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Many studies document cognitive decline following specific types of acute illness hospitalizations (AIH) such as surgery, critical care, or those complicated by delirium. However, cognitive decline may be a complication following all types of AIH. This systematic review will summarize longitudinal observational studies documenting cognitive changes following AIH in the majority admitted population and conduct meta-analysis (MA) to assess the quantitative effect of AIH on post-hospitalization cognitive decline (PHCD).
We followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Selection criteria were defined to identify studies of older age adults exposed to AIH with cognitive measures. 6566 titles were screened. 46 reports were reviewed qualitatively, of which seven contributed data to the MA. Risk of bias was assessed using the Newcastle–Ottawa Scale.
The qualitative review suggested increased cognitive decline following AIH, but several reports were particularly vulnerable to bias. Domain-specific outcomes following AIH included declines in memory and processing speed. Increasing age and the severity of illness were the most consistent risk factors for PHCD. PHCD was supported by MA of seven eligible studies with 41,453 participants (Cohen’s d = −0.25, 95% CI [−0.02, −0.49] I2 35%).
There is preliminary evidence that AIH exposure accelerates or triggers cognitive decline in the elderly patient. PHCD reported in specific contexts could be subsets of a larger phenomenon and caused by overlapping mechanisms. Future research must clarify the trajectory, clinical significance, and etiology of PHCD: a priority in the face of an aging population with increasing rates of both cognitive impairment and hospitalization.
OBJECTIVES/GOALS: In this study, we established a high-throughput chemical screening platform to identify small molecules that facilitates efficient differentiation of stem cells derived β (SC-β) cells. Using this platform, we identified several compounds that potentially increase the differentiation efficiency. METHODS/STUDY POPULATION: Differentiation of human embryonic stem cells (HUES8) into SC-β was carried out using previously published protocols in a 3D cell suspension. Single cells were replated in Matrigel-coated well plates at the start of different stages depending on experiments. Differentiation medium supplemented with small molecules at a final concentration of 2 M and 0.2 M was used throughout the stage. All the cells were then fixed and permeabilized. Immunocytochemical staining was performed. Images of each well were taken and analyzed. Numbers of the total cell, insulin-positive cell, NKX6.1-positive cell, and co-positive cell were recorded. Candidate compounds were validated using flow cytometry or ICC. RESULTS/ANTICIPATED RESULTS: We identified several hit compounds that significantly increase the NKX6.1 positive cell percentage compared to the DMSO-treated controls when treated at the PP1 cell stage. Follow up assays demonstrated that at least one of these putative hits reproducibly increased NKX6.1 expression. In addition, we identified other compounds that significantly increase the insulin and NKX6.1 copositive SC-β cell population when treated at the later PP2 cell stage during the differentiation. We expect a dosage-dependent response when the candidate hits are validated using more accurate assays. DISCUSSION/SIGNIFICANCE OF IMPACT: We established a high-throughput screening platform to identify small molecules that increase the efficiency of SC-β direct differentiation. Successful generation of SC-β allows cell replacement therapy in diabetes patients, and a better understanding of pancreatic biology and development.
Basic Self disturbances (BSD), including changes of the 'pre-reflexive' sense of self and the loss first-person perspective, are characteristic of the schizophrenic spectrum disorders and highly prevalent in subjects at 'ultra high risk' for psychosis (UHR). The current literature indicates that cortical midline structures (CMS) may be implicated in the neurobiological substrates of the 'basic self' in healthy controls.
Neuroanatomical investigation of BSD in a UHR sample
To test the hypotheses :(i) UHR subjects have higher 'Examination of Anomalous Self Experience, EASE' scores as compared to controls, (ii) UHR subjects have neuroanatomical alterations as compared to controls in CMS, (iii) within UHR subjects, EASE scores are directly related to structural CMS alterations.
32 HR subjects (27 antipsychotics-naïve) and 17 healthy controls (HC) were assessed with the 57-items semi-structured EASE interview. Voxel-Based Morphometry (VBM) was conducted in the same subjects, with a-priori Region of Interests (ROIs) defined in the CMS (anterior/posterior cingulate and medial-prefrontal cortex).
Despite high variability in the HR group, the overall EASE score was higher (t-test >0.01, Cohen's d =2.91) in HR (mean=30.15, SD=16.46) as compared to HC group (mean=1.79, SD=2.83). UHR subjects had gray matter reduction in CMS as compared to HC (p>0.05 FWE-corrected). Across the whole sample, lower gray matter volume in the anterior cingulate was correlated with higher EASE scores (p>0.05).
