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Although dementia is a terminal condition, palliation can be a challenge for clinical services. As dementia progresses, people frequently develop behavioural and psychological symptoms, sometimes so severe they require care in specialist dementia mental health wards. Although these are often a marker of late disease, there has been little research on the mortality of people admitted to these wards.
Aims
We sought to describe the mortality of this group, both on-ward and after discharge, and to investigate clinical features predicting 1-year mortality.
Method
First, we conducted a retrospective analysis of 576 people with dementia admitted to the Cambridgeshire and Peterborough National Health Service (NHS) Foundation Trust dementia wards over an 8-year period. We attempted to identify predictors of mortality and build predictive machine learning models. To investigate deaths occurring during admission, we conducted a second analysis as a retrospective service evaluation involving mental health wards for people with dementia at four NHS trusts, including 1976 admissions over 7 years.
Results
Survival following admission showed high variability, with a median of 1201 days (3.3 years). We were not able to accurately predict those at high risk of death from clinical data. We found that on-ward mortality remains rare but had increased from 3 deaths per year in 2013 to 13 in 2019.
Conclusions
We suggest that arrangements to ensure effective palliation are available on all such wards. It is not clear where discussions around end-of-life care are best placed in the dementia pathway, but we suggest it should be considered at admission.
Many studies have highlighted the detrimental effect of childhood maltreatment (CM) on depression severity and the course of illness in major depressive disorder (MDD). Yet our understanding of how CM influences the dynamic symptom change throughout a patient’s trajectory remains limited. Hence, we investigated the impact of CM on depression severity in MDD with a focus on various treatment phases during inpatient treatment and after discharge (1 or 2 years later) and validated findings in a real-world setting.
Methods
We used longitudinal data from a cohort study sample (n = 567) and a clinical routine sample (n = 438). CM was measured with the Childhood Trauma Questionnaire (CTQ), and depression severity was assessed using Beck’s Depression Inventory (BDI). The long-term clinical trajectory was assessed using the Life Chart Interview.
Results
Our analyses revealed that CM significantly increased depression severity before, during, and after inpatient therapy in both samples. Although CM was associated with higher depression severity at the beginning of inpatient treatment and lower remission rates upon discharge, no discernible impact of CM was evident on the relative change in symptoms over time during inpatient treatment. CM consistently predicted higher relapse rates and lower rates of full remission after discharge during long-term follow-up in both samples.
Conclusions
Our findings affirm the link between CM and the development of more severe and persistent clinical trajectories within real-world clinical settings. Furthermore, conventional psychiatric treatments may not lead to comparable outcomes for individuals with a history of CM, underscoring the necessity for tailored therapeutic interventions.
Objectives/Goals: Mathematical models of airborne virus transmission lack supporting field and clinical data such as viral aerosol emission rates and airborne infectious doses. Here, we aim to measure inhalation exposure to influenza aerosols in a room shared with persons with community-acquired influenza and estimate the infectious dose via inhalation. Methods/Study Population: We recruited healthy volunteer recipients and influenza donors with polymerase chain reaction (PCR)-confirmed community-acquired infection. On admission to a hotel quarantine, recipients provided sera to determine baseline immunity to influenza virus, and donor infections were confirmed by quantitative real-time polymerase chain reaction. Donors and recipients were housed in separate rooms and interacted in an “event room” with controlled ventilation (0.2 – 0.5 air changes/hour) and relative humidity (20–40%). We collected ambient bioaerosol exposure samples using NIOSH BC-251 samplers. Donors provided exhaled breath samples collected by a Gesundheit-II (G-II). We analyzed aerosol samples using dPCR and fluorescent focus assays for influenza A and sera by hemagglutinin inhibition assay (HAI) against donor viruses and vaccine strains. Results/Anticipated Results: Among two cohorts (24b and 24c), we exposed 11 recipients (mean age: 36; 55% female) to 5 donors (mean age: 21; 80% female) infected with influenza A H1N1 or H3N2. Eight G-II and two NIOSH bioaerosol samples (1–4 µm and ≥4 µm) were PCR positive. We cultured virus from one G-II sample. Based on previous literature, we hypothesized that ~50% of immunologically naïve people (HAI Discussion/Significance of Impact: We demonstrated that it is feasible to recruit donors with community-acquired influenza and expose recipients to measurable virus quantities under controlled conditions. However, baseline immunity was high among volunteers. Our work sets the stage for designing studies with increased sample sizes comprising immunologically naïve volunteers.
