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Consumption of sugar sweetened beverages (SSBs) in infants and young children are less explored in Asian populations. The Growing in Singapore Towards healthy Outcomes (GUSTO) cohort study examined associations between SSB intakes at ages 18 months and 5 years with adiposity measures at age 6 years. We studied Singaporean infants/children with SSB intake assessed by food frequency questionnaires (FFQ) at ages 18 months (n=555) and 5 years (n=767). The median (interquartile range) for SSB intakes is 28(5.5-98) ml at age 18 months and 111 (57-198) ml at age 5 years. Associations between SSB intakes (100 ml/day increments and tertile categories) and adiposity measures (BMI standard deviation scores (s.d. unit), sum of skinfolds (SSFs)) and overweight/obesity status were examined using multivariable linear and Poisson regression models, respectively. After adjusting for confounders and additionally for energy intake, SSB intakes at age 18 months were not significantly associated with later adiposity measures and overweight/obesity outcomes. In contrast, at age 5 years, SSB intakes when modelled as 100ml/day increments were associated with higher BMI by 0.09 (95% CI: 0.02, 0.16) s.d. unit, higher SSF thickness by 0.68 (0.06, 1.44) mm, and increased risk for overweight/obesity by 1.2 times (1.07, 1.23) at age 6 years. Trends were consistent with SSB intakes modelled as categorical tertiles. In summary, SSB intake in young childhood is associated with higher risks of adiposity and risk for overweight/obesity. Public health policies working to reduce SSB consumption need to focus on prevention programs targeted at young children.
Space Infrared Telescope for Cosmology and Astrophysics (SPICA), the cryogenic infrared space telescope recently pre-selected for a ‘Phase A’ concept study as one of the three remaining candidates for European Space Agency (ESA's) fifth medium class (M5) mission, is foreseen to include a far-infrared polarimetric imager [SPICA-POL, now called B-fields with BOlometers and Polarizers (B-BOP)], which would offer a unique opportunity to resolve major issues in our understanding of the nearby, cold magnetised Universe. This paper presents an overview of the main science drivers for B-BOP, including high dynamic range polarimetric imaging of the cold interstellar medium (ISM) in both our Milky Way and nearby galaxies. Thanks to a cooled telescope, B-BOP will deliver wide-field 100–350
m images of linearly polarised dust emission in Stokes Q and U with a resolution, signal-to-noise ratio, and both intensity and spatial dynamic ranges comparable to those achieved by Herschel images of the cold ISM in total intensity (Stokes I). The B-BOP 200
m images will also have a factor
30 higher resolution than Planck polarisation data. This will make B-BOP a unique tool for characterising the statistical properties of the magnetised ISM and probing the role of magnetic fields in the formation and evolution of the interstellar web of dusty molecular filaments giving birth to most stars in our Galaxy. B-BOP will also be a powerful instrument for studying the magnetism of nearby galaxies and testing Galactic dynamo models, constraining the physics of dust grain alignment, informing the problem of the interaction of cosmic rays with molecular clouds, tracing magnetic fields in the inner layers of protoplanetary disks, and monitoring accretion bursts in embedded protostars.
There is a long history of exploitation of the South American river turtle Podocnemis expansa. Conservation efforts for this species started in the 1960s but best practices were not established, and population trends and the number of nesting females protected remained unknown. In 2014 we formed a working group to discuss conservation strategies and to compile population data across the species’ range. We analysed the spatial pattern of its abundance in relation to human and natural factors using multiple regression analyses. We found that > 85 conservation programmes are protecting 147,000 nesting females, primarily in Brazil. The top six sites harbour > 100,000 females and should be prioritized for conservation action. Abundance declines with latitude and we found no evidence of human pressure on current turtle abundance patterns. It is presently not possible to estimate the global population trend because the species is not monitored continuously across the Amazon basin. The number of females is increasing at some localities and decreasing at others. However, the current size of the protected population is well below the historical population size estimated from past levels of human consumption, which demonstrates the need for concerted global conservation action. The data and management recommendations compiled here provide the basis for a regional monitoring programme among South American countries.
