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Objective: To investigate the effects of methylphenidate on long-term executive and neuropsychological functioning in children with attention problems following TBI, as well as the relationship between methylphenidate associated changes in lab-based neuropsychological measures of attentional control, processing speed, and executive functioning and parent- or self-report measures of everyday executive functioning. Method: 26 children aged 6–17 years, who were hospitalized for moderate-to-severe blunt head trauma 6 or more months previously, were recruited from a large children’s hospital medical center. Participants were randomized into a double-masked, placebo-controlled cross-over clinical trial. Participants completed a comprehensive neuropsychological battery and parent- and self-report ratings of everyday executive functioning at baseline, and at 4 weeks and 8 weeks following upward titration of medication to an optimal dose or while administered a placebo. Results: Methylphenidate was associated with significant improvements in processing speed, sustained attention, and both lab-based and everyday executive functioning. Significant treatment-by-period interactions were found on a task of sustained attention. Participants who were randomized to the methylphenidate condition for the first treatment period demonstrated random or erratic responding, with slower and more variable response times when given placebo during the second period. Conclusion: Results indicate that methylphenidate treatment is associated with positive outcomes in processing speed, sustained attention, and both lab-based and everyday measures of executive functioning compared to placebo group. Additionally, results suggest sustained attention worsens when discontinuing medication. (JINS, 2019, 25, 740–749)
BACKGROUND: IGTS is a rare phenomenon of paradoxical germ cell tumor (GCT) growth during or following treatment despite normalization of tumor markers. We sought to evaluate the frequency, clinical characteristics and outcome of IGTS in patients in 21 North-American and Australian institutions. METHODS: Patients with IGTS diagnosed from 2000-2017 were retrospectively evaluated. RESULTS: Out of 739 GCT diagnoses, IGTS was identified in 33 patients (4.5%). IGTS occurred in 9/191 (4.7%) mixed-malignant GCTs, 4/22 (18.2%) immature teratomas (ITs), 3/472 (0.6%) germinomas/germinomas with mature teratoma, and in 17 secreting non-biopsied tumours. Median age at GCT diagnosis was 10.9 years (range 1.8-19.4). Male gender (84%) and pineal location (88%) predominated. Of 27 patients with elevated markers, median serum AFP and Beta-HCG were 70 ng/mL (range 9.2-932) and 44 IU/L (range 4.2-493), respectively. IGTS occurred at a median time of 2 months (range 0.5-32) from diagnosis, during chemotherapy in 85%, radiation in 3%, and after treatment completion in 12%. Surgical resection was attempted in all, leading to gross total resection in 76%. Most patients (79%) resumed GCT chemotherapy/radiation after surgery. At a median follow-up of 5.3 years (range 0.3-12), all but 2 patients are alive (1 succumbed to progressive disease, 1 to malignant transformation of GCT). CONCLUSION: IGTS occurred in less than 5% of patients with GCT and most commonly after initiation of chemotherapy. IGTS was more common in patients with IT-only on biopsy than with mixed-malignant GCT. Surgical resection is a principal treatment modality. Survival outcomes for patients who developed IGTS are favourable.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
The effect of tunnel cations on tunnel size in α-MnO2 structured (hollandite, cryptomelane) materials has long been of interest, as the tunnel size effects catalytic and transport properties. Previous research on the tunnel size has focused on potassium cryptomelane (KxMn8O16). This paper uses synthetic control of silver content in AgxMn8O16 to investigate the effect that tunnel silver occupancy has on the lattice parameters. Materials with silver (x) content between 1.14 and 1.66 were synthesized, synchrotron diffraction and Rietveld Refinement was used to determine lattice parameters. The lattice parameters were found to contract as silver content increases (from 9.774 Å to 9.738 Å), in contrast to previous investigations of other tunnel cations.
Highly detailed structural characterization is required to understand the discharge mechanism in order to effectively investigate α-MnO2 structured lithium battery cathode materials. This paper discusses recent findings which elucidate the lithiation mechanism of silver-hollandite, AgxMn8O16. For Ag1.2Mn8O16, the structure is not significantly perturbed during the first 2 equivalents of lithiation and the electrochemistry is highly reversible. Upon 4 equivalents of lithiation, the structure becomes highly distorted, in correlation with capacity fade observed over 40 cycles. Notably, regarding capacity fade, modifications to Ag/Mn ratio are less impactful than modifications to the α-MnO2 crystallite size. This is shown in comparisons of two materials with the same stoichiometry (Ag1.4Mn8O16) and differing crystallite size (10 and 15 nm).