Water hyacinth is a highly invasive aquatic species in the southern United States that requires intensive management through frequent herbicide applications. Quantifying management success in large-scale operations is challenging with traditional survey methods that rely on boat-based teams and can be time-consuming and labor-intensive. In contrast, an unmanned aerial system (UAS) allows a single operator to survey a waterbody more efficiently and rapidly, enhancing both coverage and data collection. Therefore, the objective of this research was to develop remote sensing techniques to assess herbicide efficacy for water hyacinth control in an outdoor mesocosm study. Experiments were conducted in spring and summer 2023 to compare and correlate data from visual evaluations of herbicide efficacy against nine vegetation indices (VIs) derived from UAS-based red-green-blue imagery. Penoxsulam, carfentrazone, diquat, 2,4-D, florpyrauxifen-benzyl, and glyphosate were applied at two rates, and experimental units were evaluated for 6 wk. The carotenoid reflectance index (CRI) had the highest Spearman’s correlation coefficient with visually evaluated efficacy for 2,4-D, diquat, and florpyrauxifen benzyl (> −0.77). The visible atmospherically resistance index (VARI) had the highest correlation with carfentrazone and penoxsulam treatments (> −0.70), and the excess greenness minus redness index had the highest correlation for glyphosate treatments (> −0.83). CRI had the highest correlation coefficient with the most herbicide treatments, and it was the only VI tested that did not include the red band. These VIs were satisfactory predictors of mid-range visually evaluated herbicide efficacy values but were poorly correlated with extremely low and high values, corresponding to nontreated and necrotic plants. Future research should focus on applying findings to real-world (nonexperimental) field conditions and testing imagery with spectral bands beyond the visible range.
The compromise effect arises when being close to the “middle” of a choice set makes an option more appealing. The compromise effect poses conceptual and practical problems for economic research: by influencing choices, it can bias researchers’ inferences about preference parameters. To study this bias, we conduct an experiment with 550 participants who made choices over lotteries from multiple price lists (MPLs). Following prior work, we manipulate the compromise effect to influence choices by varying the middle options of each MPL. We then estimate risk preferences using a discrete-choice model without a compromise effect embedded in the model. As anticipated, the resulting risk preference parameter estimates are not robust, changing as the compromise effect is manipulated. To disentangle risk preference parameters from the compromise effect and to measure the strength of the compromise effect, we augment our discrete-choice model with additional parameters that represent a rising penalty for expressing an indifference point further from the middle of the ordered MPL. Using this method, we estimate an economically significant magnitude for the compromise effect and generate robust estimates of risk preference parameters that are no longer sensitive to compromise-effect manipulations.
We report the case of a 16-year-old female with previously diagnosed bilateral sub-segmental pulmonary emboli who presented in cardiogenic shock from depressed biventricular function with cardiac MRI demonstrating concern for microvascular coronary injury. She was ultimately diagnosed with catastrophic antiphospholipid antibody syndrome-induced ischaemic cardiomyopathy, potentially associated with an underlying autoimmune connective tissue disease.
This study investigates the impact of coronavirus disease 2019 (COVID-19) pandemic on HTAsiaLink members at the organizational level and provides recommendations for mitigating similar challenges in the future.
Methods
A survey was disseminated among HTAsiaLink members to assess the COVID-19 impact in three areas: (i) inputs, (ii) process, and (iii) outputs of the Health Technology Assessment organizations’ (HTAOs) research operations and HTA process in general.
