co II. In addition, we find that [Ni II] fits the emission feature near 1.98 {\mu}m, suggesting that a substantial mass of 58Ni exists near the center of the ejecta in these objects, arising from nuclear burning at high density. A tentative identification of Mn II at 1.15 {\mu}m may support this conclusion as well.Comment: accepted to Ap

LCF Life of NiCr-Y Coated Disk Alloys After Shot Peening, Oxidation and Hot Corrosion

In a prior companion study (Ref. 1), three different Ni-Cr coating compositions (29, 35.5, 45 wt% Cr) were applied at two thicknesses by Plasma Enhanced Magnetron Sputtering (PEMS) to two similar Ni-based disk alloys. One coating also received a thin ZrO2 overcoat. The low cycle fatigue (LCF) life of each coating was determined at 760 C and was less than that of the uncoated specimens. In this followon effort, shot peening was examined as a means to improve the as-deposited coating morphology as well as impart a residual compressive stress in the near-surface region. After evaluating the effect of the shot peening on the LCF life, the effectiveness of the shot-peened coating in protecting the disk alloy from oxidation and hot corrosion attack was evaluated. This evaluation was accomplished by exposing coated and shot-peened specimens to 500 h of oxidation followed by 50 h of hot corrosion, both at 760 C in air. These exposed specimens were then tested in fatigue and compared to similarly treated and exposed uncoated specimens. For all cases, shot peening improved the LCF life of the coated specimens. More specifically, the highest Cr coating showed the best LCF life of the coated specimens after shot peening, as well as after the environmental exposures. Characterization of the coatings after shot peening, oxidation, hot corrosion and LCF testing is presented and discussed

Improving the validity of activity of daily living dependency risk assessment

OBJECTIVES: Efforts to prevent activity of daily living (ADL) dependency may be improved through models that assess older adults' dependency risk. We evaluated whether cognition and gait speed measures improve the predictive validity of interview-based models. METHOD: Participants were 8,095 self-respondents in the 2006 Health and Retirement Survey who were aged 65 years or over and independent in five ADLs. Incident ADL dependency was determined from the 2008 interview. Models were developed using random 2/3rd cohorts and validated in the remaining 1/3rd. RESULTS: Compared to a c-statistic of 0.79 in the best interview model, the model including cognitive measures had c-statistics of 0.82 and 0.80 while the best fitting gait speed model had c-statistics of 0.83 and 0.79 in the development and validation cohorts, respectively. CONCLUSION: Two relatively brief models, one that requires an in-person assessment and one that does not, had excellent validity for predicting incident ADL dependency but did not significantly improve the predictive validity of the best fitting interview-based models

Efficiency of TTAC's ORTEC IDM

ORNL's Technical Testing and Analysis Center (TTAC) acquired a High Purity Germanium Detector (HPGe) from ORTEC - a variant called an Interchangeable Detection Module (IDM). This detector has excellent energy resolution as well as high intrinsic efficiency. The purpose of this report is to detail the determination of the efficiency curve of the IDM, so future measurements can quantify the (otherwise unknown) activity of sources. Without such a curve, the activity cannot be directly reported by use of the IDM alone - a separate device such as an ion chamber would be required. This builds upon the capability of TTAC. The method for determining the energy-dependent intrinsic efficiency is laid-out in this report. It's noteworthy that this basic technique can be applied to any spectroscopic radiation detector, independent of the specific type (e.g. NaI, CzT, ClYC)

Early Detection Rapid Response Program Targets New Noxious Weed Species in Washington State

Early detection, rapid response is a critical component of invasive plant management. It can be challenging, however, to detect new invaders before they become established if landowners cannot identify species of concern. In order to increase awareness, eye-catching postcards were developed in Washington State as part of a noxious weed educational campaign. Plant identification, potential impacts, and current distributions are provided in a simple format for easy information consumption. Postcards are distributed across the state at various venues, thereby increasing the general public\u27s exposure to little known but high risk species