This study provides preliminary evidence that gray matter reductions in the CMS are correlated with BSD in UHR people.
Q fever (caused by Coxiella burnetii) is thought to have an almost world-wide distribution, but few countries have conducted national serosurveys. We measured Q fever seroprevalence using residual sera from diagnostic laboratories across Australia. Individuals aged 1–79 years in 2012–2013 were sampled to be proportional to the population distribution by region, distance from metropolitan areas and gender. A 1/50 serum dilution was tested for the Phase II IgG antibody against C. burnetii by indirect immunofluorescence. We calculated crude seroprevalence estimates by age group and gender, as well as age standardised national and metropolitan/non-metropolitan seroprevalence estimates. Of 2785 sera, 99 tested positive. Age standardised seroprevalence was 5.6% (95% confidence interval (CI 4.5%–6.8%), and similar in metropolitan (5.5%; 95% CI 4.1%–6.9%) and non-metropolitan regions (6.0%; 95%CI 4.0%–8.0%). More males were seropositive (6.9%; 95% CI 5.2%–8.6%) than females (4.2%; 95% CI 2.9%–5.5%) with peak seroprevalence at 50–59 years (9.2%; 95% CI 5.2%–13.3%). Q fever seroprevalence for Australia was higher than expected (especially in metropolitan regions) and higher than estimates from the Netherlands (2.4%; pre-outbreak) and US (3.1%), but lower than for Northern Ireland (12.8%). Robust country-specific seroprevalence estimates, with detailed exposure data, are required to better understand who is at risk and the need for preventive measures.
The Square Kilometre Array (SKA) is a planned large radio interferometer designed to operate over a wide range of frequencies, and with an order of magnitude greater sensitivity and survey speed than any current radio telescope. The SKA will address many important topics in astronomy, ranging from planet formation to distant galaxies. However, in this work, we consider the perspective of the SKA as a facility for studying physics. We review four areas in which the SKA is expected to make major contributions to our understanding of fundamental physics: cosmic dawn and reionisation; gravity and gravitational radiation; cosmology and dark energy; and dark matter and astroparticle physics. These discussions demonstrate that the SKA will be a spectacular physics machine, which will provide many new breakthroughs and novel insights on matter, energy, and spacetime.
South-west Transylvania was an important source of metal and other natural resources for Bronze Age Europe, helping to facilitate the development of increasingly hierarchical societies. The absence of a radiocarbon-based chronology for Transylvania, however, has impeded understanding of the region's role within broader socioeconomic networks. Here, the presentation of the first radiocarbon chronology for the Wietenberg Culture in south-west Transylvania allows the authors to highlight the importance of interregional exchange and reliable access to metal for Bronze Age European societies, and emphasise that resource-procurement zones follow unique trajectories of socioeconomic organisation.
A 32-year-old male presented to the emergency department for confusion, dyspnea, and a “white out” of his central vision over the preceding 24 hours. The patient had recently consumed a bottle of alcohol purchased overseas. Bloodwork revealed a severe metabolic acidosis (pH 6.90) and a critically high methanol level of 28.9 mmol/l. Shortly after presentation, the patient went into respiratory failure and became comatose. He was intubated and admitted to the ICU.
As archaeologists expand the accessibility of legacy data, they have an opportunity to use these datasets to design future research. We argue that legacy data can be a critical resource to help predict characteristics of sites and socioeconomic systems. In this article, we present a combined geographic information system (GIS) and network analysis methodology that turns site location data into testable hypotheses about site characteristics and the organization of regional settlement systems. We demonstrate the utility of this approach with a case study: Bronze Age (2700–1100 BC) settlement patterns in the mining region of Hunedoara in southwest Transylvania, Romania. We leverage unsystematically collected site location information in legacy datasets to develop testable predictions about sites, regional networks, and socioeconomic systems that can be evaluated through future systematic surveys and large-scale excavations. Such testable hypotheses can inform archaeological research design by providing a quantitative basis for determining where to focus research efforts and can also help secure funding and fieldwork permits. The method developed here can be applied in diverse archaeological contexts to reinvigorate legacy data as part of future archaeological research design.
