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Better understanding of interplay among symptoms, cognition and functioning in first-episode psychosis (FEP) is crucial to promoting functional recovery. Network analysis is a promising data-driven approach to elucidating complex interactions among psychopathological variables in psychosis, but has not been applied in FEP.
This study employed network analysis to examine inter-relationships among a wide array of variables encompassing psychopathology, premorbid and onset characteristics, cognition, subjective quality-of-life and psychosocial functioning in 323 adult FEP patients in Hong Kong. Graphical Least Absolute Shrinkage and Selection Operator (LASSO) combined with extended Bayesian information criterion (BIC) model selection was used for network construction. Importance of individual nodes in a generated network was quantified by centrality analyses.
Our results showed that amotivation played the most central role and had the strongest associations with other variables in the network, as indexed by node strength. Amotivation and diminished expression displayed differential relationships with other nodes, supporting the validity of two-factor negative symptom structure. Psychosocial functioning was most strongly connected with amotivation and was weakly linked to several other variables. Within cognitive domain, digit span demonstrated the highest centrality and was connected with most of the other cognitive variables. Exploratory analysis revealed no significant gender differences in network structure and global strength.
Our results suggest the pivotal role of amotivation in psychopathology network of FEP and indicate its critical association with psychosocial functioning. Further research is required to verify the clinical significance of diminished motivation on functional outcome in the early course of psychotic illness.
We use models incorporating the normalized difference vegetation index (NDVI) derived from remote sensing satellites to improve soybean yield predictions in 10 major producing states in the United States. Unlike traditional methods that assume an ordinary least squares model applies to all observations, we allow for global flexibility in the relationship between NDVI and soybean yield by using the flexible Fourier transform (FFT) model. FFT results confirm that there is a nonlinear response of soybean yield to NDVI over the growing season. Out-of-sample predictions indicate that allowing for global flexibility with the FFT improves the predictions in time-series prediction and forecasting.
Healthcare-associated infections (HAIs) are a significant burden on healthcare facilities. Universal gloving is a horizontal intervention to prevent transmission of pathogens that cause HAI. In this meta-analysis, we aimed to identify whether implementation of universal gloving is associated with decreased incidence of HAI in clinical settings.
A systematic literature search was conducted to find all relevant publications using search terms for universal gloving and HAIs. Pooled incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using random effects models. Heterogeneity was evaluated using the Woolf test and the I2 test.
In total, 8 studies were included. These studies were moderately to substantially heterogeneous (I2 = 59%) and had varied results. Stratified analyses showed a nonsignificant association between universal gloving and incidence of methicillin-resistant Staphylococcus aureus (MRSA; pooled IRR, 0.94; 95% CI, 0.79–1.11) and vancomycin-resistant enterococci (VRE; pooled IRR, 0.94; 95% CI, 0.69–1.28). Studies that implemented universal gloving alone showed a significant association with decreased incidence of HAI (IRR, 0.77; 95% CI, 0.67–0.89), but studies implementing universal gloving as part of intervention bundles showed no significant association with incidence of HAI (IRR, 0.95; 95% CI, 0.86–1.05).
Universal gloving may be associated with a small protective effect against HAI. Despite limited data, universal gloving may be considered in high-risk settings, such as pediatric intensive care units. Further research should be performed to determine the effects of universal gloving on a broader range of pathogens, including gram-negative pathogens.
The second Singapore Mental Health Study (SMHS) – a nationwide, cross-sectional, epidemiological survey - was initiated in 2016 with the intent of tracking the state of mental health of the general population in Singapore. The study employed the same methodology as the first survey initiated in 2010. The SMHS 2016 aimed to (i) establish the 12-month and lifetime prevalence and correlates of major depressive disorder (MDD), dysthymia, bipolar disorder, generalised anxiety disorder (GAD), obsessive compulsive disorder (OCD) and alcohol use disorder (AUD) (which included alcohol abuse and dependence) and (ii) compare the prevalence of these disorders with reference to data from the SMHS 2010.
Door-to-door household surveys were conducted with adult Singapore residents aged 18 years and above from 2016 to 2018 (n = 6126) which yielded a response rate of 69.0%. The subjects were randomly selected using a disproportionate stratified sampling method and assessed using World Health Organization Composite International Diagnostic Interview version 3.0 (WHO-CIDI 3.0). The diagnoses of lifetime and 12-month selected mental disorders including MDD, dysthymia, bipolar disorder, GAD, OCD, and AUD (alcohol abuse and alcohol dependence), were based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria.
