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The Principal INvestigator Development and Resources (PINDAR) program was developed at the NYU-H+H Clinical and Translational Science Award (CTSA) hub in response to a perceived need for focused good clinical practice (GCP) training designed specifically for principal investigators (PIs) performing human subject research. PINDAR is a novel 6-hour, instructor lead, participatory, in-person course for PIs developed de novo, piloted, and implemented. One hundred and seventeen faculty PIs participated in PINDAR from November 2016 through September 2018. All obtained mutual recognition for ICH E6 GCP training from TransCelerate Biopharma. PINDAR was well received by participant PIs, and feedback surveys have revealed a high degree of satisfaction with the program. Other CTSA hubs and research-intensive health systems should consider adopting a similar course focused on GCP for PIs.
Early life nutrition and feeding practices are important modifiable determinants of subsequent obesity, yet little is known about the circadian feeding pattern of 12-month-old infants. We aimed to describe the 24-h feeding patterns of 12-month-old infants and examine their associations with maternal and infant characteristics. Mothers from a prospective birth cohort study (n 431) reported dietary intakes of their 12-month-old infants and respective feeding times using 24-h dietary recall. Based on their feeding times, infants were classified into post-midnight (00.00–05.59 hours) and pre-midnight (06.00–23.59 hours) feeders. Mean daily energy intake was 3234 (sd 950) kJ (773 (sd 227) kcal), comprising 51·8 (sd 7·8) % carbohydrate, 33·9 (sd 7·2) % fat and 14·4 (sd 3·2) % protein. Mean hourly energy intake and proportion of infants fed were lower during post-midnight than pre-midnight hours. There were 251 (58·2 %) pre-midnight and 180 (41·8 %) post-midnight feeders. Post-midnight feeders consumed higher daily energy, carbohydrate, fat and protein intakes than pre-midnight feeders (all P<0·001). The difference in energy intake originated from energy content consumed during the post-midnight period. Majority (n 173) of post-midnight feeders consumed formula milk during the post-midnight period. Using multivariate logistic regression with confounder adjustment, exclusively breast-feeding during the first 6 months of life was negatively associated with post-midnight feeding at 12 months (adjusted OR 0·31; 95 % CI 0·11, 0·82). This study provides new insights into the circadian pattern of energy intake during infancy. Our findings indicated that the timing of feeding at 12 months was associated with daily energy and macronutrient intakes, and feeding mode during early infancy.
We report here the first radiocarbon dating of blood residues on prehistoric stone tools. The residues found on two stone artifacts were subjected to various exploratory biochemical techniques to identify the species from which they were derived and to separate a suitable sample for dating by accelerator mass spectrometry. Although these techniques need much further development and detailed testing, the ages obtained in this first study were consistent with other data, indicating that the concept is viable. For the first time, the time of use of stone tools has been found directly, rather than by stratigraphic or other archaeologic inferential techniques.
Little is known about the influence of meal timing and energy consumption patterns throughout the day on glucose regulation during pregnancy. We examined the association of maternal feeding patterns with glycaemic levels among lean and overweight pregnant women. In a prospective cohort study in Singapore, maternal 24-h dietary recalls, fasting glucose (FG) and 2-h postprandial glucose (2HPPG) concentrations were measured at 26–28 weeks of gestation. Women (n 985) were classified into lean (BMI<23 kg/m2) or overweight (BMI≥23 kg/m2) groups. They were further categorised as predominantly daytime (pDT) or predominantly night-time (pNT) feeders according to consumption of greater proportion of energy content from 07.00 to 18.59 hours or from 19.00 to 06.59 hours, respectively. On stratification by weight status, lean pNT feeders were found to have higher FG than lean pDT feeders (4·36 (sd 0·38) v. 4·22 (sd 0·35) mmol/l; P=0·002); however, such differences were not observed between overweight pDT and pNT feeders (4·49 (sd 0·60) v. 4·46 (sd 0·45) mmol/l; P=0·717). Using multiple linear regression with confounder adjustment, pNT feeding was associated with higher FG in the lean group (β=0·16 mmol/l; 95 % CI 0·05, 0·26; P=0·003) but not in the overweight group (β=0·02 mmol/l; 95 % CI −0·17, 0·20; P=0·879). No significant association was found between maternal feeding pattern and 2HPPG in both the lean and the overweight groups. In conclusion, pNT feeding was associated with higher FG concentration in lean but not in overweight pregnant women, suggesting that there may be an adiposity-dependent effect of maternal feeding patterns on glucose tolerance during pregnancy.