In cattle early gastrulation-stage embryos (Stage 5), four tissues can be discerned: (i) the top layer of the embryonic disc consisting of embryonic ectoderm (EmE); (ii) the bottom layer of the disc consisting of mesoderm, endoderm and visceral hypoblast (MEH); (iii) the trophoblast (TB); and (iv) the parietal hypoblast. We performed microsurgery followed by RNA-seq to analyse the transcriptome of these four tissues as well as a developmentally earlier pre-gastrulation embryonic disc. The cattle EmE transcriptome was similar at Stages 4 and 5, characterised by the OCT4/SOX2/NANOG pluripotency network. Expression of genes associated with primordial germ cells suggest their presence in the EmE tissue at these stages. Anterior visceral hypoblast genes were transcribed in the Stage 4 disc, but no longer by Stage 5. The Stage 5 MEH layer was equally similar to mouse embryonic and extraembryonic visceral endoderm. Our data suggest that the first mesoderm to invaginate in cattle embryos is fated to become extraembryonic. TGFβ, FGF, VEGF, PDGFA, IGF2, IHH and WNT signals and receptors were expressed, however the representative members of the FGF families differed from that seen in equivalent tissues of mouse embryos. The TB transcriptome was unique and differed significantly from that of mice. FGF signalling in the TB may be autocrine with both FGFR2 and FGF2 expressed. Our data revealed a range of potential inter-tissue interactions, highlighted significant differences in early development between mice and cattle and yielded insight into the developmental events occurring at the start of gastrulation.
We present low-frequency spectral energy distributions of 60 known radio pulsars observed with the Murchison Widefield Array telescope. We searched the GaLactic and Extragalactic All-sky Murchison Widefield Array survey images for 200-MHz continuum radio emission at the position of all pulsars in the Australia Telescope National Facility (ATNF) pulsar catalogue. For the 60 confirmed detections, we have measured flux densities in 20 × 8 MHz bands between 72 and 231 MHz. We compare our results to existing measurements and show that the Murchison Widefield Array flux densities are in good agreement.
Because polarization encodes geometrical information about unresolved scattering regions, it provides a unique tool for analyzing the 3-D structures of supernovae (SNe) and their surroundings. SNe of all types exhibit time-dependent spectropolarimetric signatures produced primarily by electron scattering. These signatures reveal physical phenomena such as complex velocity structures, changing illumination patterns, and asymmetric morphologies within the ejecta and surrounding material. Interpreting changes in polarization over time yields unprecedentedly detailed information about supernovae, their progenitors, and their evolution.
Begun in 2012, the SNSPOL Project continues to amass the largest database of time-dependent spectropolarimetric data on SNe. I present an overview of the project and its recent results. In the future, combining such data with interpretive radiative transfer models will further constrain explosion mechanisms and processes that shape SN ejecta, uncover new relationships among SN types, and probe the properties of progenitor winds and circumstellar material.
Fontan survivors have depressed cardiac index that worsens over time. Serum biomarker measurement is minimally invasive, rapid, widely available, and may be useful for serial monitoring. The purpose of this study was to identify biomarkers that correlate with lower cardiac index in Fontan patients.
Methods and results
This study was a multi-centre case series assessing the correlations between biomarkers and cardiac magnetic resonance-derived cardiac index in Fontan patients ⩾6 years of age with biochemical and haematopoietic biomarkers obtained ±12 months from cardiac magnetic resonance. Medical history and biomarker values were obtained by chart review. Spearman’s Rank correlation assessed associations between biomarker z-scores and cardiac index. Biomarkers with significant correlations had receiver operating characteristic curves and area under the curve estimated. In total, 97 cardiac magnetic resonances in 87 patients met inclusion criteria: median age at cardiac magnetic resonance was 15 (6–33) years. Significant correlations were found between cardiac index and total alkaline phosphatase (−0.26, p=0.04), estimated creatinine clearance (0.26, p=0.02), and mean corpuscular volume (−0.32, p<0.01). Area under the curve for the three individual biomarkers was 0.63–0.69. Area under the curve for the three-biomarker panel was 0.75. Comparison of cardiac index above and below the receiver operating characteristic curve-identified cut-off points revealed significant differences for each biomarker (p<0.01) and for the composite panel [median cardiac index for higher-risk group=2.17 L/minute/m2 versus lower-risk group=2.96 L/minute/m2, (p<0.01)].