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.
Background: Genetically-determined leukoencephalopathies comprise a rare group of inherited white matter disorders. The vast majority are associated with a progressive disease course and early death. This study seeks to determine the clinical and demographic correlates of stress in parents of leukodystrophy patients, for future clinical guidance. Methods: A cross-sectional study including 36 families was performed. Children aged 1 month to 12 years with a diagnosed leukodystrophy or genetically-determined leukoencephalopathy were included. 31 mothers and 24 fathers completed the Parental Stress Index, 4th edition (PSI-4). One demographic questionnaire was completed per family. Clinical data was gathered within 6 months of the questionnaires. Statistical analysis was performed with total stress (TS) scores as the primary outcome. Results: Mothers and fathers had comparable TS scores. No clinical or demographic factors predicted the father’s TS score. Greater ambulatory impairment, using the GMFCS scale, correlated to lower TS scores in the mother. Conclusions: The progressive nature of these conditions makes it such that anticipating a child’s inability to walk may cause more stress for mothers than a child’s actual inability to ambulate. The inability of all other variables to predict total stress highlights a need for individualized approaches when addressing stress in these families.
Background: 4H leukodystrophy is a genetic disorder typically characterized by hypomyelination, hypodontia and hypogonatotropic hypogonadism. Previously reported patients had considerable cognitive and motor deficits. We present a pair of siblings with a less severe phenotype. Methods: Patient data was obtained from medical records from the Children’s Hospital of Eastern Ontario. Results: The first patient was diagnosed with 4H leukodystrophy at the age of 21 years after genetic testing revealed a POLR3B mutation with a homozygous V523E variant. She has hypomyelination on MRI and a history of optic neuritis, as well as intermittent sensory and motor symptoms in the context of a diagnosis of multiple sclerosis. She has no clinical manifestations of 4H leukodystrophy. The patient is now 26 years old and has only mild neurological deficits. Her younger brother was diagnosed with 4H leukodystrophy at the age of 18 years and found to have the same genetic mutation as his sister. He has a history of seizures and mild learning disabilities. He is now 23 years old with no typical symptoms of 4H leukodystrophy. Conclusions: 4H leukodystrophy is usually associated with a severe, disabling phenotype and a poor prognosis. Our patients illustrate that a much milder phenotype exists.
After five positive randomized controlled trials showed benefit of mechanical thrombectomy in the management of acute ischemic stroke with emergent large-vessel occlusion, a multi-society meeting was organized during the 17th Congress of the World Federation of Interventional and Therapeutic Neuroradiology in October 2017 in Budapest, Hungary. This multi-society meeting was dedicated to establish standards of practice in acute ischemic stroke intervention aiming for a consensus on the minimum requirements for centers providing such treatment. In an ideal situation, all patients would be treated at a center offering a full spectrum of neuroendovascular care (a level 1 center). However, for geographical reasons, some patients are unable to reach such a center in a reasonable period of time. With this in mind, the group paid special attention to define recommendations on the prerequisites of organizing stroke centers providing medical thrombectomy for acute ischemic stroke, but not for other neurovascular diseases (level 2 centers). Finally, some centers will have a stroke unit and offer intravenous thrombolysis, but not any endovascular stroke therapy (level 3 centers). Together, these level 1, 2, and 3 centers form a complete stroke system of care. The multi-society group provides recommendations and a framework for the development of medical thrombectomy services worldwide.
Disturbances in emotion regulation (ER) are characteristic of both patients with bipolar disorder (BD) and schizophrenia (SZ). We investigated the temporal dynamics of brain activation during cognitive ER in BD and SZ to understand the contribution of temporal characteristics of disturbed ER to their unique and shared symptomatology.
Forty-six participants performed an ER-task (BD, n = 15; SZ, n = 16; controls, n = 15) during functional magnetic resonance imaging, in which they were instructed to use cognitive reappraisal techniques to regulate their emotional responses. Finite impulse response modeling was applied to estimate the temporal dynamics of brain responses during cognitive reappraisal (v. passive attending) of negative pictures. Group, time, and group × time effects were tested using multivariate modeling.