Hafting is an important part of lithic technology that can increase our understanding of socioeconomic behavior in the past. In this article, we develop a holistic approach to studying hafting by using the concept of curation within a broader assessment of lithic technological organization in early villages. Early villages were loci of socioeconomic transformation as part of the shift from mobile foraging to more sedentary cultivation lifeways. We suggest that an examination of hafting can provide new insights into how early villagers negotiated technological requirements, economic decision making, and social interactions in these novel contexts. As a case study, we develop a curation index and apply it to an archaeological context of hafted and unhafted pointed tools from the early Neolithic village of Dhra’, Jordan. This curation index allows for a discussion of the technological, economic, and social dimensions of hafting strategies at Dhra’. The presence of multiple hafting traditions within early Neolithic villages of Southwest Asia is evidence of persistent social segmentation despite food storage and ritual practices that emphasized communal integration. Through the lens of lithic technological organization, we demonstrate that hafting and curation patterns can increase our understanding of technological, economic, and social strategies in early villages.
This paper reviews the efficacy of a community psychosocial arts program focused on building mental health capacity within post-Ebola Liberia. The aim of this paper was to evaluate the outcome effects of two groups using pre- and post-treatment data. We hypothesized that there would be a difference in symptoms pre- and post-treatment, and the longer program would yield more significant results.
There was a total of 870 child participants. Of 40 sites, 24 were selected for a 5-month treatment (TG1) while the remaining 16 sites received 3 months of treatment (TG2). Paired t tests and a mixed-model analysis of variance (ANOVA) were used to analyse pre- and post-psychological stress symptoms (PSS) for samples from both groups.
Separately, treatment group 1 (TG1) and treatment group 2's (TG2) paired t test yielded significant results (p < 0.001) for the decrease of PSS. The mixed-model ANOVA found that there were significant differences in total pre- and post-test PSS and a significant difference in PSS means over time.
Results indicated that there was a statistically significant decrease in reported symptoms in both treatment groups pre- to post-intervention and a significant difference in total symptoms over time. However, the findings do not indicate that the longer programming was statistically different compared to the shorter programming. The study presented had gaps in data, largely due to limits in research during the crisis. However, this paper provides a unique case study for challenges that can be faced for project evaluation in emergency settings.
We describe the motivation and design details of the ‘Phase II’ upgrade of the Murchison Widefield Array radio telescope. The expansion doubles to 256 the number of antenna tiles deployed in the array. The new antenna tiles enhance the capabilities of the Murchison Widefield Array in several key science areas. Seventy-two of the new tiles are deployed in a regular configuration near the existing array core. These new tiles enhance the surface brightness sensitivity of the array and will improve the ability of the Murchison Widefield Array to estimate the slope of the Epoch of Reionisation power spectrum by a factor of ∼3.5. The remaining 56 tiles are deployed on long baselines, doubling the maximum baseline of the array and improving the array u, v coverage. The improved imaging capabilities will provide an order of magnitude improvement in the noise floor of Murchison Widefield Array continuum images. The upgrade retains all of the features that have underpinned the Murchison Widefield Array’s success (large field of view, snapshot image quality, and pointing agility) and boosts the scientific potential with enhanced imaging capabilities and by enabling new calibration strategies.
This article presents the results of multi-scalar investigations into the Later Bronze Age (LBA; 1500–600 bc) landscape of Inishark in County Galway, Ireland. The European LBA along the Atlantic coast was characterized by the development of long-distance maritime exchange systems that transformed environmentally marginal seascapes into a corridor of human interaction and movement of goods and people. Archaeological survey, test excavation, and radiocarbon analysis documented the LBA occupation on Inishark. The communities living on Inishark and other small islands on the western Irish coast were on the periphery of both the European continent and of the elite spheres of influence at hillforts in Ireland; yet they were connected to the Atlantic maritime exchange routes. A focus on small coastal islands contributes to a better understanding of LBA socioeconomic systems and the development of social complexity in Bronze Age societies.