A low temperature amorphous zinc indium oxide (ZIO) thin film transistor (TFT) backplane technology for high information content flexible organic light emitting diode (OLED) displays has been developed. We have fabricated 4.1-in. diagonal OLED backplanes on the Flexible Display Center’s six-inch wafer-scale pilot line using ZIO as the active layer. The ZIO based TFTs exhibited an effective saturation mobility of 18.6 cm2/V-s and a threshold voltage shift of 2.2 Volts or less under positive and negative gate bias DC stress for 10000 seconds. We report on the critical steps in the evolution of the backplane process: the qualification of the low temperature (200°C) ZIO process, the stability of the devices under forward and reverse bias stress, the transfer of the process to flexible plastic substrates, and the fabrication of white organic light emitting diode (OLED) displays.
In the casual political rhetoric about environmental regulation, it is often claimed that the U.S. government regulates on the basis of risk while the European Union (or EU member states) regulates on the basis of hazard. The implication is that the U.S. government relies on a more rigorous, scientific process of assessment than does the EU, which allegedly helps explain why the EU is more pro-regulation than is the United States.
An alternative view, advanced originally by the late Professor Aaron Wildavsky of the University of California-Berkeley and amplified in a recent book by Professor Jonathan Wiener of Duke University, and colleagues, is that societies engage in a process of “risk selection.” What worries some societies does not worry others.
Multiple interaction computer simulations have been used to determine the properties of collision cascades in liquid In targets induced by normally incident 5 keV Ar+ ions. Below the first atomic layer the cascade becomes Thompson-like relatively quickly. However, within the first atomic layer the angular distribution of moving atoms became forward peaked by 150 fs and remained so until,∼300 fs. Energy and angle resolved (EARN) spectra were calculated for the ejected atoms. The peak of the energy distribution shifted to lower energies at larger ejection angles, and the angular distributions became broader for lower energy particles. Both results agree with recent experimental data, and with a simple model proposed bg Garrison. Our results suggest that the detailed structure of the surface layer is very important in the sputtering process.
The preparation and purification of macroscopic quantities of buckminsterfullerenes  or buckyballs has ignited an explosion of research into their physical and chemical properties, and a variety of strategies for preparing new fullerene-based materials. Free radical synthesis is an appealing approach for forming polymeric fullerene materials. We report a polymeric fullerene material prepared by reacting pure C60 with xylylene from the thermolysis of paracyclophane. Addition of xylylene to a purple solution of C60 in toluene solution at -78 °C resulted in an olive-green solution from which an insoluble brown powder precipitated upon warming to room temperature. Analyses of the powder by solid state 13C MAS NMR, IR, and thermal gravimetric analysis are consistent with C60-xylylene copolymer.
Multilayered Ir oxide films were prepared on Ti and Pt:Ir electrodes by the thermal decomposition of successive layers of alcohol solutions of IrCl3. The charge capacity of the thermally-formed Ir oxide films (TIROF) and the reversibility of surface oxide-related reactions were evaluated in a physiological saline solution using potential sweep and current pulse techniques. The TIROF-coated electrodes had electrochemical properties similar to an Ir electrode coated with an anodically-formed oxide. The charge injection limits before gassing ranged from 5–10 mC/cm2 for TIROF-Ti and 1–3 mC/cm2 for TIROF-Pt:Ir with biphasic, charge-balanced current pulses of 0.2 ms duration. No Pt dissolution was detected during >100 hr stimulation with TIROF-Pt:Ir electrodes. Small amounts of Ir dissolution were detected which might result from passive leaching of residual chloride complexes of Ir. The TIROF coatings remained firmly attached to the substrate metal during long term pulsing and abrasion tests. The properties of TIROF coatings, e.g., high charge capacity for reversible charge injection and good abrasion and corrosion resistance, are of great advantage for neural prosthesis applications.