We observed a group × time interaction during ER in the ventrolateral prefrontal cortex (VLPFC), supplementary motor area (SMA) and inferior occipital gyrus. Patients with SZ demonstrated initial hyper-activation of the VLPFC and SMA activation that was not sustained in later regulatory phases. Response profiles in the inferior occipital gyrus in SZ showed abnormal activation in the later phases of regulation. BD-patients showed general blunted responsivity in these regions.
These results suggest that ER-disturbances in SZ are characterized by an inefficient initialization and failure to sustain regulatory control, whereas in BD, a failure to recruit regulatory resources may represent initial deficits in formulating adequate representations of the regulatory needs. This may help to further understand how ER-disturbances give rise to symptomatology of BD and SZ.
ALKS 3831, currently under development for the treatment of schizophrenia, is composed of olanzapine (OLZ) and a fixed dose of 10mg of samidorphan. In a Phase 2 study in stable patients with schizophrenia, ALKS 3831mitigated OLZ-associated weight gain while maintaining an antipsychotic efficacy profile similar to OLZ.
To assess the efficacy and safety of ALKS 3831 in patients with acute exacerbation of schizophrenia.
This was a Phase 3, 4-week, randomized, double-blind, active and placebo (PBO)-controlled study of ALKS 3831 in patients with acute exacerbation of schizophrenia (ClinicalTrials.gov: NCT02634346). Eligible patients (N=403) were randomized 1:1:1 to receive ALKS 3831, OLZ, or PBO. Patients were treated in an inpatient setting for the first 2weeks of the study and could be treated as inpatients or outpatients for the remaining 2weeks. Patients were excluded if they received OLZ within 6months prior to screening. Antipsychotic efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression–Severity (CGI-S) and CGI–Improvement (CGI-I) scales. Safety and tolerability were assessed as adverse events (AEs).
Of 401 randomized patients who received ALKS 3831, OLZ, or PBO, 91%, 89%, and 83% of patients, respectively, completed treatment. The most common reason for discontinuation was withdrawal by patient (6% in both the ALKS 3831and PBO groups, and 7% in the OLZ group). Baseline characteristics were generally similar between groups; however, baseline mean body mass index was higher in the OLZ group than in the ALKS 3831 group. Baseline mean±standard deviation scores were 101.7±11.9 for PANSS total score and 5.1±0.7 for CGI-S scale score. The mean OLZ dose was 18.4mg/day in both active treatment arms. Least squares (LS) mean difference±standard error (SE) vs PBO from baseline to Week 4 in PANSS total score was –6.4±1.8 (P<.001) for the ALKS 3831 group and –5.3±1.8 (P=.004) for the OLZ group. LS mean difference±SE vs PBO from baseline to Week 4 in CGI-S scale score was −0.4±0.1 (P=.002) for the ALKS3831 group and −0.4±0.1 (P<.001) for the OLZ group. The percentage of patients with improvement in PANSS response (≥30% from baseline) at Week 4 was 60%, 54%, and 38% in the ALKS 3831, OLZ, and PBO groups, respectively. The percentage of patients with an improvement in CGI-I scale response (score of ≤2) at Week 4 was 58%, 51%, and 33% in the ALKS 3831, OLZ, and PBO groups, respectively. Discontinuation due to AEs was low in all groups. Common AEs (≥5% in any group) included weight gain, somnolence, dry mouth, anxiety, headache, and schizophrenia.
Treatment with ALKS 3831 was more effective than PBO, as measured by the PANSS and CGI-S scale, and its antipsychotic efficacy was similar to the active control OLZ. The safety profile of ALKS 3831 was similar toOLZ.
Funding Acknowledgements: This study was funded by Alkermes, Inc.
Due to concerns over increasing fluoroquinolone (FQ) resistance among gram-negative organisms, our stewardship program implemented a preauthorization use policy. The goal of this study was to assess the relationship between hospital FQ use and antibiotic resistance.