n-3 Fatty acids, flavonoids and resveratrol are well publicised for their beneficial effects on human health and wellbeing. Identifying common, underlying biological mechanisms targeted by these functional foods would therefore be informative for the public health sector for advising on nutritional health and disease, food and drug product development and consumer interest. The aim of this study was to explore the potential effects of gene expression changes associated with n-3 fatty acids EPA and DHA, flavonoids and resveratrol on modifying biological systems and disease pathways. To test this, publicly available human microarray data for significant gene expression changes associated with dietary intervention with EPA/DHA, flavonoids and resveratrol was subjected to pathway analysis and significance testing for overlap with signals from genome-wide association studies (GWAS) for common non-communicable diseases and biological functions. There was an enrichment of genes implicated in immune responses and disease pathways which was common to all of the treatment conditions tested. Analysis of biological functions and disease pathways indicated anti-tumorigenic properties for EPA/DHA. In line with this, significance testing of the intersection of genes associated with these functional foods and GWAS hits for common biological functions (ageing and cognition) and non-communicable diseases (breast cancer, CVD, diabesity, neurodegeneration and psychiatric disorders) identified significant overlap between the EPA/DHA and breast cancer gene sets. Dietary intervention with EPA/DHA, flavonoids and resveratrol can target important biological and disease pathways suggesting a potentially important role for these bioactive compounds in the prevention and treatment of dietary-related diseases.
International trade directly influences US presidential elections. We explore the electoral implications of the increasing tradability of services and the large US surplus in services trade. Our paper builds on prior work showing that job insecurity from import competition in manufacturing diminishes political support for incumbents. We construct novel measures of the tradability of an industry using establishment-level data covering nearly all US economic activity. We find increases in incumbent party vote shares in counties with large numbers of workers in high-skilled tradable services as well as goods, and decreases in counties with high employment in low-skilled manufacturing. Incumbent parties are particularly vulnerable to losing votes in swing states with many low-skilled manufacturing workers. In national-level models, we show for the first time that increasing imports (exports) are associated with decreasing (increasing) presidential incumbent vote shares. The national-level effects are large and politically consequential. We also find an Electoral College incentive to protect the manufacturing sector and to oppose trade agreements.
During May 2015, an increase in Salmonella Agona cases was reported from western Sydney, Australia. We examine the public health actions used to investigate and control this increase. A descriptive case-series investigation was conducted. Six outbreak cases were identified; all had consumed cooked tuna sushi rolls purchased within a western Sydney shopping complex. Onset of illness for outbreak cases occurred between 7 April and 24 May 2015. Salmonella was isolated from food samples collected from the implicated premise and a prohibition order issued. No further cases were identified following this action. Whole genome sequence (WGS) analysis was performed on isolates recovered during this investigation, with additional S. Agona isolates from sporadic-clinical cases and routine food sampling in New South Wales, January to July 2015. Clinical isolates of outbreak cases were indistinguishable from food isolates collected from the implicated sushi outlet. Five additional clinical isolates not originally considered to be linked to the outbreak were genomically similar to outbreak isolates, indicating the point-source contamination may have started before routine surveillance identified an increase. This investigation demonstrated the value of genomics-guided public health action, where near real-time WGS enhanced the resolution of the epidemiological investigation.
Introduction: Patients presenting to the Emergency Department (ED) may require clarification of their goals of care (GOC) to ensure they receive treatments aligned with their values. However, these discussions can be difficult to conduct for multiple reasons, including lack of time in a busy ED, competing priorities and a limited relationship with the patient. Few studies have examined the perceived challenges faced by Emergency Physicians in conducting GOC discussions. This study sought to contextualize and discern the barriers and facilitators to having these conversations as reported by Emergency physicians. Methods: An interdisciplinary team of Emergency Medicine, Palliative Care and Internal Medicine providers developed an online survey comprised of multiple choice, Likert-scale and open-ended questions to explore four domains of GOC discussions: training; communication; environment; and personal beliefs. Invitations and scheduled reminders were sent to 275 ED physicians at six academic sites in a Canadian urban centre, including 49 EM residents. Results: 105 (46%) staff physicians and 23 (47%) residents responded with similar representation from all sites. Differences were reported in the frequency of GOC discussions: 59% of staff physicians conduct several per month whereas 65% of residents conduct less than one per month. Most agreed that GOC discussions are within their scope of practice (92%), they feel comfortable (96%), and are adequately trained (73%) to have them; however, 66% reported difficulty initiating GOC discussions. 73% believed that admitting services should conduct GOC discussions, yet acuity was noted in the comments as a major determinant with initiating GOC discussions by ED physicians. Main barriers identified were lack of time, chaotic environment, lack of advanced directives and the inability to reach substitute decision makers. 54% of respondents indicated that the availability of 24-hour Palliative Care consults would facilitate GOC discussions in the ED. Conclusion: Emergency physicians are prepared to conduct goals of care discussions, but often believe they should instead be conducted by the patient’s admitting service. Multiple perceived barriers to goals of care discussion in the ED were identified, and a majority of respondents felt that the availability of Palliative Care in the ED may facilitate these discussions.