We have used 13C magic-angle spinning (MAS) nuclear magnetic resonance (NMR) to characterize the structure and rotational dynamics of C60 containing oxygen molecules located in the interstitial sites of the fcc lattice. Under normal conditions, a narrow peak at 143.7 ppm is observed for C60. When exposed to oxygen at moderate pressures, several additional resonances appear in the 13C MAS NMR spectrum. These secondary resonances are shifted downfield from the main peak at 143.7 ppm and are due to the Fermi-contact interaction of the paramagnetic oxygen molecules with the 13C nuclear spins. The presence of oxygen depresses the orientational ordering transition by ca. 20 K as observed by DSC. The spin-lattice relaxation time (T1) of each secondary peak shows a minimum near the ordering transition, indicating that this transition is not dependent on the number of oxygen molecules surrounding an individual C60 molecule. The T1 due to paramagnetic relaxation, normalized by the number of surrounding oxygen molecules, is constant. This observation demonstrates that within a given sample, the dynamics of C60 molecules are independent of the number of surrounding oxygen molecules.
A titanate Synroc ceramic for the immobilization of Pu-bearing waste was designed to consist of 70 wt% zirconolite (CaZrTi2O7) + 15 wt% nepheline (NaAlSiO4) + 15 wt% rutile (TiO2). It contained 10 wt% of Pu plus 6 wt% of Gd as a neutron poison. The material was made by our standard sol-gel route, using a mixture of alkoxides and nitrates, followed by stirdrying and calcination. It was fabricated by hot-pressing at 1150–1250°C/20 MPa for 2 hours in a collapsible metal bellows. Though zirconolite was the majority phase, ∼20 wt% of perovskite also formed. Some of the Na, intended for nepheline, partitioned into the titanate phases. 84-day differential total leach rates of Pu were in the order of 10−5 g/m2/d at 90 and 200°C. Companion ceramics using molar substitution of Ce for Pu confirmed the idea that Ce is a good simulant of Pu from a solid state chemical view, but that there are limitations in terms of leach rate parallels.
The spectral editing properties of the 29Si NMR INEPT heteronuclear transfer experiment have been utilized for the identification and characterization of hydrolysis and initial condensation products in methyltrimethoxysilane (MTMS) sol-gel materials. 29Si NMR assignments in MTMS are complicated by a small spectral dispersion (∼0.5 ppm) and two different 29Si-1H J couplings. By using analytical expressions for the INEPT signal response with multiple heteronuclear J couplings, unambiguous spectral assignments can be made. For this organomethoxysilane the rate of hydrolysis was found to be very rapid and significantly faster than either the water- or alcohol-producing condensation reactions. The hydrolysis species of both the MTMS monomer and its initial T1 condensation products follow statistical distributions that can be directly related to the extent of the hydrolysis reactions. The role of the statistical distribution of hydrolysis products on the production and synthetic control of organically modified sol-gels is discussed.
The retro Diels-Alder reaction was used to modify porosity in hydrocarbon-bridged polysilsesquioxane gels. Microporous polysilsesquioxanes incorporating a thermally labile Diels-Alder adduct as the hydrocarbon bridging group were prepared by sol-gel polymerization of trans-2, 3-bis(triethoxysilyl)norbornene. Upon heating the 2, 3-norbornenylene-bridged polymers at temperatures above 250°C, the norbornenylene-bridging group underwent a retro Diels-Alder reaction losing cyclopentadiene and leaving behind a ethenylene-bridged polysilsesquioxane. Less than theoretical quantities of cyclopentadiene were volatilized indicating that some of the diene was either reacting with the silanol and olefinic rich material or undergoing oligomerization. Both scanning electron microscopy and nitrogen sorption porosimetry revealed net coarsening of pores (and reduction of surface area) in the materials with thermolysis.