Higher total alkaline phosphatase and mean corpuscular volume as well as lower estimated creatinine clearance identify Fontan patients with lower cardiac index. Using biomarkers to monitor haemodynamics and organ-specific effects warrants prospective investigation.
Levels of pollution, including contamination by toxic metals, in the Thames estuary reduced over the last four decades of the 20th century. This 2014 study investigates whether the declines in the bioavailabilities of trace metals (Ag, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, V, Zn) have continued in the 21st century, using a suite of littoral biomonitors also employed in 2001 – the brown seaweed Fucus vesiculosus, the strandline, talitrid amphipod Orchestia gammarellus and the estuarine barnacle Amphibalanus improvisus. Bioaccumulated concentrations represent relative measures of the total bioavailabilities of each metal to the biomonitor over a previous time period, and can be compared over space and over time. Trace metal bioavailabilities varied along the estuary, and, in general, fell between 2001 and 2014, a reflection of the continuing remediation of the Thames estuary from its severely polluted state in the middle of the 20th century.
To describe current Ebola treatment center (ETC) locations, their capacity to care for Ebola virus disease patients, and infection control infrastructure features.
A 19-question survey was distributed electronically in April 2015. Responses were collected via email by June 2015 and analyzed in an electronic spreadsheet.
The survey was sent to and completed by site representatives of each ETC.
The survey was sent to all 55 ETCs; 47 (85%) responded.
Of the 47 responding ETCs, there are 84 isolation beds available for adults and 91 for children; of these pediatric beds, 35 (38%) are in children’s hospitals. In total, the simultaneous capacity of the 47 reporting ETCs is 121 beds. On the basis of the current US census, there are 0.38 beds per million population. Most ETCs have negative pressure isolation rooms, anterooms, and a process for category A waste sterilization, although only 11 facilities (23%) have the capability to sterilize infectious waste on site.
Facilities developed ETCs on the basis of Centers for Disease Control and Prevention guidance, but specific capabilities are not mandated at this present time. Owing to the complex and costly nature of Ebola virus disease treatment and variability in capabilities from facility to facility, in conjunction with the lack of regulations, nationwide capacity in specialized facilities is limited. Further assessments should determine whether ETCs can adapt to safely manage other highly infectious disease threats.
Infect. Control Hosp. Epidemiol. 2016;37(3):313–318
FFQ are commonly used to examine the association between diet and disease. They are the most practical method for usual dietary data collection as they are relatively inexpensive and easy to administer. In Australia, the Cancer Council of Victoria FFQ (CCVFFQ) version 2 and the online Commonwealth Scientific and Industrial Research Organisation FFQ (CSIROFFQ) are used. The aim of our study was to establish the level of agreement between nutrient intakes captured using the online CSIROFFQ and the paper-based CCVFFQ. The CCVFFQ and the online CSIROFFQ were completed by 136 healthy participants. FFQ responses were analysed to give g per d intake of a range of nutrients. Agreement between twenty-six nutrient intakes common to both FFQ was measured by a variety of methods. Nutrient intake levels that were significantly correlated between the two FFQ were carbohydrates, total fat, Na and MUFA. When assessing ranking of nutrients into quintiles, on average, 56 % of the participants (for all nutrients) were classified into the same or adjacent quintiles in both FFQ, with the highest percentage agreement for sugar. On average, 21 % of participants were grossly misclassified by three or four quintiles, with the highest percentage misclassification for fibre and Fe. Quintile agreement was similar to that reported by other studies, and we concluded that both FFQ are suitable tools for dividing participants’ nutrient intake levels into high- and low-consumption groups. Use of either FFQ was not appropriate for obtaining accurate estimates of absolute nutrient intakes.
