Introducing BITTSy: The Behavioral Infant & Toddler Testing System.

This manuscript introduces BITTSy, the Behavioral Infant & Toddler Testing System. This software system is capable of running the headturn preference procedure, preferential looking, conditioned headturn, and visual fixation/habituation procedures. It uses only commercial-off-theshelf (COTS) hardware to implement the procedures in an affordable and space-efficient setup. The software package, example protocols and data sets, and manual are freely available and downloadable from go.umd.edu/BITTSy, making this entire set of procedures available to resource-limited labs. Researchers can easily use BITTSy at multiple sites in a uniform manner, resulting in a standardized, powerful research tool that can enhance cross-site research collaborations.

Enabling near-atomic-scale analysis of frozen water.

Transmission electron microscopy went through a revolution enabling routine cryo-imaging of biological and (bio)chemical systems, in liquid form. Yet, these approaches typically lack advanced analytical capabilities. Here, we used atom probe tomography to analyze frozen liquids in three dimensions with subnanometer resolution. We introduce a specimen preparation strategy using nanoporous gold. We report data on 2- to 3-µm-thick layers of ice formed from both high-purity deuterated water and a solution of 50 mM NaCl in high-purity deuterated water. The analysis of the gold-ice interface reveals a substantial increase in the solute concentrations across the interface. We explore a range of experimental parameters to show that atom probe analyses of bulk aqueous specimens come with their own challenges and discuss physical processes that produce the observed phenomena. Our study demonstrates the viability of using frozen water as a carrier for near-atomic-scale analysis of objects in solution by atom probe tomography.

Design, construction and characterisation of a portable gamma-ray spectrometer for low-level natural occurring radioactive material ex-situ measurement.

The activity concentrations in naturally occurring radioactive material (NORM) samples are conventionally measured using a gamma-ray spectrometer with a single detector (mostly HPGe or NaI:Tl) enclosed in a lead shield. In this work, a passive water shield to reduce background radiation reaching the detectors was designed using GEANT4-toolkit Monte Carlo simulations and then constructed. This measurement system is portable and cost-effective for ex-situ measurements. IAEA-375 soil and beach sand each placed in Marinelli beakers were measured using two LaBr3:Ce detectors in singles and coin-cidence modes. A novel method of background reduction by using photon time-of-flight was employed together with the measurement of the two photons energies. These samples were also measured in singles mode using a NaI:Tl detector inside the constructed water shield and HPGe detector shielded with lead to compare and validate the results of LaBr3:Ce detectors measurement. Both the simulated and measured results show that the water shield (500 mm thick) attenuates 2614.5 keV gamma rays by 90 %. The minimum detectable activity (MDA) measured for 24 h using the NaI:Tl detector without shield and inside the water shield are; 546 Bq kg-1 and 146 Bq kg-1 at 1460.8 keV (40K), 194 Bq kg-1 and 15 Bq kg-1 at 1764.5 keV (238U series), and 131 Bq kg-1 and 15 Bq kg-1 at 911.2 keV (232Th series), respectively. The measured activity concentrations of 238U and 232Th series and 40K radionuclides inside IAEA-375 soil agree with certified values to within measurement uncertainties. The measured activity of 138La in the LaBr3:Ce detector crystal is 263.8 ± 26.8 Bq kg-1. The internal activity of the LaBr3:Ce detector increases the MDA at 1460.8 keV and 2614.5 keV, which limits the measurement of primordial radionuclides with low activity concentration in singles mode. The activity concentrations of 238U and 232Th series radionuclides in beach sand were measured using NaI:Tl and LaBr3:Ce detectors. The results are consistent with those from HPGe measurement to within uncertainties.

Determination of activity concentration of 238U and 232Th series radionuclides in soil using a gamma-ray spectrometer in singles and coincidence modes.

Traditionally, activity concentrations of naturally occurring radioactive materials (NORMs) are measured using a gamma-ray spectrometer with a single detector shielded with lead. In this measurement, a gamma-ray spectrometer comprising an array of four LaBr3:Ce detectors without shielding was used. This spectrometer allowed for measurement in singles and coincidence (gamma-gamma) modes. In addition to using the coincidence method, a novel method of background reduction by using the photon time-of-flight was utilized. Activity concentration of 238U and 232Th series radionuclides in soil reference (IAEA-375) and beach-sand (Bs) were measured in singles and coincidence modes. In coincidence mode, the minimum detectable activities (MDAs) were lower by a factor of 8-36 than for singles mode. Activity concentration of 238U and 232Th series in soil material (IAEA-375) were determined in coincidence mode while it was below MDA in singles mode. The results correlate with the certified values to within the uncertainty although the uncertainties were high because of low statistics.