The lifetime prevalence of at least one mood, anxiety or alcohol use disorder was 13.9% in the adult population. MDD had the highest lifetime prevalence (6.3%) followed by alcohol abuse (4.1%). The 12-month prevalence of any DSM-IV mental disorders was 6.5%. OCD had the highest 12-month prevalence (2.9%) followed by MDD (2.3%). Lifetime and 12-month prevalence of mental disorders assessed in SMHS 2016 (13.8% and 6.4%) was significantly higher than that in SMHS 2010 (12.0% and 4.4%). A significant increase was observed in the prevalence of lifetime GAD (0.9% to 1.6%) and alcohol abuse (3.1% to 4.1%). The 12-month prevalence of GAD (0.8% vs. 0.4%) and OCD (2.9% vs. 1.1%) was significantly higher in SMHS 2016 as compared to SMHS 2010.
The high prevalence of OCD and the increase across the two surveys needs to be tackled at a population level both in terms of creating awareness of the disorder and the need for early treatment. Youth emerge as a vulnerable group who are more likely to be associated with mental disorders and thus targeted interventions in this group with a focus on youth friendly and accessible care centres may lead to earlier detection and treatment of mental disorders.
OBJECTIVES/SPECIFIC AIMS: Prostate cancer is the second leading cause of cancer-related death among men in the U.S. and over half of all prostate cancer patients receive radiation therapy (RT). RT induces double-strand breaks (DSBs) in DNA which are lethal to cells if not repaired. While potentially curative, 10% of low-risk patients and 50% of high-risk patients treated with RT still experience tumor recurrence. Thus, identification of novel therapeutic targets to enhance RT will likely reduce prostate cancer mortality. The only clinical approach to enhance RT is androgen deprivation therapy, which targets androgen receptor (AR) signaling; however, its use is limited due to systemic side effects. We recently reported that PRMT5 epigenetically activates AR which led us to investigate if targeting PRMT5 sensitizes prostate cancer to RT. The goal of this project is to determine if PRMT5 is a therapeutic target for prostate cancer radiosensitization and analyze its mechanistic role in response to radiation. METHODS/STUDY POPULATION: To evaluate if targeting PRMT5 may sensitize prostate cancer cells to radiation, we performed a clonogenic assay of irradiated cells. To determine if PRMT5 is required for repair of radiation-induced DSBs, we performed foci analysis via immunocytochemistry. We then used RNA-seq, qPCR, western blot, and ChIP to evaluate a potential epigenetic role of PRMT5 in activating the expression of genes critical to DSB repair. To extend our findings, we analyzed clinical data from around 18,000 of cancer patients encompassing 43 cancer types to assess if PRMT5 expression correlates with the expression of its putative target genes. RESULTS/ANTICIPATED RESULTS: Targeting PRMT5 sensitizes prostate cancer cells to radiation independently of AR status. RNA-seq analysis revealed putative PRMT5 target genes including several involved in DSB repair and G2 arrest. Mechanistically, PRMT5 functions as a master epigenetic activator of DNA damage response (DDR) genes: PRMT5 maintains the basal expression of several DDR genes including BRCA1, BRCA2, and RAD51 and is recruited upon radiation to DDR gene promoters to activate their expression via histone methylation. Targeting PRMT5 decreases expression of these genes at the protein level and hinders repair of radiation-induced DSBs in multiple cancer and non-cancer cell types. Clinically, PRMT5 expression positively correlates with the expression of these DDR genes across all 43 cancer types analyzed. DISCUSSION/SIGNIFICANCE OF IMPACT: PRMT5 acts as a master epigenetic activator of genes involved in DDR and is critical for cells to survive radiation treatment. Importantly, PRMT5 epigenetically activates multiple genes that encode for well-characterized core repair proteins involved in HR (RAD51, RAD51AP1, RAD51D, BRCA1 and BRCA2) and NHEJ (NHEJ1, Ku80, XRCC4, and DNAPKcs), which may explain why PRMT5 is essential to repair IR-induced DSBs in several cell lines. As PRMT5 is overexpressed in many human cancers and its overexpression correlates with poor prognosis, our findings suggest that more efficient DSB repair via PRMT5 overexpression in these cancers may confer survival advantages particularly following DNA damaging treatments. Lastly, because targeting DSB repair is a clinically validated therapeutic approach for cancer treatment, our findings also suggest that PRMT5 targeting may be explored as a monotherapy or in combination therapy with radiation therapy or chemotherapy for cancer treatment.