Large academic medical center.
We performed a retrospective analysis of FQ susceptibility of hospital isolates for 5 common gram-negative bacteria: Acinetobacter spp., Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Primary endpoint was the change of FQ susceptibility. A Poisson regression model was used to calculate the rate of change between the preintervention period (1998–2005) and the postimplementation period (2006–2016).
Large rates of decline of FQ susceptibility began in 1998, particularly among P. aeruginosa, Acinetobacter spp., and E. cloacae. Our FQ restriction policy improved FQ use from 173 days of therapy (DOT) per 1,000 patient days to <60 DOT per 1,000 patient days. Fluoroquinolone susceptibility increased for Acinetobacter spp. (rate ratio [RR], 1.038; 95% confidence interval [CI], 1.005–1.072), E. cloacae (RR, 1.028; 95% CI, 1.013–1.044), and P. aeruginosa (RR, 1.013; 95% CI, 1.006–1.020). No significant change in susceptibility was detected for K. pneumoniae (RR, 1.002; 95% CI, 0.996–1.008), and the susceptibility for E. coli continued to decline, although the decline was not as steep (RR, 0.981; 95% CI, 0.975–0.987).
A stewardship-driven FQ restriction program stopped overall declining FQ susceptibility rates for all species except E. coli. For 3 species (ie, Acinetobacter spp, E. cloacae, and P. aeruginosa), susceptibility rates improved after implementation, and this improvement has been sustained over a 10-year period.
IR spectroscopy in the range 12–230 μm with the SPace IR telescope for Cosmology and Astrophysics (SPICA) will reveal the physical processes governing the formation and evolution of galaxies and black holes through cosmic time, bridging the gap between the James Webb Space Telescope and the upcoming Extremely Large Telescopes at shorter wavelengths and the Atacama Large Millimeter Array at longer wavelengths. The SPICA, with its 2.5-m telescope actively cooled to below 8 K, will obtain the first spectroscopic determination, in the mid-IR rest-frame, of both the star-formation rate and black hole accretion rate histories of galaxies, reaching lookback times of 12 Gyr, for large statistically significant samples. Densities, temperatures, radiation fields, and gas-phase metallicities will be measured in dust-obscured galaxies and active galactic nuclei, sampling a large range in mass and luminosity, from faint local dwarf galaxies to luminous quasars in the distant Universe. Active galactic nuclei and starburst feedback and feeding mechanisms in distant galaxies will be uncovered through detailed measurements of molecular and atomic line profiles. The SPICA’s large-area deep spectrophotometric surveys will provide mid-IR spectra and continuum fluxes for unbiased samples of tens of thousands of galaxies, out to redshifts of z ~ 6.
The physical processes driving the chemical evolution of galaxies in the last ~ 11Gyr cannot be understood without directly probing the dust-obscured phase of star-forming galaxies and active galactic nuclei. This phase, hidden to optical tracers, represents the bulk of the star formation and black hole accretion activity in galaxies at 1 < z < 3. Spectroscopic observations with a cryogenic infrared observatory like SPICA, will be sensitive enough to peer through the dust-obscured regions of galaxies and access the rest-frame mid- to far-infrared range in galaxies at high-z. This wavelength range contains a unique suite of spectral lines and dust features that serve as proxies for the abundances of heavy elements and the dust composition, providing tracers with a feeble response to both extinction and temperature. In this work, we investigate how SPICA observations could be exploited to understand key aspects in the chemical evolution of galaxies: the assembly of nearby galaxies based on the spatial distribution of heavy element abundances, the global content of metals in galaxies reaching the knee of the luminosity function up to z ~ 3, and the dust composition of galaxies at high-z. Possible synergies with facilities available in the late 2020s are also discussed.
