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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.
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 Iron Age of Mainland Southeast Asia began in the fifth century bc and lasted for about a millennium. In coastal regions, the development of trade along the Maritime Silk Road led to the growth of port cities. In the interior, a fall in monsoon rains particularly affected the Mun River valley. This coincided with the construction of moats/reservoirs round Iron Age settlements from which water was channelled into wet rice fields, the production of iron ploughshares and sickles, population growth, burgeoning exchange and increased conflict. We explore the social impact of this agricultural revolution through applying statistical analyses to mortuary samples dating before and after the development of wet rice farming. These suggest that there was a swift formation of social elites represented by the wealth of mortuary offerings, followed by a decline. Two associated changes are identified. The first involved burying the dead in residential houses; the second considers the impact of an increasingly aquatic environment on health by examining demographic trends involving a doubling of infant mortality that concentrated on neonates. A comparison between this sequence and that seen in coastal ports suggests two interconnected instances of rapid pathways to social change responding to different social and environmental stressors.
Salmonella enterica serovar Wangata (S. Wangata) is an important cause of endemic salmonellosis in Australia, with human infections occurring from undefined sources. This investigation sought to examine possible environmental and zoonotic sources for human infections with S. Wangata in north-eastern New South Wales (NSW), Australia. The investigation adopted a One Health approach and was comprised of three complimentary components: a case–control study examining human risk factors; environmental and animal sampling; and genomic analysis of human, animal and environmental isolates. Forty-eight human S. Wangata cases were interviewed during a 6-month period from November 2016 to April 2017, together with 55 Salmonella Typhimurium (S. Typhimurium) controls and 130 neighbourhood controls. Indirect contact with bats/flying foxes (S. Typhimurium controls (adjusted odds ratio (aOR) 2.63, 95% confidence interval (CI) 1.06–6.48)) (neighbourhood controls (aOR 8.33, 95% CI 2.58–26.83)), wild frogs (aOR 3.65, 95% CI 1.32–10.07) and wild birds (aOR 6.93, 95% CI 2.29–21.00) were statistically associated with illness in multivariable analyses. S. Wangata was detected in dog faeces, wildlife scats and a compost specimen collected from the outdoor environments of cases’ residences. In addition, S. Wangata was detected in the faeces of wild birds and sea turtles in the investigation area. Genomic analysis revealed that S. Wangata isolates were relatively clonal. Our findings suggest that S. Wangata is present in the environment and may have a reservoir in wildlife populations in north-eastern NSW. Further investigation is required to better understand the occurrence of Salmonella in wildlife groups and to identify possible transmission pathways for human infections.
Subclinical delusional ideas, including persecutory beliefs, in otherwise healthy individuals are heritable symptoms associated with increased risk for psychotic illness, possibly representing an expression of one end of a continuum of psychosis severity. The identification of variation in brain function associated with these symptoms may provide insights about the neurobiology of delusions in clinical psychosis.
A resting-state functional magnetic resonance imaging scan was collected from 131 young adults with a wide range of severity of subclinical delusional beliefs, including persecutory ideas. Because of evidence for a key role of the amygdala in fear and paranoia, resting-state functional connectivity of the amygdala was measured.
Connectivity between the amygdala and early visual cortical areas, including striate cortex (V1), was found to be significantly greater in participants with high (n = 43) v. low (n = 44) numbers of delusional beliefs, particularly in those who showed persistence of those beliefs. Similarly, across the full sample, the number of and distress associated with delusional beliefs were positively correlated with the strength of amygdala-visual cortex connectivity. Moreover, further analyses revealed that these effects were driven by those who endorsed persecutory beliefs.
These findings are consistent with the hypothesis that aberrant assignments of threat to sensory stimuli may lead to the downstream development of delusional ideas. Taken together with prior findings of disrupted sensory-limbic coupling in psychosis, these results suggest that altered amygdala-visual cortex connectivity could represent a marker of psychosis-related pathophysiology across a continuum of symptom severity.