Plant nitrogen (N) links with many physiological progresses of crop growth and yield formation. Accurate simulation is key to predict crop growth and yield correctly. The aim of the current study was to improve the estimation of N uptake and translocation processes in the whole rice plant as well as within plant organs in the RiceGrow model by using plant and organ maximum, critical and minimum N dilution curves. The maximum and critical N (Nc) demand (obtained from the maximum and critical curves) of shoot and root and Nc demand of organs (leaf, stem and panicle) are calculated by N concentration and biomass. Nitrogen distribution among organs is computed differently pre- and post-anthesis. Pre-anthesis distribution is determined by maximum N demand with no priority among organs. In post-anthesis distribution, panicle demands are met first and then the remaining N is allocated to other organs without priority. The amount of plant N uptake depends on plant N demand and N supplied by the soil. Calibration and validation of the established model were performed on field experiments conducted in China and the Philippines with varied N rates and N split applications; results showed that this improved model can simulate the processes of N uptake and translocation well.
Nasal irrigation is commonly performed in patients with chronic rhinosinusitis after functional endoscopic sinus surgery. This study systematically assessed the clinical efficacy of nasal irrigation from the medical literature.
The PubMed, Embase and Cochrane Central Register of Controlled Trials databases were searched using a comprehensive strategy, limited to English-language articles, published from October 1971 to March 2017, and comprising human subjects.
A total of 824 trials were identified, 5 of which, involving 331 participants, were included in this systematic review. After selection, only three trials were eligible for inclusion in a meta-analysis. Nasal irrigation using normal saline and various solutions was found to be effective in reducing symptom scores and endoscopic scores for chronic rhinosinusitis patients after functional endoscopic sinus surgery. Comparison of outcome measures, such as eosinophil count reduction, revealed that various solutions are more effective than normal saline alone; however, no statistical significance was found in terms of reduced symptom or endoscopic scores.
Based on the current limited evidence, nasal irrigation is an effective therapy for chronic rhinosinusitis patients after functional endoscopic sinus surgery. However, when comparing various solutions with normal saline, no significant difference was found in symptom scores or endoscopic scores.
OBJECTIVES/SPECIFIC AIMS: “Cure Quest” is an adventure quest game for mobile tablets that aims to teach the player about the complexities of discovery and development of new medicines. The game instills a sense of wonderment into the learning process, taking the player to a world of magic where a mysterious condition has affected the land and they must follow the steps of the discovery and development process to find a treatment. METHODS/STUDY POPULATION: The game is being developed through a collaboration between faculty and students at ISMMS and the Games and Simulation Arts and Science Program at Rensselaer Polytechnic Institute. The first target audience is 2nd–3rd year medical students, with the future goal of adapting the game to a broader population. RESULTS/ANTICIPATED RESULTS: The game is currently in development, but the project has yielded insight into the design process for serious games in medicine. We found that for a game of this type it is essential not just to have both designers and subject matter experts, but to enable cross-pollination of modes of thinking. Through multiple design iterations and focus groups, we found that a game design approach rooted in narrative and allegorical abstraction would have a better ability to engage the target audience than one focused only on realistic simulation. When complete, we anticipate that the game will improve understanding of the core concepts in drug discovery. DISCUSSION/SIGNIFICANCE OF IMPACT: If successful, the game-based learning approach can help fill key gaps in current formal medical and scientific training, as well as gaps in understanding among the general public. The design process serves as an informative model of evolving collaborative team science.
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.
Knowledge, attitudes and practices (KAP) of the population regarding severe fever with thrombocytopenia syndrome (SFTS) in endemic areas of Lu'an in China were assessed before and after an intervention programme. The pre-intervention phase was conducted using a sample of 425 participants from the 12 selected villages with the highest rates of endemic SFTS infection. A predesigned interview questionnaire was used to assess KAP. Subsequently, an intervention programme was designed and applied in the selected villages. KAP was re-assessed for each population in the selected villages using the same interview questionnaire. Following 2 months of the programme, 339 participants had completed the re-assessed survey. The impact of the intervention programme was evaluated using suitable statistical methods. A significant increase in the KAP and total KAP scores was noted following the intervention programme, whereas the proportion of correct knowledge, the positive attitudes and the effective practices toward SFTS of respondents increased significantly. The intervention programme was effective in improving KAP level of SFTS in populations that were resident in endemic areas.