To obtain more reliable information about the focal-depth distribution of icequakes, in April 1997 we operated an array of seven portable digital seismographs on Unteraargletscher, central Swiss Alps. Over 5000 events were detected by at least two instruments during the 9 day recording period. P-wave velocities (3770 m f) were determined from several calibration shots detonated at the glacier surface as well as in a 49 m deep borehole, whereas S-wave velocities (1860 ms–1) were derived from a simultaneous inversion for Vp/Vs6 applied to 169 icequakes. So far, hypocentral locations have been calculated for over 300 icequakes. Besides confirming the occurrence of shallow events associated with the opening of crevasses, our results show that a small but significant fraction of the hypocenters are located at or near the glacier bed. One event was found at an intermediate depth of about 120 m. Three-dimensional particle-motion diagrams of both explosions and icequakes clearly demonstrate that all vertical component seismograms from shallow sources are dominated by the Rayleigh wave. On the other hand, for events occurring at depths greater than about 40 m, the Rayleigh wave disappears almost entirely. Therefore, a qualitative analysis of the signal character provides direct information on the focal depth of an event and was used as an independent check of the locations obtained from traditional arrival-time inversions. Thus, our results demonstrate that deep icequakes do occur and that simple rheological models, according to which brittle deformation is restricted to the uppermost part of a glacier, may need revision.
OBJECTIVES/SPECIFIC AIMS: Recent evidence from resting-state fMRI studies have shown that brain network connectivity is altered in patients with neurodegenerative disorders. However, few studies have examined the complete connectivity patterns of these well-reported RSNs using a whole brain approach and how they compare between dementias. Here, we used advanced connectomic approaches to examine the connectivity of RSNs in Alzheimer disease (AD), Frontotemporal dementia (FTD), and age-matched control participants. METHODS/STUDY POPULATION: In total, 44 participants [27 controls (66.4±7.6 years), 13 AD (68.5.63±13.9 years), 4 FTD (59.575±12.2 years)] from an ongoing study at Indiana University School of Medicine were used. Resting-state fMRI data was processed using an in-house pipeline modeled after Power et al. (2014). Images were parcellated into 278 regions of interest (ROI) based on Shen et al. (2013). Connectivity between each ROI pair was described by Pearson correlation coefficient. Brain regions were grouped into 7 canonical RSNs as described by Yeo et al. (2015). Pearson correlation values were then averaged across pairs of ROIs in each network and averaged across individuals in each group. These values were used to determine relative expression of FC in each RSN (intranetwork) and create RSN profiles for each group. RESULTS/ANTICIPATED RESULTS: Our findings support previous literature which shows that limbic networks are disrupted in FTLD participants compared with AD and age-matched controls. In addition, interactions between different RSNs was also examined and a significant difference between controls and AD subjects was found between FP and DMN RSNs. Similarly, previous literature has reported a disruption between executive (frontoparietal) network and default mode network in AD compared with controls. DISCUSSION/SIGNIFICANCE OF IMPACT: Our approach allows us to create profiles that could help compare intranetwork FC in different neurodegenerative diseases. Future work with expanded samples will help us to draw more substantial conclusions regarding differences, if any, in the connectivity patterns between RSNs in various neurodegenerative diseases.
We present a simple model for the formation of elliptical galaxies, based on a binary clustering hierarchy of dark matter, the chemical enrichment of the gas at each level being controlled by supernovae. The initial conditions for the non-linear phases of galaxy formation are set by the post-recombination power spectrum of density fluctuations. We investigate two models for this power spectrum - the first is a straightforward power law, |δk|2 ∝ kn, and the second is Peeble's analytic approximation to the emergent spectrum in a universe dominated by cold dark matter. The normalisation is chosen such that on some scale, say M ∼ 1012M⊙, the objects that condense out have properties - radius and velocity dispersion - resembling ‘typical’ galaxies. There is some ambiguity in this due to the poorly determined mass-to-light ratio of a typical elliptical galaxy — we look at two normalisations, σ1D ∼ 350kms−1 and σ1D ∼ 140kms−1. The choice determines which of Compton cooling or hydrogen cooling is more important during the galaxy formation period. The non-linear behaviour of the perturbations is treated by the homogeneous sphere approximation.