Radon in groundwater baseline study prior to unconventional shale gas development and hydraulic fracturing in the Karoo Basin (South Africa).

The prospect of unconventional shale gas development in the semi-arid Karoo Basin (South Africa) has created the prerequisite to temporally characterise the natural radioactivity in associated groundwater which is solely depended on for drinking and agriculture purposes. Radon (222Rn) was the primary natural radionuclide of interest in this study; however, supplementary radium (226Ra and 228Ra) in-water measurements were also conducted. A total of 53 aquifers spanning three provinces were studied during three separate measurement campaigns from 2014 to 2016. The Karoo Basin's natural radon-in-water levels can be characterised by a minimum of 1 ±â€¯1 Bq/L (consistent with zero or below LLD), a maximum of 183 ±â€¯18 Bq/L and mean of 41 ±â€¯5 Bq/L. The mean radon-in-water levels for shallow aquifers were systematically higher (55 ±â€¯10 Bq/L) compared to deep (14 ±â€¯3 Bq/L) or mixed aquifers (20 ±â€¯6 Bq/L). Radon-in-water activity concentration fluctuations were predominantly observed from shallow aquifers compared to the generally steady levels of deep aquifers. A collective seasonal mean radon-in-water levels increase from the winter of 2014 (44 ±â€¯8 Bq/L) to winter of 2016 (61 ±â€¯16 Bq/L) was noticed which could be related to the extreme national drought experienced in 2015. Radium-in-water (228Ra and 226Ra) levels ranged from below detection level to a maximum of 0.008 Bq/L (226Ra) and 0.015 Bq/L (228Ra). The 228Ra/226Ra ratio was characterised by a minimum of 0.93, a maximum of 6.5 and a mean value of 3.3 ±â€¯1.3. Developing and improving baseline naturally occurring radionuclide groundwater databases is vital to study potential radiological environmental impacts attributed to industrial processes such as hydraulic fracturing or mining.

Estimating gestational age at birth from fundal height and additional anthropometrics: a prospective cohort study.

OBJECTIVE: Accurate assessment of gestational age (GA) is critical to paediatric care, but is limited in developing countries without access to ultrasound. Our objectives were to assess the accuracy of prediction of GA at birth and preterm birth classification using routinely collected anthropometry measures. DESIGN: Prospective cohort study. SETTING: United States. POPULATION OR SAMPLE: A total of 2334 non-obese and 468 obese pregnant women. METHODS: Enrolment GA was determined based on last menstrual period, confirmed by first-trimester ultrasound. Maternal anthropometry and fundal height (FH) were measured by a standardised protocol at study visits; FH alone was additionally abstracted from medical charts. Neonatal anthropometry measurements were obtained at birth. To estimate GA at delivery, we developed three predictor models using longitudinal FH alone and with maternal and neonatal anthropometry. For all predictors, we repeatedly sampled observations to construct training (60%) and test (40%) sets. Linear mixed models incorporated longitudinal maternal anthropometry and a shared parameter model incorporated neonatal anthropometry. We assessed models' accuracy under varied scenarios. MAIN OUTCOME MEASURES: Estimated GA at delivery. RESULTS: Prediction error for various combinations of anthropometric measures ranged between 13.9 and 14.9 days. Longitudinal FH alone predicted GA within 14.9 days with relatively stable prediction errors across individual race/ethnicities [whites (13.9 days), blacks (15.1 days), Hispanics (15.5 days) and Asians (13.1 days)], and correctly identified 75% of preterm births. The model was robust to additional scenarios. CONCLUSIONS: In low-risk, non-obese women, longitudinal FH measures alone can provide a reasonably accurate assessment of GA when ultrasound measures are not available. TWEETABLE ABSTRACT: Longitudinal fundal height alone predicts gestational age at birth when ultrasound measures are unavailable.

Nanoscale mechanism of the stabilization of nanoporous gold by alloyed platinum.

