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Compound-specific radiocarbon (14C) dating often requires working with small samples of < 100 µg carbon (µgC). This makes the radiocarbon dates of biomarker compounds very sensitive to biases caused by extraneous carbon of unknown composition, a procedural blank, which is introduced to the samples during the steps necessary to prepare a sample for radiocarbon analysis by accelerator mass spectrometry (i.e., isolating single compounds from a heterogeneous mixture, combustion, gas purification and graphitization). Reporting accurate radiocarbon dates thus requires a correction for the procedural blank. We present our approach to assess the fraction modern carbon (F14C) and the mass of the procedural blanks introduced during the preparation procedures of lipid biomarkers (i.e. n-alkanoic acids) and lignin phenols. We isolated differently sized aliquots (6–151 µgC) of n-alkanoic acids and lignin phenols obtained from standard materials with known F14C values. Each compound class was extracted from two standard materials (one fossil, one modern) and purified using the same procedures as for natural samples of unknown F14C. There is an inverse linear relationship between the measured F14C values of the processed aliquots and their mass, which suggests constant contamination during processing of individual samples. We use Bayesian methods to fit linear regression lines between F14C and 1/mass for the fossil and modern standards. The intersection points of these lines are used to infer F14Cblank and mblank and their associated uncertainties. We estimate 4.88 ± 0.69 μgC of procedural blank with F14C of 0.714 ± 0.077 for n-alkanoic acids, and 0.90 ± 0.23 μgC of procedural blank with F14C of 0.813 ± 0.155 for lignin phenols. These F14Cblank and mblank can be used to correct AMS results of lipid and lignin samples by isotopic mass balance. This method may serve as a standardized procedure for blank assessment in small-scale radiocarbon analysis.
Cognitive impairment is a core feature of major depressive disorder (MDD). Cognitive remediation may improve cognition in MDD, yet so far, the underlying neural mechanisms are unclear. This study investigated changes in intrinsic neural activity in MDD after a cognitive remediation trial.
In a longitudinal design, 20 patients with MDD and pronounced cognitive deficits and 18 healthy controls (HC) were examined using resting-state functional magnetic resonance imaging. MDD patients received structured cognitive remediation therapy (CRT) over 5 weeks. The whole-brain fractional amplitude of low-frequency fluctuations was computed before the first and after the last training session. Univariate methods were used to address regionally-specific effects, and a multivariate data analysis strategy was employed to investigate functional network strength (FNS).
MDD patients significantly improved in cognitive function after CRT. Baseline comparisons revealed increased right caudate activity and reduced activity in the left frontal cortex, parietal lobule, insula, and precuneus in MDD compared to HC. In patients, reduced FNS was found in a bilateral prefrontal system at baseline (p < 0.05, uncorrected). In MDD, intrinsic neural activity increased in right inferior frontal gyrus after CRT (p < 0.05, small volume corrected). Left inferior parietal lobule, left insula, left precuneus, and right caudate activity showed associations with cognitive improvement (p < 0.05, uncorrected). Prefrontal network strength increased in patients after CRT, but this increase was not associated with improved cognitive performance.
Our findings support the role of intrinsic neural activity of the prefrontal cortex as a possible mediator of cognitive improvement following CRT in MDD.
We present the second data release (DR2) of the SkyMapper Southern Survey, a hemispheric survey carried out with the SkyMapper Telescope at Siding Spring Observatory in Australia, using six optical filters: u, v, g, r, i, z. DR2 is the first release to go beyond the
) limit of the Shallow Survey released in the first data release (DR1), and includes portions of the sky at full survey depth that reach
mag in g and r filters. The DR2 photometry has a precision as measured by internal reproducibility of 1% in u and v, and 0.7% in griz. More than 21 000
have data in some filters (at either Shallow or Main Survey depth) and over 7 000
have deep Main Survey coverage in all six filters. Finally, about 18 000
have Main Survey data in i and z filters, albeit not yet at full depth. The release contains over 120 000 images, as well as catalogues with over 500 million unique astrophysical objects and nearly 5 billion individual detections. It also contains cross-matches with a range of external catalogues such as Gaia DR2, Pan-STARRS1 DR1, GALEX GUVcat, 2MASS, and AllWISE, as well as spectroscopic surveys such as 2MRS, GALAH, 6dFGS, and 2dFLenS.