Results
Survey results showed that most HTAOs hired more staff and secured similar or higher funding levels during COVID-19. Nevertheless, some organizations reported high staff turnover. COVID-19-relevant research was prioritized, and most of the organizations had to adapt their research design to meet the needs of policymakers. Time constraints in conducting research and inability to collect primary data were reported as impacts on the research process. Overall, the number of research projects and accessibility of respondents’ publications increased during COVID-19.
Conclusions
Research demand for HTAOs increased during COVID-19 and impacted their research process; however, they demonstrated resilience and adaptability to provide timely evidence for policymakers. With the growing reliance on HTA, HTAOs require adequate financial support, continuous capacity building, collaboration, and partnership, innovative HTA methods, and a pragmatic yet robust, evidence-to-policy process in preparation for future pandemics.
Dementia is a common and progressive condition whose prevalence is growing worldwide. It is challenging for healthcare systems to provide continuity in clinical services for all patients from diagnosis to death.
Aims
To test whether individuals who are most likely to need enhanced care later in the disease course can be identified at the point of diagnosis, thus allowing the targeted intervention.
Method
We used clinical information collected routinely in de-identified electronic patient records from two UK National Health Service (NHS) trusts to identify at diagnosis which individuals were at increased risk of needing enhanced care (psychiatric in-patient or intensive (crisis) community care).
Results
We examined the records of a total of 25 326 patients with dementia. A minority (16% in the Cambridgeshire trust and 2.4% in the London trust) needed enhanced care. Patients who needed enhanced care differed from those who did not in age, cognitive test scores and Health of the Nation Outcome Scale scores. Logistic regression discriminated risk, with an area under the receiver operating characteristic curve (AUROC) of up to 0.78 after 1 year and 0.74 after 4 years. We were able to confirm the validity of the approach in two trusts that differed widely in the populations they serve.
Conclusions
It is possible to identify, at the time of diagnosis of dementia, individuals most likely to need enhanced care later in the disease course. This permits the development of targeted clinical interventions for this high-risk group.
Phase three trials of the monoclonal antibodies lecanemab and donanemab, which target brain amyloid, have reported statistically significant differences in clinical end-points in early Alzheimer's disease. These drugs are already in use in some countries and are going through the regulatory approval process for use in the UK. Concerns have been raised about the ability of healthcare systems, including those in the UK, to deliver these treatments, considering the resources required for their administration and monitoring.
Aims
To estimate the scale of real-world demand for monoclonal antibodies for Alzheimer's disease in the UK.
Method
We used anonymised patient record databases from two National Health Service trusts for the year 2019 to collect clinical, demographic, cognitive and neuroimaging data for these cohorts. Eligibility for treatment was assessed using the inclusion criteria from the clinical trials of donanemab and lecanemab, with consideration given to diagnosis, cognitive performance, cerebrovascular disease and willingness to receive treatment.
Results
We examined the records of 82 386 people referred to services covering around 2.2 million people. After applying the trial criteria, we estimate that a maximum of 906 people per year would start treatment with monoclonal antibodies in the two services, equating to 30 200 people if extrapolated nationally.
Conclusions
Monoclonal antibody treatments for Alzheimer's disease are likely to present a significant challenge for healthcare services to deliver in terms of the neuroimaging and treatment delivery. The data provided here allows health services to understand the potential demand and plan accordingly.
Diagnostic criteria for mild cognitive impairment (MCI) include a report of cognitive decline from the patient or a close informant. It is therefore important to understand the relationship between self- and informant-rated cognition and actual patient performance. Furthermore, it is unknown whether the nature of the relationship between the patient and their informant impacts accuracy of subjective reports. This study aimed to determine the association between informant report, self-report and objective cognitive performance based on relationship factors. We predicted that informant report would be more closely associated with objective performance than self-report after controlling for demographics and mood (Geriatric Depression Scale [mean= 1.4, SD=2]), especially among those who live with the participant and those who are spouses/partners.