The formation of disc galaxies is generally believed to involve the dissipative collapse of primordial gas clouds, moving in the potentials of dark, self-gravitating massive halos. Until now, most theories have considered only spherically symmetric collapse, with the luminous disc being formed out of a plane of cold gas which is in centrifugal equilibrium. However, it is unlikely that the halo potential will in fact be spherical.
A new method for the preparation of bone samples for δ18O-PO4 analysis has been developed. The phosphate from bone samples is separated and purified using ion exchange chromatography, and then precipitated as silver phosphate using the Firsching method. O2 is then extracted by reaction with bromine pentafluoride and converted to CO2 for isotopic analysis. Advantages of the silver phosphate technique over the bismuth phosphate technique are (1) the simplicity of the method, (2) silver phosphate is not hygroscopic so atmospheric water is not an oxygen contaminate, and (3) very small samples (2 mg to 10 mg) can be analyzed with an increase of precision compared to previous techniques. Iron and silica oxides added to Ag3PO4 standards produce no offset, which suggests that this new technique is not sensitive to interferences from cements commonly found in fossil bone material. Analyses have been performed on standards ranging in size from 30 mg to 2 mg with a σ1 of ± 0.05 per mil.
The δ18O-PO4 compositional pattern of the bones of modern vertebrates have been analyzed to provide a base for the interpretation of the δ18O-PO4 pattern of fossil vertebrates. The average %PO4 in modern mammals and reptiles is approximately 15% with a σ1 of 2-3 %. The average %PO4 of fossil reptiles range from 10 to 25% with σ1 variations of up to 10%. The %PO4 variation can be related to cementation of void spaces in the bone material. XRD analysis reveals that calcite, dolomite, ankerite, and silica cements are commonly present. FTIR (Fourier Transform Infrared Spectroscopy) yields low indices calculated according to the formula of Shemesh, 1990 [GCA 54(9):2433]. Thin sections of the fossil bone material show detailed structures. All this evidence suggests that the fossil bone δ18O-PO4 composition is pristine and not altered by diagenesis. The total δ18O-PO4 σ1 variation of 10 or more skeletal elements analyzed for each individual specimen varies from 0.1 per mil for a domestic cow (Bos) to 0.8 per mil for a Komodo dragon (Varanus). Variations in between appear to be related to thermal physiology and variations in drinking water δ18O due to seasonality or migration.
The thermal physiology of extinct reptiles has been a hotly debated topic for the last two decades, with no direct evidence available to help solve the debate. Oxygen isotopes are fractionated with respect to temperature between an animal's body water and bone phosphate, thus providing avenues for deriving the first direct evidence of dinosaur thermal physiology.
Multiple samples from both cortical and cancellous areas from individual bones were sampled in order to determine the heterogeneity of δ18O values within single bones. Bones from both the body core (ribs and vertebrae) and the extremities (limbs and caudal vertebrae) of known individual dinosaurs were sampled in this method. This allows for a comparison of isotopic heterogeneity from bones of all body regions. In ectothermic heterotherms or mass homeotherms the δ18O values from the extremities are expected to generally be heavier than those from ribs or dorsal vertebrae. It is also expected that there would be a greater degree of heterogeneity of δ18O values from bones in the extremities than those in the body core for these individuals. This relationship would result from the greater degree of heat loss from the extremities than body cores due to greater surface areas and distance from the heart. This relationship has been seen in analyses on bones from the modern Varanus komodoensis. On the other hand, true endothermic homeotherms should show a very narrow range of hetergeneity of δ18O values both within individual bones and between bones within single individuals as seen in modern mammals.
Dinosaurs analyzed indicate isotopic heterogeneities within individual bones intermediate between modern mammals and Varanus, with the Tyrannosaurus showing the greatest isotopic variability. However, this isotopic heterogeneity is relatively small and is not significantly different for bones from the body core and extremities. This indicates that heterogeneity of the δ18O values is most likely the result of variations in drinking water δ18O values throughout an individual's lifetime rather than daily or seasonal variations in body temperatures.