We evaluated the performance of three serological tests – an immunoglobulin G indirect enzyme linked immunosorbent assay (iELISA), a Rose Bengal test and a slow agglutination test (SAT) – for the diagnosis of bovine brucellosis in Bangladesh. Cattle sera (n = 1360) sourced from Mymensingh district (MD) and a Government owned dairy farm (GF) were tested in parallel. We used a Bayesian latent class model that adjusted for the conditional dependence among the three tests and assumed constant diagnostic accuracy of the three tests in both populations. The sensitivity and specificity of the three tests varied from 84.6% to 93.7%, respectively. The true prevalences of bovine brucellosis in MD and the GF were 0.6% and 20.4%, respectively. Parallel interpretation of iELISA and SAT yielded the highest negative predictive values: 99.9% in MD and 99.6% in the GF; whereas serial interpretation of both iELISA and SAT produced the highest positive predictive value (PPV): 99.9% in the GF and also high PPV (98.9%) in MD. We recommend the use of both iELISA and SAT together and serial interpretation for culling and parallel interpretation for import decisions. Removal of brucellosis positive cattle will contribute to the control of brucellosis as a public health risk in Bangladesh.
We consider a family of nonlinear rational recurrences of odd order which was introduced by Heideman and Hogan, and recently rediscovered in the theory of Laurent phenomenon algebras (a generalization of cluster algebras). All of these recurrences have the Laurent property, implying that for a particular choice of initial data (all initial values set to 1) they generate an integer sequence. For these particular sequences, Heideman and Hogan gave a direct proof of integrality by showing that the terms of the sequence also satisfy a linear recurrence relation with constant coefficients. Here we present an analogous result for the general solution of each of these recurrences.
OBJECTIVES/SPECIFIC AIMS: The objective of the study was 2-fold; to identify potentially deleterious alleles in a child with Treacher Collins syndrome, and; to demonstrate the value of the iobio analysis platform for intuitively and rapidly analyzing genomic data. METHODS/STUDY POPULATION: We used the iobio suite of web-based applications to analyze quality metrics for the sequencing data and called variants for the proband and his parents. We then visually interrogated variants in genes potentially associated with the syndrome in real-time, using the intuitive gene.iobio application. We sought high impact variants that demonstrated a predicted impact on the protein function, and were simultaneously at low allele frequency in the general human population. Variants were also compared against the ClinVar database of known mutations to identify variants that have already been associated with this, or related syndromes in the literature or clinical studies. Finally, the gene.iobio tool allows users to interrogate the primary sequencing data to ensure that no variants had been missed by the primary variant calling pipeline. This analysis pipeline was performed using intuitive web-based apps in real time, and consequently represents a system that is available to users that traditionally are excluded from these analyses. RESULTS/ANTICIPATED RESULTS: The iobio suite was used to rapidly assess data quality and interrogate genetic variants for a child with Treacher Collins syndrome. A compound heterozygote consisting of 2 missense alleles in the TCOF1 gene was identified as a compelling pathogenic allele, necessitating further functional investigation. The study helped validate the use of the intuitive iobio tools in such analyses, strengthening the case for greater involvement of medical professionals in data analysis. DISCUSSION/SIGNIFICANCE OF IMPACT: The performed analyses demonstrated that the whole genome sequencing data for the family being studied was of a very high quality, although 1 gene demonstrated a local region of almost zero coverage. This ensured that study conclusions can be presented with confidence. A variant associated with Treacher Collins syndrome 1 in ClinVar was uncovered in the TCOF1 gene, however, given it’s benign rating, this variant was not considered further. The most interesting candidate was a compound heterozygote, consisting of 2 missense mutations, also in the TCOF1 gene. These mutations occurred with allele frequencies of 22% and 8% in the general population, and additional molecular and functional studies are currently being pursued.