We present a numerical methodology for construction of reduced-order models (ROMs) of fluid flows through the combination of flow modal decomposition and regression analysis. Spectral proper orthogonal decomposition is applied to reduce the dimensionality of the model and, at the same time, filter the proper orthogonal decomposition temporal modes. The regression step is performed by a deep feedforward neural network (DNN), and the current framework is implemented in a context similar to the sparse identification of nonlinear dynamics algorithm. A discussion on the optimization of the DNN hyperparameters is provided for obtaining the best ROMs and an assessment of these models is presented for a canonical nonlinear oscillator and the compressible flow past a cylinder. Then the method is tested on the reconstruction of a turbulent flow computed by a large eddy simulation of a plunging airfoil under dynamic stall. The reduced-order model is able to capture the dynamics of the leading edge stall vortex and the subsequent trailing edge vortex. For the cases analysed, the numerical framework allows the prediction of the flow field beyond the training window using larger time increments than those employed by the full-order model. We also demonstrate the robustness of the current ROMs constructed via DNNs through a comparison with sparse regression. The DNN approach is able to learn transient features of the flow and presents more accurate and stable long-term predictions compared to sparse regression.
Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.
Type 310S stainless steel was exposed in air at 900°C and simultaneously examined periodically by X-ray diffraction in an attempt to determine the structural evolution of the compounds formed on its surface. The adherent oxide product was found to be a two-layered scale composed of an inner sesquioxide and an outer spinel layer. Both of these compounds exhibited systematic changes in their unit cell sizes as a function of increasing exposure time at constant temperature. The spinel showed an increase in its lattice parameter while the sesquioxide and stainless steel substrate both had decreases in their parameters proportional to the square root of exposure time. In each of the three phases, the rate of change was constant up to approximately four hours after which the parameters approached a limiting value. Evidence also exists for the presence of at least localized stresses in the scales.
Posttraumatic stress disorder (PTSD) and stress/trauma exposure are cross-sectionally associated with advanced DNA methylation age relative to chronological age. However, longitudinal inquiry and examination of associations between advanced DNA methylation age and a broader range of psychiatric disorders is lacking. The aim of this study was to examine if PTSD, depression, generalized anxiety, and alcohol-use disorders predicted acceleration of DNA methylation age over time (i.e. an increasing pace, or rate of advancement, of the epigenetic clock).
Genome-wide DNA methylation and a comprehensive set of psychiatric symptoms and diagnoses were assessed in 179 Iraq/Afghanistan war veterans who completed two assessments over the course of approximately 2 years. Two DNA methylation age indices (Horvath and Hannum), each a weighted index of an array of genome-wide DNA methylation probes, were quantified. The pace of the epigenetic clock was operationalized as change in DNA methylation age as a function of time between assessments.
Analyses revealed that alcohol-use disorders (p = 0.001) and PTSD avoidance and numbing symptoms (p = 0.02) at Time 1 were associated with an increasing pace of the epigenetic clock over time, per the Horvath (but not the Hannum) index of cellular aging.
This is the first study to suggest that posttraumatic psychopathology is longitudinally associated with a quickened pace of the epigenetic clock. Results raise the possibility that accelerated cellular aging is a common biological consequence of stress-related psychopathology, which carries implications for identifying mechanisms of stress-related cellular aging and developing interventions to slow its pace.
OBJECTIVES/SPECIFIC AIMS: The purpose of the present secondary data analysis was to examine the effect of moderate-severe disturbed sleep before the start of radiation therapy (RT) on subsequent RT-induced pain. METHODS/STUDY POPULATION: Analyses were performed on 676 RT-naïve breast cancer patients (mean age 58, 100% female) scheduled to receive RT from a previously completed nationwide, multicenter, phase II randomized controlled trial examining the efficacy of oral curcumin on radiation dermatitis severity. The trial was conducted at 21 community oncology practices throughout the US affiliated with the University of Rochester Cancer Center NCI’s Community Oncology Research Program (URCC NCORP) Research Base. Sleep disturbance was assessed using a single item question from the modified MD Anderson Symptom Inventory (SI) on a 0–10 scale, with higher scores indicating greater sleep disturbance. Total subjective pain as well as the subdomains of pain (sensory, affective, and perceived) were assessed by the short-form McGill Pain Questionnaire. Pain at treatment site (pain-Tx) was also assessed using a single item question from the SI. These assessments were included for pre-RT (baseline) and post-RT. For the present analyses, patients were dichotomized into 2 groups: those who had moderate-severe disturbed sleep at baseline (score≥4 on the SI; n=101) Versus those who had mild or no disturbed sleep (control group; score=0–3 on the SI; n=575). RESULTS/ANTICIPATED RESULTS: Prior to the start of RT, breast cancer patients with moderate-severe disturbed sleep at baseline were younger, less likely to have had lumpectomy or partial mastectomy while more likely to have had total mastectomy and chemotherapy, more likely to be on sleep, anti-anxiety/depression, and prescription pain medications, and more likely to suffer from depression or anxiety disorder than the control group (all p’s≤0.02). Spearman rank correlations showed that changes in sleep disturbance from baseline to post-RT were significantly correlated with concurrent changes in total pain (r=0.38; p<0.001), sensory pain (r=0.35; p<0.001), affective pain (r=0.21; p<0.001), perceived pain intensity (r=0.37; p<0.001), and pain-Tx (r=0.35; p<0.001). In total, 92% of patients with moderate-severe disturbed sleep at baseline reported post-RT total pain compared with 79% of patients in the control group (p=0.006). Generalized linear estimating equations, after controlling for baseline pain and other covariates (baseline fatigue and distress, age, sleep medications, anti-anxiety/depression medications, prescription pain medications, and depression or anxiety disorder), showed that patients with moderate-severe disturbed sleep at baseline had significantly higher mean values of post-RT total pain (by 39%; p=0.033), post-RT sensory pain (by 41%; p=0.046), and post-RT affective pain (by 55%; p=0.035) than the control group. Perceived pain intensity (p=0.066) and pain-Tx (p=0.086) at post-RT were not significantly different between the 2 groups. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that moderate-severe disturbed sleep prior to RT is an important predictor for worsening of pain at post-RT in breast cancer patients. There could be several plausible reasons for this. Sleep disturbance, such as sleep loss and sleep continuity disturbance, could result in impaired sleep related recovery and repair of tissue damage associated with cancer and its treatment; thus, resulting in the amplification of pain. Sleep disturbance may also reduce pain tolerance threshold through increased sensitization of the central nervous system. In addition, pain and sleep disturbance may share common neuroimmunological pathways. Sleep disturbance may modulate inflammation, which in turn may contribute to increased pain. Further research is needed to confirm these findings and whether interventions targeting sleep disturbance in early phase could be potential alternate approaches to reduce pain after RT.
Background: Minimally invasive techniques for graft procurement are the norm in cardiac surgery and yet their use in neurosurgery is only in its infancy. We present the case of a 10-year-old boy presenting with fluctuating right facial and upper extremity weakness who was found to have a giant, partially thrombosed, fusiform aneurysm of the M1 segment of the left MCA. Methods: Endoscopic harvesting of the saphenous vein was performed with a procedure time of 30 minutes. The graft was used as an interposition graft between the common carotid artery and the superior M2 division of the MCA, which was tunneled subcutaneously. Once Doppler ultrasound confirmed good flow through the graft, an aneurysm clip was then secured on the M1, proximal to the saccular component of the fusiform aneurysm and just distal to the anterior temporal branch. Results: Intraoperative 2D and 3D angiogram confirmed a patent extracranial to intracranial bypass with thrombosis of the giant fusiform M1 aneurysm. By 1-month post-operatively, he had returned to school and routine activities. He continues to do well 6 months post-operatively with a minimal and well-healed donor site scar. Conclusions: Endoscopic graft harvesting is an emerging option in the pediatric population undergoing extracranial to intracranial bypass, associated with lower wound complications and improved cosmesis.
We present the first data release of the SkyMapper Southern Survey, a hemispheric survey carried out with the SkyMapper Telescope at Siding Spring Observatory in Australia. Here, we present the survey strategy, data processing, catalogue construction, and database schema. The first data release dataset includes over 66 000 images from the Shallow Survey component, covering an area of 17 200 deg2 in all six SkyMapper passbands uvgriz, while the full area covered by any passband exceeds 20 000 deg2. The catalogues contain over 285 million unique astrophysical objects, complete to roughly 18 mag in all bands. We compare our griz point-source photometry with Pan-STARRS1 first data release and note an RMS scatter of 2%. The internal reproducibility of SkyMapper photometry is on the order of 1%. Astrometric precision is better than 0.2 arcsec based on comparison with Gaia first data release. We describe the end-user database, through which data are presented to the world community, and provide some illustrative science queries.
From a 45ks Chandra observation of V42G Oph we have obtained high-resolution X-ray spectra at moderate signal-to-noise, and a, good quality, uninterrupted lightcurve. The spectra are reasonably fit with a cooling flow model, similar to EX Hya and U Gem. Our analysis of the Chandra and additional X-ray/optical lightcurves reveals a persistent modulation at 4.2 hr from 1988 to 2003, likely the white dwarf spin period indicating an intermediate polar nature for V426 Oph.
In 2015, the American College of Obstetricians and Gynecologists issued a recommendation to screen women for depression and anxiety symptoms at least once during the perinatal period. Nevertheless, many identified women will not receive care from a behavioral health specialist. Listening Visits (LV), developed for delivery by nurses and validated in the United Kingdom, have recently been evaluated in a US-based randomized controlled trial (RCT) which recruited research participants from three home-visiting programs and an urban OB/GYN practice. RCT results indicated clinically and significant improvement in depression symptoms. To bridge the gap between evidence and practice, and based on experiences garnered at the OB/GYN site during the RCT, this development paper proposes a strategy for implementing depression screening and LV into routine clinical care in this practice setting.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
A QTL (TM-QTL) identified on ovine chromosome 18 (Walling et al., 2004), which increases loin muscle depth by 4-8% in UK Texel sheep, is of interest for the sheep industry as a potential means to increase carcass value. Since the contribution of Texel genes to the UK slaughter generation is generally through use of Texel sires to produce crossbred slaughter lambs (e.g. Texel x Mule lambs), it is necessary to verify the effects of the TM-QTL on loin muscularity and other carcass traits in such crossbred progeny of Texel sires before explotiation of the TM-QTL in commercial sheep populations.