Nanoporous gold (NPG) is usually made by electrochemical dealloying of Ag from binary AgAu alloys. The resulting nanoscale ligaments are not very stable, and tend to coarsen with time by surface self-diffusion, especially in electrolyte, which may lead to inferior electrocatalytic properties. Addition of a small amount of Pt to the precursor alloy is known to refine and stabilize the nanoporous product (NPG-Pt). However, the mechanisms by which Pt serves to refine the microstructure remain poorly understood. The present study aims to expand our knowledge of the role of Pt by examining NPG-Pt at atomic resolution with Atom Probe Tomography (APT), as well as by aberration-corrected Transmission Electron Microscopy. Atomic level observation of Pt enrichment on ligament surfaces sheds light on the underlying mechanisms that give rise to Pt's refining effect. Owing to improved Ag retention with higher Pt content, NPG-Pt1 (made by dealloying Ag77Au22Pt1) was shown to have the highest surface area-to-volume ratio, compared to NPG-Pt3 (made by dealloying Ag77Au20Pt3). Quantitative estimates reveal up to 5-fold enrichment of Pt at nanoligament surfaces, compared to the precursor content, in NPG-Pt. The interface between the dealloyed layer and the substrate was captured by APT, for the first time. The findings of this investigation add insight into the functionality of NPG-Pt and its prospective catalytic performance.

A splice site variant in the SUV39H2 gene in Greyhounds with nasal parakeratosis.

Hereditary nasal parakeratosis (HNPK), described in the Labrador Retriever breed, is a monogenic autosomal recessive disorder that causes crusts and fissures on the nasal planum of otherwise healthy dogs. Our group previously showed that this genodermatosis may be caused by a missense variant located in the SUV39H2 gene encoding a histone 3 lysine 9 methyltransferase, a chromatin modifying enzyme with a potential role in keratinocyte differentiation. In the present study, we investigated a litter of Greyhounds in which six out of eight puppies were affected with parakeratotic lesions restricted to the nasal planum. Clinically and histologically, the lesions were comparable to HNPK in Labrador Retrievers. Whole genome sequencing of one affected Greyhound revealed a 4-bp deletion at the 5'-end of intron 4 of the SUV39H2 gene that was absent in 188 control dog and three wolf genomes. The variant was predicted to disrupt the 5'-splice site with subsequent loss of SUV39H2 function. The six affected puppies were homozygous for the variant, whereas the two non-affected littermates were heterozygous. Genotyping of a larger cohort of Greyhounds revealed that the variant is segregating in the breed and that this breed might benefit from genetic testing to avoid carrier × carrier matings.

Is the timed loaded standing test a valid measure of back muscle endurance in people with vertebral osteoporosis?

Timed loaded standing (TLS) is a suggested measure of back muscle endurance for people with vertebral osteoporosis. Surface electromyography revealed back muscles work harder and fatigue during TLS. The test end-point and total time were associated with back fatigue. The findings help demonstrate the concurrent validity of the TLS test. INTRODUCTION: The TLS test is suggested as a measure of back muscle endurance for patients with vertebral osteoporosis. However, to date, no study has demonstrated that TLS does measure back extensor or erector spinae (ES) muscle endurance. We used surface electromyography (sEMG) to investigate the performance of the thoracic ES muscles during TLS. METHODS: Thirty-six people with vertebral osteoporosis with a mean age of 71.6 (range 45-86) years participated. sEMG recordings were made of the ES at T3 and T12 bilaterally during quiet standing (QS) and TLS. The relative (%) change in sEMG amplitude between conditions was compared. Fatigue was evaluated by analysing the change in median frequency (MF) of the sEMG signal during TLS, and the correlation between maximal TLS time and rate of MF decline was examined. RESULTS: Activity in the ES increased significantly during TLS at all electrode locations. During TLS, the MF declined at a mean rate of -24.2% per minute (95% C.I. -26.5 to -21.9%). The MF slope and test time were strongly correlated (r2 = 0.71), and at test end, the final MF dropped to an average 89% (95% C.I. 85 to 93%) of initial MF. Twenty-eight participants (78%) reported fatigue was the main reason for stopping, and for eight (22%), it was pain. CONCLUSIONS: This study demonstrates that TLS challenges the ES muscles in the thoracic region and results in ES fatigue. Endurance time and the point at which the TLS test ends are strongly related to ES fatigue.

The Development of Technology for Effective Respiratory-Gated Irradiation Using an Image-Guided Small Animal Irradiator.