OBJECTIVES/SPECIFIC AIMS: Platelets govern signal-dependent inflammatory responses by leukocytes. Although dysregulated inflammation is common in older adults, platelet-leukocyte signaling events and downstream inflammatory gene synthesis in aging is not known. METHODS/STUDY POPULATION: Highly-purified platelets and monocytes were isolated from healthy older (age>60, n=27) and younger (age<45, n=36) adults and incubated together in autologous and nonautologous conditions. Inflammatory gene synthesis by monocytes, basally and in the presence of activated platelets, was examined. Next-generation RNA-sequencing allowed for unbiased profiling of the platelet transcriptome in older and younger adults. Differentially expressed candidates in aged platelets were validated and recombinant granzyme A (in the presence and absence of TLR4 and Caspase-1 inhibition) identified putative ligands controlling inflammatory gene synthesis. RESULTS/ANTICIPATED RESULTS: In unstimulated or activated conditions, monocyte chemoattractant protein 1 (MCP-1) and interleukin-8 (IL-8) synthesis by monocytes alone did not differ between older and younger adults. However, in the presence of autologous activated platelets, monocytes from older adults synthesized significantly greater MCP-1 (867.150 vs. 216.36 ng/mL, p<0.0001) and IL-8 (41.5 vs. 9.2 ng/mL, p<0.0001) than younger adults. Nonautologous, or switch experiments, demonstrated that aged platelets were sufficient for upregulating MCP-1 and IL-8 synthesis by monocytes. Surprisingly, classic platelet proteins known to signal to monocytes and induce MCP-1 synthesis (p-selectin, RANTES, and PF4) were not increased in platelets from older adults. Using RNA-seq followed by validation via RT-PCR and immunoblot, we identified candidate platelet molecules increased in aging that mediate platelet-monocyte signaling and pro-inflammatory gene synthesis. We confirmed that granzyme A (GrmA), a serine protease not previously identified in platelets, is present in human platelets at the mRNA and protein level. GrmA is secreted by activated platelets in signal-dependent fashion. Moreover, GrmA in platelets is significantly increased in aging (~9-fold vs. younger adults). Blocking GrmA inhibited MCP-1 and IL-8 synthesis in older adults. Finally, we uncovered that platelet GrmA signaling to monocytes is regulated through TLR4 and Caspase-1. DISCUSSION/SIGNIFICANCE OF IMPACT: Human aging is associated with reprogramming of the platelet transcriptome. A previously unrecognized protein in platelets, GrmA, is increased in aging and causes increased MCP-1 and IL-8 gene synthesis by target monocytes in a TLR4 and Caspase-1 dependent mechanism. Increased platelet GrmA in aging may contribute to injurious inflammatory responses common in older adults.
OBJECTIVES/SPECIFIC AIMS: The iobio project enables anyone (eg, diagnosticians, MDs, genetic counselors, citizen scientists) to perform useful analysis of genomic data, without a need to rely on bioinformaticians. iobio uses a novel real-time analysis framework, coupled with powerful visualizations delivered in a standard web browser. The project successfully supports free academic/nonprofit users, but occasions exist where it is more applicable for the project to be delivered commercially. Frameshift Genomics is developing commercial applications and functionality, which will exist alongside and in coordination with the academic project. These products will be marketed to large institutions including genome institutes, hospitals, diagnostic labs etc., but also to individual users who do not have access to large compute resources, or bioinformatic analysts, and everything in between. METHODS/STUDY POPULATION: The commercial iobio project under Frameshift Genomics aims to develop applications and features that cannot be successfully supported by an academic model. For example, when analyses are scaled up to processing of extremely large data sets, a commercial product with access to compute resources makes more sense than an academic tool. Bam.iobio is an application that samples data from sequencing alignment files, taking seconds to generate and visualize statistics representative of the entire file. This app is offered for free academically. When analysis involves thousands of such files, however, the commercial application, multibam.iobio, is more suitable. Other examples, including support for licensed third-party software and permitting extensive computation via cloud platforms, can also only be reasonably be supported via commercial software. Finally, development of commercial applications is driving adoption of more rigorous testing platforms, delivering more robust products. A particular strength of the iobio platform is allowing non-bioinformaticians to understand their data, for example providing quality control functionality providing confidence in data sets and the conclusions drawn from them. Such analyses are critical to all users of genomic data, and the iobio platform is ideally suited to provide an intuitive, integrated framework for performing them. RESULTS/ANTICIPATED RESULTS: The iobio project has been readily adopted by many in the community and shows significant promise for democratizing genomic analysis. Work is ongoing, supported by NIH small business grants, to develop commercial applications that will be marketed to analysts and medical professionals from large genome institutes and universities, to individual project users and citizen scientists. DISCUSSION/SIGNIFICANCE OF IMPACT: There are currently a number of iobio tools available academically, and they have been embraced by many in the genomics community. In fact, a number of popular platforms (eg, Galaxy, the International Cancer Genome Consortium (ICGC) data portal, mygene2 at the University of Washington) have incorporated iobio tools into their own platforms. To date, the gene.iobio variant interrogation tool has been used in a number of diagnostic projects, aiding identification of putative causative variants, and the pre-release version of the commercial multibam.iobio tool has been critical in unearthing data quality problems in project level data.