In anticipation of the launch of the Earth Observing System (EOS) Terra, and the Aqua spacecraft in 1999 and 2000, respectively, efforts are ongoing to determine errors of satellite-derived snow-cover maps. EOS Moderate Resolution Imaging Spectrora-diometer (MODIS) and Advanced Microwave Scanning Radiometer-E (AMSR-E) snow-cover products will be produced. For this study we compare snow maps covering the same study areas in Canada and the United States, acquired from different sensors using different snow-mapping algorithms. Four locations are studied: (1) Saskatchewan, Canada; (2) New England (New Hampshire, Vermont and Massachusetts) and eastern New York; (3) central Idaho and western Montana; and (4) North and South Dakota. Snow maps were produced using a prototype MODIS snow-mapping algorithm from Landsat Thematic Mapper (TM) scenes of each study area at 30 m and when the TM data were degraded to 1 km resolution. U.S. National Operational Hydrologic Remote Sensing Center (NOHRSC) 1km resolution snow maps were also used, as were snow maps derived from 0.5° × 0.5° resolution Special Sensor Microwave Imager (SSM/I) data. A land-cover map derived from the International Geosphere-Biosphere Program land-cover map of North America was also registered to the scenes. The TM, NOHRSC and SSM/ I snow maps, and land-cover maps were compared digitally. In most cases, TM-derived maps show less snow cover than the NOHRSC and SSM/I maps because areas of incomplete snow cover in forests (e.g. tree canopies, branches and trunks) are seen in the TM data but not in the coarser-resolution maps which may map the areas as completely snow-covered. The snow maps generally agree with respect to the spatial variability of the snow cover. The 30 m resolutionTM data provide the most accurate snow maps, and are thus used as the baseline for comparison with the other maps. Results show that the changes in amount of snow cover, as compared to to the 30 m resolution TM maps, are lowest using the TM 1km resolution maps, at 0–40%. The greatest change (>100%) is found in the New England study area, probably due to the presence of patchy snow cover. A scene with patchy snow cover is more difficult to map accurately than is a scene with a well-defined snowline such as is found on the North and South Dakota scene where the changes were 0–40%. There are also some important differences in the amount of snow mapped using the two different SSM/I algorithms because they utilize different channels.
There are several hemispheric-scale satellite-derived snow-cover maps available, but none has been fully validated. For the period 23 October–25 December 2000, we compare snow maps of North America derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) and operational snow maps from the U.S. National Oceanic and Atmospheric Administration (NOAA) National Operational Hydrologic Remote Sensing Center (NOHRSC), both of which rely on satellite data from the visible and near-infrared parts of the spectrum; we also compare MODIS maps with Defense Meteorological Satellite Program (DMSP) Special Sensor Microwave/Imager (SSM/I) passive-microwave snow maps for the same period. The maps derived from visible and near-infrared data are more accurate for mapping snow cover than are the passive-microwave-derived maps, but discrepancies exist as to the location and extent of the snow cover even between operational snow maps. The MODIS snow-cover maps show more snow in each of the 8 day periods than do the NOHRSC maps, in part because MODIS maps the effects of fleeting snowstorms due to its frequent coverage. The large (~30 km) footprint of the SSM/I pixel, and the difficulty in distinguishing wet and shallow snow from wet or snow-free ground, reveal differences up to 5.33 x 106 km2 in the amount of snow mapped using MODIS vs SSM/I data. Algorithms that utilize both visible and passive-microwave data, which would take advantage of the all-weather mapping capability of the passive-microwave data, will be refined following the launch of the Advanced Microwave Scanning Radiometer (AMSR) in the fall of 2001.
Lattice Boltzmann method (LBM) is adopted to compute two and three-dimensional lid driven cavity flows to examine the influence of memory management on the computational performance using Graphics Processing Unit (GPU). Both single and multi-relaxation time LBM are adopted. The computations are conducted on nVIDIA GeForce Titan, Tesla C2050 and GeForce GTX 560Ti. The performance using global memory deteriorates greatly when multi relaxation time (MRT) LBM is used, which is due to the scheme requesting more information from the global memory than its single relaxation time (SRT) LBM counterpart. On the other hand, adopting on chip memory the difference using MRT and SRT is not significant. Also, performance of LBM streaming procedure using offset reading surpasses offset writing ranging from 50% to 100% and this applies to both SRT and MRT LBM. Finally, comparisons using different GPU platforms indicate that Titan as expected outperforms other devices, and attains 227 and 193 speedup over its Intel Core i7-990 CPU counterpart and four times faster than GTX 560Ti and Tesla C2050 for three dimensional cavity flow simulations respectively with single and double precisions.
This research targets investigation of the internal elastic field near the boundaries of 3D anisotropic bodies by the boundary element method (BEM). This analysis appears to be most important, especially for the interest in the internal solutions near corners or crack tips, where structural failure is most likely to occur. Although the BEM is very efficient for analyzing the problem, nearly singular integration will arise when the internal point of interest stays near the boundary. The present work is to show how the self-regularized boundary integral equation (BIE) can be applied to the interior analysis for 3D generally anisotropic bodies. So far, to the authors' best knowledge, no implementation work has been reported in the literature for successfully treating the near boundary solutions in 3D generally anisotropic solids. In the end, a few benchmark examples are presented to demonstrate the veracity of the present approach for the interior BEM analysis of 3D anisotropic elasticity.