The development of image-guided small animal irradiators represents a significant improvement over standard irradiators by enabling preclinical studies to mimic radiotherapy in humans. The ability to deliver tightly collimated targeted beams, in conjunction with gantry or animal couch rotation, has the potential to maximize tumor dose while sparing normal tissues. However, the current commercial platforms do not incorporate respiratory gating, which is required for accurate and precise targeting in organs subject to respiration related motions that may be up to the order of 5 mm in mice. Therefore, a new treatment head assembly for the Xstrahl Small Animal Radiation Research Platform (SARRP) has been designed. This includes a fast X-ray shutter subsystem, a motorized beam hardening filter assembly, an integrated transmission ionization chamber to monitor beam delivery, a kinematically positioned removable beam collimator and a targeting laser exiting the center of the beam collimator. The X-ray shutter not only minimizes timing errors but also allows beam gating during imaging and treatment, with irradiation only taking place during the breathing cycle when tissue movement is minimal. The breathing related movement is monitored by measuring, using a synchronous detector/lock-in amplifier that processes diffuse reflectance light from a modulated light source. After thresholding of the resulting signal, delays are added around the inhalation/exhalation phases, enabling the "no movement" period to be isolated and to open the X-ray shutter. Irradiation can either be performed for a predetermined time of X-ray exposure, or through integration of a current from the transmission monitor ionization chamber (corrected locally for air density variations). The ability to successfully deliver respiratory-gated X-ray irradiations has been demonstrated by comparing movies obtained using planar X-ray imaging with and without respiratory gating, in addition to comparing dose profiles observed from a collimated beam on EBT3 radiochromic film mounted on the animal's chest. Altogether, the development of respiratory-gated irradiation facilitates improved dose delivery during animal movement and constitutes an important new tool for preclinical radiation studies. This approach is particularly well suited for irradiation of orthotopic tumors or other targets within the chest and abdomen where breathing related movement is significant.

Radon and Thoron In-air Occupational Exposure Study within Selected Wine Cellars of the Western Cape (South Africa) and Associated Annual Effective Doses.

This is the first known study of exposure of Rn (radon) and secondarily Rn (thoron) in-air activity concentrations assessed within nine selected wine cellars in four wine districts of the Western Cape (South Africa) and the associated annual occupational effective doses. E-PERM electret ion chambers (EIC) and RAD-7 α-detectors were used to perform these measurements. The radon in-air levels ranged from 12 ± 4 Bq m to 770 ± 40 Bq m within the nine selected wine cellars. Eight of the nine wine cellars (excluding results from cellar w-6) had a median radon in-air activity concentration of 48 ± 8 Bq m. Continuous thoron in-air activity concentration levels were also measured near an internal granite wall of the wine cellar w-6 (barrel room), where peak levels of up to 1,520 ± 190 Bq m and an average of 680 ± 30 Bq m were observed. The occupational annual effective dose due to radon and decay progeny exposure in-air within the selected wine cellars ranged from 0.08 ± 0.03 mSv to 4.9 ± 0.3 mSv with a median of 0.32 ± 0.04 mSv (Tmax = 2,000 h). The annual effective dose within the wine cellar (w-6) ranged up to a maximum of 2.5 ± 0.4 mSv (Tmax = 2000 h) due to exposure to thoron and decay progeny. In general, most of the wines cellars pose negligible associated health risk to personnel due to ionizing radiation exposure from the inhalation of radon and progeny. Under certain conditions (proximity and exposure time), caution should be exercised at wine cellar w-6 because of elevated thoron in-air levels.

Self-assembly of a space-tessellating structure in the binary system of hard tetrahedra and octahedra.

We report the formation of a binary crystal of hard polyhedra due solely to entropic forces. Although the alternating arrangement of octahedra and tetrahedra is a known space-tessellation, it had not previously been observed in self-assembly simulations. Both known one-component phases - the dodecagonal quasicrystal of tetrahedra and the densest-packing of octahedra in the Minkowski lattice - are found to coexist with the binary phase. Apart from an alternative, monoclinic packing of octahedra, no additional crystalline phases were observed.

Radon Levels Measured at a Touristic Thermal Spa Resort in Montagu (South Africa) and Associated Effective Doses.

Radon activity concentrations (in water and in air) were measured at 13 selected locations at the Avalon Springs thermal spa resort in Montagu (Western Cape, South Africa) to estimate the associated effective dose received by employees and visitors. A RAD-7 detector (DURRIDGE), based on alpha spectrometry, and electret detectors (E-PERM®Radelec) were used for these radon measurements. The primary source of radon was natural thermal waters from the hot spring, which were pumped to various locations on the resort, and consequently a range of radon in-water analyses were performed. Radon in-water activity concentration as a function of time (short term and long term measurements) and spatial distributions (different bathing pools, etc.) were studied. The mean radon in-water activity concentrations were found to be 205 ± 6 Bq L (source), 112 ± 5 Bq L (outdoor pool) and 79 ± 4 Bq L (indoor pool). Radon in-air activity concentrations were found to range between 33 ± 4 Bq m (at the outside bar) to 523 ± 26 Bq m (building enclosing the hot spring's source). The most significant potential radiation exposure identified is that due to inhalation of air rich in radon and its progeny by the resort employees. The annual occupational effective dose due to the inhalation of radon progeny ranges from 0.16 ± 0.01 mSv to 0.40 ± 0.02 mSv. For the water samples collected, the Ra in-water activity concentrations from samples collected were below the lower detection limit (~0.7 Bq L) of the γ-ray detector system used. No significant radiological health risk can be associated with radon and progeny from the hot spring at the Avalon Springs resort.