In many regions of the world domestic dogs are free roaming and live in close relationship with humans. These free-roaming domestic dogs (FRDD) can cause public health problems such as dog bites and transmission of infectious diseases. To effectively control diseases transmitted by FRDD, knowledge on the dogs’ behaviour is required. To identify predictors of home range (HR) size, we collected global positioning system data from 135 FRDD living in eight Aboriginal and Torres Strait Islander communities in Northern Australia. The core HR size ranged from 0·17 to 2·33 ha and the extended HR size from 0·86 to 40·46 ha. Using a linear mixed effect model with a Restricted Maximum Likelihood approach, the dog's sex and reproductive status were identified as predictors of roaming. Non-castrated males had the largest HRs, followed by neutered females. Also, FRDDs were found to roam further during the pre- than the post-wet season. These findings have implications for infectious disease spread. Identification of risk groups for disease spread within a population allows for more targeted disease response and surveillance. Further investigation of predictors of roaming in other FRDD populations worldwide would increase the external validity of such studies.
Information about the health and economic impact of infections caused by vancomycin-resistant enterococci (VRE) can inform investments in infection prevention and development of novel therapeutics.
To systematically review the incidence of VRE infection in the United States and the clinical and economic outcomes.
We searched various databases for US studies published from January 1, 2000, through June 8, 2015, that evaluated incidence, mortality, length of stay, discharge to a long-term care facility, readmission, recurrence, or costs attributable to VRE infections. We included multicenter studies that evaluated incidence and single-center and multicenter studies that evaluated outcomes. We kept studies that did not have a denominator or uninfected controls only if they assessed postinfection length of stay, costs, or recurrence. We performed meta-analysis to pool the mortality data.
Five studies provided incidence data and 13 studies evaluated outcomes or costs. The incidence of VRE infections increased in Atlanta and Detroit but did not increase in national samples. Compared with uninfected controls, VRE infection was associated with increased mortality (pooled odds ratio, 2.55), longer length of stay (3-4.6 days longer or 1.4 times longer), increased risk of discharge to a long-term care facility (2.8- to 6.5-fold) or readmission (2.9-fold), and higher costs ($9,949 higher or 1.6-fold more).
VRE infection is associated with large attributable burdens, including excess mortality, prolonged in-hospital stay, and increased treatment costs. Multicenter studies that use suitable controls and adjust for time at risk or confounders are needed to estimate the burden of VRE infections.
Our objective was to estimate the per-infection and cumulative mortality and cost burden of multidrug-resistant (MDR) Acinetobacter healthcare-associated infections (HAIs) in the United States using data from published studies.
We identified studies that estimated the excess cost, length of stay (LOS), or mortality attributable to MDR Acinetobacter HAIs. We generated estimates of the cost per HAI using 3 methods: (1) overall cost estimates, (2) multiplying LOS estimates by a cost per inpatient-day ($4,350) from the payer perspective, and (3) multiplying LOS estimates by a cost per inpatient-day from the hospital ($2,030) perspective. We deflated our estimates for time-dependent bias using an adjustment factor derived from studies that estimated attributable LOS using both time-fixed methods and either multistate models (70.4% decrease) or matching patients with and without HAIs using the timing of infection (47.4% decrease). Finally, we used the incidence rate of MDR Acinetobacter HAIs to generate cumulative incidence, cost, and mortality associated with these infections.