We present the observed “continuum” levels of polarization as a function of time for four well-observed Type II-Plateau supernovae (SNe II-P; Fig. 1), the class of SNe decisively determined to arise from red supergiant stars (Smartt 2009). All four objects show temporally increasing degrees of polarization through the end of the photospheric phase, with some exhibiting early-time polarization that challenge existing models (e.g., Dessart and Hillier 2011) to reproduce. A fundamental ejecta asymmetry is present in this photometrically diverse sample of type II SNe, and it probably takes different forms (e.g., 56Ni blobs/fingers, large scale deformation). We acknowledge support from NSF grants AST-1009571 and AST-1210311.
The Murchison Widefield Array is a new low-frequency interferometric radio telescope built in Western Australia at one of the locations of the future Square Kilometre Array. We describe the automated radio-frequency interference detection strategy implemented for the Murchison Widefield Array, which is based on the aoflagger platform, and present 72–231 MHz radio-frequency interference statistics from 10 observing nights. Radio-frequency interference detection removes 1.1% of the data. Radio-frequency interference from digital TV is observed 3% of the time due to occasional ionospheric or atmospheric propagation. After radio-frequency interference detection and excision, almost all data can be calibrated and imaged without further radio-frequency interference mitigation efforts, including observations within the FM and digital TV bands. The results are compared to a previously published Low-Frequency Array radio-frequency interference survey. The remote location of the Murchison Widefield Array results in a substantially cleaner radio-frequency interference environment compared to Low-Frequency Array’s radio environment, but adequate detection of radio-frequency interference is still required before data can be analysed. We include specific recommendations designed to make the Square Kilometre Array more robust to radio-frequency interference, including: the availability of sufficient computing power for radio-frequency interference detection; accounting for radio-frequency interference in the receiver design; a smooth band-pass response; and the capability of radio-frequency interference detection at high time and frequency resolution (second and kHz-scale respectively).
The current study sought to examine the utility of intra-individual variability (IIV) in distinguishing participants with prodromal Huntington disease (HD) from nongene-expanded controls. IIV across 15 neuropsychological tasks and within-task IIV using a self-paced timing task were compared as a single measure of processing speed (Symbol Digit Modalities Test [SDMT]) in 693 gene-expanded and 191 nongene-expanded participants from the PREDICT-HD study. After adjusting for depressive symptoms and motor functioning, individuals estimated to be closest to HD diagnosis displayed higher levels of across- and within-task variability when compared to controls and those prodromal HD participants far from disease onset (FICV(3,877)=11.25; p<.0001; FPacedTiming(3,877)=22.89; p<.0001). When prodromal HD participants closest to HD diagnosis were compared to controls, Cohen’s d effect sizes were larger in magnitude for the within-task variability measure, paced timing (−1.01), and the SDMT (−0.79) and paced tapping coefficient of variation (CV) (−0.79) compared to the measures of across-task variability [CV (0.55); intra-individual standard deviation (0.26)]. Across-task variability may be a sensitive marker of cognitive decline in individuals with prodromal HD approaching disease onset. However, individual neuropsychological tasks, including a measure of within-task variability, produced larger effect sizes than an index of across-task IIV in this sample. (JINS, 2015, 21, 8–21)
We present an analysis of the parsec-scale jet structure of the quasar 4C+21.35 with a resolution of 0.1 milliarcseconds based on 63 epochs of Very Long Baseline Array observations at 43 GHz from 2007 June to 2014 May along with the Fermi LAT γ-ray light curve and multi-frequency optical photometric and polarimetric data. We find that the innermost jet of the quasar consists of a very compact core of size ~0.03 mas, as well as feature A1 located 0.16 ± 0.03 mas from the core. The distance of A1 remains fairly stable, but its position angle with respect to the core changes from -10 to +10 deg. We detect 4 superluminal knots in the inner jet with apparent speeds ranging from 10c to 20c. The first two components appeared in the jet during the high γ-ray state of the quasar from mid-2010 to early 2011, while the fourth knot appears to be connected with the γ-ray active state in late 2013 - early 2014. The first knot can be associated with the dramatic VHE flare in 2010 June and possesses an extreme Doppler factor ~60. We find that maxima in the γ-ray light curve coincide with epochs of interaction between the moving knots and the core and feature A1. This suggests that the core and A1 are recollimation shocks where γ-ray flares occur. The Chandra 0.5-6 keV image reveals the existence of X-ray emission in the kiloparsec scale jet of the quasar that can be explained via inverse Compton scattering off the cosmic microwave background by relativistic electrons if no deceleration occurs between the parsec- and kiloparsec-scale jets.