The SkyMapper Transient survey (SMT) is exploring variability in the southern sky by performing (a) a rolling search to discover and study supernovæ, and (b) a Target of Opportunity programme that uses the robotic SkyMapper Telescope at Siding Spring Observatory. The supernova survey is obtaining a non-targeted sample of Type Ia supernovæ (SNe Ia) at low redshifts, z < 0.1, and studying other interesting transients found with the search strategy. We have a Target of Opportunity programme with an automatic response mechanism to search for optical counterparts to gravitational-wave and fast radio-burst events; it benefits from SkyMapper’s large field of view of 5.7 sq. deg. and a rapid data reduction pipeline.
We present first results of the SMT survey. The SMT pipeline can process and obtain potential candidates within 12 hours of observation. It disentangles real transients from processing artefacts using a machine-learning algorithm. To date, SMT has discovered over 60 spectroscopically confirmed supernovæ, several peculiar objects, and over 40 SNe Ia including one (SNIa 2016hhd) which was found within the first few days of explosion. We have also participated in searches for optical counterparts of gravitational waves, fast radio bursts and other transients, and have published observations of the optical counterpart of the gravitational-wave event GW170817. We also participate in coordinated observations with the Deeper Wider Faster programme, and the Kepler K2 cosmology project.
The Taipan galaxy survey (hereafter simply ‘Taipan’) is a multi-object spectroscopic survey starting in 2017 that will cover 2π steradians over the southern sky (δ ≲ 10°, |b| ≳ 10°), and obtain optical spectra for about two million galaxies out to z < 0.4. Taipan will use the newly refurbished 1.2-m UK Schmidt Telescope at Siding Spring Observatory with the new TAIPAN instrument, which includes an innovative ‘Starbugs’ positioning system capable of rapidly and simultaneously deploying up to 150 spectroscopic fibres (and up to 300 with a proposed upgrade) over the 6° diameter focal plane, and a purpose-built spectrograph operating in the range from 370 to 870 nm with resolving power R ≳ 2000. The main scientific goals of Taipan are (i) to measure the distance scale of the Universe (primarily governed by the local expansion rate, H0) to 1% precision, and the growth rate of structure to 5%; (ii) to make the most extensive map yet constructed of the total mass distribution and motions in the local Universe, using peculiar velocities based on improved Fundamental Plane distances, which will enable sensitive tests of gravitational physics; and (iii) to deliver a legacy sample of low-redshift galaxies as a unique laboratory for studying galaxy evolution as a function of dark matter halo and stellar mass and environment. The final survey, which will be completed within 5 yrs, will consist of a complete magnitude-limited sample (i ⩽ 17) of about 1.2 × 106 galaxies supplemented by an extension to higher redshifts and fainter magnitudes (i ⩽ 18.1) of a luminous red galaxy sample of about 0.8 × 106 galaxies. Observations and data processing will be carried out remotely and in a fully automated way, using a purpose-built automated ‘virtual observer’ software and an automated data reduction pipeline. The Taipan survey is deliberately designed to maximise its legacy value by complementing and enhancing current and planned surveys of the southern sky at wavelengths from the optical to the radio; it will become the primary redshift and optical spectroscopic reference catalogue for the local extragalactic Universe in the southern sky for the coming decade.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
Data from the in-school sample of the PROSPER preventive intervention dissemination trial were used to investigate associations between alcohol dehydrogenase genes and alcohol use across adolescence, and whether substance misuse interventions in the 6th and 7th grades (targeting parenting, family functioning, social norms, youth decision making, and peer group affiliations) modified associations between these genes and adolescent use. Primary analyses were run on a sample of 1,885 individuals and included three steps. First, we estimated unconditional growth curve models with separate slopes for alcohol use from 6th to 9th grade and from 9th to 12th grade, as well as the intercept at Grade 9. Second, we used intervention condition and three alcohol dehydrogenase genes, 1B (ADH1B), 1C (ADH1C), and 4 (ADH4) to predict variance in slopes and intercept. Third, we examined whether genetic influences on model slopes and intercepts were moderated by intervention condition. The results indicated that the increase in alcohol use was greater in early adolescence than in middle adolescence; two of the genes, ADH1B and ADH1C, significantly predicted early adolescent slope and Grade 9 intercept, and associations between ADH1C and both early adolescent slope and intercept were significantly different across control and intervention conditions.