In-situ filling through hydrolysis and condensation of silicon alkoxides dissolved into polymers has been utilized to generate nanocomposites in which the filler phase can be intimately associated with the polymer on relatively small length scales. One problem of the method has been achieving useful fill volumes without bulk phase separation of the growing inorganic component from the polymer. In this paper, we describe the preparation of a new class of nanocomposite materials in which the inorganic filler phase is pre-assembled before copolymerization with an organic monomer. Maleimide monomers, prepared from alkoxysilylpropyl amines and maleic anhydride, were protected against side reactions by forming the oxonorbornene Diels-Alder adduct with furan. The monomers were then reacted under solgel conditions to form oligomers or polymers making up the filler phase. The material was activated by thermal deprotection of the maleimide and reacted with organic monomers or polymers to form the filled nanocomposite.
Drug attrition during discovery and development continues to be a major hurdle for drug approval. Even as the number of investigational new drug (IND) filings increased between 1986 and 2006, new drug applications (NDA) remained flat during the same time period due to attrition. The major reason for drug attrition in the clinic is preclinical toxicity, accounting for 35 percent of terminated drugs, followed closely by clinical efficacy and clinical safety. Attrition due to preclinical toxicity is even higher (~70 percent) when compounds that fail prior to candidate drug nomination are considered. Toxicologists need to learn from the success of approaches employed in drug metabolism and pharmacokinetics (DMPK) where attrition due to unfavorable PK has been reduced from a high of 40 percent in 1991 to only 6 percent in 2001. This success was achieved by applying a variety of in vivo and in vitro approaches including predictive in silico and in vitro assays prior to preclinical and clinical administration.
The traditional toxicologist manages nominated candidate drugs through the rigors of clinical development; however, in the rising need to reduce drug attrition, there is a paradigm shift in training toxicologists to evaluate the safety of pharmacological targets or new chemical entities (NCEs) through all phases of drug discovery and development. However, toxicologists are faced with a tougher hurdle in reducing attrition than groups in drug metabolism and pharmacokinetics.
The dissolution in de-ionized water (DIW) at 90 and 150 °C of Cs and Ba from mechanically polished Cs-doped Ba hollandite samples is essentially congruent. The normalized Ba and Cs release rates were <0.001 g/m2/day after 56 days in DIW at 90 °C, and the Ba normalized release rate of a Cs-free sample was 0.01 g/m2/day after 56 days in DIW at 150 °C. Varying the pH between approximately 2.5 and 12.9 affected only the Ba dissolution rates of hollandite by half an order of magnitude. The dissolution rates of all species decrease with increasing leaching time due to the formation of partly impervious surface coatings of Al- and Ti-rich species. These surface coatings were investigated by scanning electron microscopy, and in some cases by cross-sectional transmission electron microscopy and x-ray photoelectron spectroscopy.
From the Barbies and Batmobiles of the primary school to the cuddly pups and bulldozers of the preschool, an impressive amount of pretend play happens with objects designed to be used in pretense. On one day, the rage is for Cabbage Patch dolls and Ninja Turtles and on another Beanie Babies and Nano fighters. Some modern toys are promotional and come with an adult-authored story line. Others represent generic characters (babies or pets) or real creatures from field, zoo, or farm.
Representational toys have been found in archeological digs, pyramids, and ancient graves (King, 1979). They have found their way into museums recording the development of playthings throughout the ages. Dolls were once made of corn husks or banyan leaves; toy canoes were scooped from fallen tree limbs; horses and tigers were fashioned from mud or carved from stone. Human culture has endowed these representational objects with immense significance as though these artifacts of childhood hold clues to the beginnings of human thinking, expression, and feeling. As early as the second year of life children spontaneously talk to and for these inanimate representations of real or imagined creatures; children make these objects act upon things and with one another. From an early age, human children gleefully attribute life, feeling, and thinking to inanimate things.