Our estimates of the cost per infection were $129,917 (method 1), $72,025 (method 2), and $33,510 (method 3). The pooled relative risk of mortality was 4.51 (95% CI, 1.10–32.65), which yielded a mortality rate of 10.6% (95% CI, 2.5%–29.4%). With an incidence rate of 0.141 (95% CI, 0.136–0.161) per 1,000 patient-days at risk, we estimated an annual cumulative incidence of 12,524 (95% CI, 11,509–13,625) in the United States.
The estimates presented here are relevant to understanding the expenditures and lives that could be saved by preventing MDR Acinetobacter HAIs.
To characterize meal patterns across ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study.
Cross-sectional study utilizing dietary data collected through a standardized 24 h diet recall during 1995–2000. Eleven predefined intake occasions across a 24 h period were assessed during the interview. In the present descriptive report, meal patterns were analysed in terms of daily number of intake occasions, the proportion reporting each intake occasion and the energy contributions from each intake occasion.
Twenty-seven centres across ten European countries.
Women (64 %) and men (36 %) aged 35–74 years (n 36 020).
Pronounced differences in meal patterns emerged both across centres within the same country and across different countries, with a trend for fewer intake occasions per day in Mediterranean countries compared with central and northern Europe. Differences were also found for daily energy intake provided by lunch, with 38–43 % for women and 41–45 % for men within Mediterranean countries compared with 16–27 % for women and 20–26 % for men in central and northern European countries. Likewise, a south–north gradient was found for daily energy intake from snacks, with 13–20 % (women) and 10–17 % (men) in Mediterranean countries compared with 24–34 % (women) and 23–35 % (men) in central/northern Europe.
We found distinct differences in meal patterns with marked diversity for intake frequency and lunch and snack consumption between Mediterranean and central/northern European countries. Monitoring of meal patterns across various cultures and populations could provide critical context to the research efforts to characterize relationships between dietary intake and health.
Diarrhoeal diseases are major causes of morbidity and mortality in developing countries. This longitudinal study aimed to identify controllable environmental drivers of intestinal infections amidst a highly contaminated drinking water supply in urban slums and villages of Vellore, Tamil Nadu in southern India. Three hundred households with children (<5 years) residing in two semi-urban slums and three villages were visited weekly for 12–18 months to monitor gastrointestinal morbidity. Households were surveyed at baseline to obtain information on environmental and behavioural factors relevant to diarrhoea. There were 258 diarrhoeal episodes during the follow-up period, resulting in an overall incidence rate of 0·12 episodes/person-year. Incidence and longitudinal prevalence rates of diarrhoea were twofold higher in the slums compared to rural communities (P < 0·0002). Regardless of study site, diarrhoeal incidence was highest in infants (<1 year) at 1·07 episodes/person-year, and decreased gradually with increasing age. Increasing diarrhoeal rates were associated with presence of children (<5 years), domesticated animals and low socioeconomic status. In rural communities, open-field defecation was associated with diarrhoea in young children. This study demonstrates the contribution of site-specific environmental and behavioural factors in influencing endemic rates of urban and rural diarrhoea in a region with highly contaminated drinking water.
Two broad aims drive weed science research: improved management and improved
understanding of weed biology and ecology. In recent years, agricultural
weed research addressing these two aims has effectively split into separate
subdisciplines despite repeated calls for greater integration. Although some
excellent work is being done, agricultural weed research has developed a
very high level of repetitiveness, a preponderance of purely descriptive
studies, and has failed to clearly articulate novel hypotheses linked to
established bodies of ecological and evolutionary theory. In contrast,
invasive plant research attracts a diverse cadre of nonweed scientists using
invasions to explore broader and more integrated biological questions
grounded in theory. We propose that although studies focused on weed
management remain vitally important, agricultural weed research would
benefit from deeper theoretical justification, a broader vision, and
increased collaboration across diverse disciplines. To initiate change in
this direction, we call for more emphasis on interdisciplinary training for
weed scientists, and for focused workshops and working groups to develop
specific areas of research and promote interactions among weed scientists
and with the wider scientific community.