Correction: Self-assembly of a space-tessellating structure in the binary system of hard tetrahedra and octahedra.

Correction for 'Self-assembly of a space-tessellating structure in the binary system of hard tetrahedra and octahedra' by A. T. Cadotte et al., Soft Matter, 2016, DOI: .

RNA binding proteins as regulators of immune cell biology.

Sequence-specific RNA binding proteins (RBP) are important regulators of the immune response. RBP modulate gene expression by regulating splicing, polyadenylation, localization, translation and decay of target mRNAs. Increasing evidence suggests that RBP play critical roles in the development, activation and function of lymphocyte populations in the immune system. This review will discuss the post-transcriptional regulation of gene expression by RBP during lymphocyte development, with particular focus on the Tristetraprolin family of RBP.

Microdosimetry of the Auger electron emitting 123I radionuclide using Geant4-DNA simulations.

Microdosimetric calculations of the Auger electron emitter (123)I were done in liquid water spheres using the Geant4 toolkit. The electron emission spectrum of (123)I produced by Geant4 is presented. Energy deposition and corresponding S-values were calculated to investigate the influence of the sub-cellular localization of the Auger emitter. It was found that S-values calculated by the Geant4 toolkit are generally lower than the values calculated by other Monte Carlo codes for the (123)I radionuclide. The differences in the compared S-values are mainly due to the different particle emission spectra employed by the respective computational codes and emphasizes the influence of the spectra on dosimetry calculations.

First-in-human study of pbi-05204, an oleander-derived inhibitor of akt, fgf-2, nf-κΒ and p70s6k, in patients with advanced solid tumors.

BACKGROUND: PBI-05204, a Nerium oleander extract (NOE) containing the cardiac glycoside oleandrin, inhibits the α-3 subunit of Na-K ATPase, as well as FGF-2 export, Akt and p70S6K, hence attenuating mTOR activity. This first-in-human study determined the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of PBI-05204 in patients with advanced cancer. Methods Forty-six patients received PBI-05204 by mouth for 21 of 28 days (3 + 3 trial design). Dose was escalated 100% using an accelerated titration design until grade 2 toxicity was observed. Plasma PK and mTOR effector (p70S6K and pS6) protein expressions were evaluated. Results Dose-limiting toxicities (grade 3 proteinuria, fatigue) were observed at dose level 8 (0.3383 mg/kg/day). Common possible drug-related adverse were fatigue (26 patients, 56.5%), nausea (19 patients, 41.3%) and diarrhea (15 patients, 32.6 %). Electrocardiogram monitoring revealed grade 1 atrioventricular block (N = 10 patients) and grade 2 supraventricular tachycardia (N = 1). The MTD was DL7 (0.2255 mg/kg) where no toxicity of grade ≥ 3 was observed in seven patients treated. Seven patients (15%) had stable disease > 4 months. Mean peak oleandrin concentrations up to 2 ng/mL were achieved, with area under the curves 6.6 to 25.5 µg/L*hr and a half-life range of 5-13 h. There was an average 10% and 35% reduction in the phosphorylation of Akt and pS6 in PBMC samples in 36 and 32 patients, respectively, tested between predose and 21 days of treatment. Conclusions PBI-05204 was well tolerated in heavily pretreated patients with advanced solid tumors. The recommended Phase II dose is 0.2255 mg/kg/day.

Analytical electron microscopy of a crack tip extracted from a stressed Alloy 800 sample exposed to an acid sulfate environment.

Alloy 800 (Fe-21Cr-33Ni) has been found susceptible to cracking in acid sulfate environments, but the mechanism is not well understood. Alloy 800 C-ring samples were exposed to an acid sulfate environment at 315°C and cracks were found with depths in excess of 300µm after 60h. Preparation of a TEM sample containing crack tips is challenging, but the ability to perform high-resolution microscopy at the crack tip would lend insight to the mechanism of acid sulfate stress corrosion cracking (AcSCC). The lift-out technique combined with a focused ion beam sample preparation was used to extract a crack tip along the cross-section of an acid sulfate crack in an Alloy 800 C-ring. TEM elemental analysis was done using EDS and EELS which identified a duplex oxide within the crack; an inner oxide consisting of a thin 3-4nm Cr-rich oxide and an outer oxide enriched in Fe and Cr. Preliminary conclusions and hypotheses resulted with respect to the mechanism of AcSCC in Alloy 800.