Participants and Methods:
Participants (n = 338; age= 73.5 ±6.7) of varying diagnoses and their respective informants were drawn from the longitudinal cohort of the Michigan Alzheimer’s Disease Research Center (MADRC). The majority of informants were spouses/significant others (55.6%), followed by 23.7% being other family members and 20.7% were non- family members; 58.9% of informants live with the participant. Both respondents completed the Cognitive Change Index (CCI) to rate the patient’s cognitive status (higher scores indicating worsening cognition) across three domains: memory (12 questions), language (1 question), and attention/executive functioning (7 questions). These domains were matched to objective cognitive performance measured using the MADRC neuropsychological battery. Executive functioning and attention were assessed using Number Span Test Forward and Backward (NSF, NSB) and Trail Making Test Part B and Trail- Making Test Part A and B ratio (TMTB, TMTB: A); memory was measured using Craft Story 21 (Immediate and Delayed), Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall, Delayed Recall, and Benson Complex Figure (BCF) Delayed Recall; and Language was measured by the Controlled Oral Word Association Test (COWAT) and Animal fluency.
Results:
Linear regression adjusted for sex, race, and mood indicated that both patient and informant CCI ratings were significantly (p<.05) associated with objective cognitive performance. For every one unit increase on executive CCI items, there was a significant decline in executive functioning (NSF patient and informant ß= -0.09, NSB: [ßP= -.14; ßp-0.13]) and TMTB [ßP= 3.85; ß= 3.10 [% change]). Memory performance also declined per unit increase on CCI memory items: (Craft Story 21 Immediate [ßP=-0.32; ß= -0.37] and Delayed [ßP=-.40; ßp -.47], HVLT-R Total Recall [ßP= -.31; ßI=-.37] and Delayed Recall [ßP= -.16; ß=-.20], and BCF Delayed Recall [ßP= -.18; ß= -.23]. Similarly, one unit increase on the single CCI language item was associated with a decline in COWAT (ßP= -2.27; ß= -4.61) and Animal fluency (ßP= -1.88; ß= -3.03). Effect modification by participant-informant relationship type or participant-informant cohabitation was not significant.
Conclusions:
Patient and informant ratings are associated with objective measures of cognition regardless of the relationship between informant and patient or if they live together. This study was limited by a well-educated sample (mean= 16.1 years of education, SD= 2.4 years) with relatively limited diversity among participant-informant relationships. Future studies should replicate analyses across a larger and more diverse sample.
Telecommunication-assisted neuropsychological assessment (teleNP) has become more widespread, particularly in response to the COVID-19 pandemic. However, comparatively few studies have evaluated in-home teleNP testing and none, to our knowledge, have evaluated the National Alzheimer’s Coordinating Center’s (NACC) Uniform Data Set version 3 tele-adapted test battery (UDS v3.0 t-cog). The current study compares in-home teleNP administration of the UDS v3.0, acquired while in-person activities were suspended due to COVID-19, with a prior in-person UDS v3.0 evaluation.
Participants and Methods:
210 participants from the Michigan Alzheimer’s Disease Research Center’s longitudinal study of memory and aging completed both an in-person UDS v3.0 and a subsequent teleNP UDS v3.0 evaluation. The teleNP UDS v3.0 was administered either via video conference (n = 131), telephone (n = 75), or hybrid format (n = 4) with approximately 16 months between evaluations (mean = 484.7 days; SD = 122.4 days; range = 320-986 days). The following clinical phenotypes were represented at the initial assessment period (i.e., the most recent in-person UDS v3.0 evaluation prior to the teleNP UDS v3.0): cognitively healthy (n = 138), mild cognitive impairment (MCI; n = 60), dementia (n = 11), and impaired not MCI (n = 1). Tests included both the in-person and teleNP UDS v3.0 measures, as well as the Hopkins Verbal Learning Test-Revised (HVLT-R) and Letter “C” Fluency.
Results:
We calculated intraclass correlation coefficients (ICC) with raw scores from each time point for the entire sample. Sub-analyses were conducted for each phenotype among participants with an unchanged consensus research diagnosis: cognitively healthy (n = 122), MCI (n = 47), or cognitively impaired (i.e., MCI, dementia, and impaired not MCI) (n = 66). Test-retest reliability across modalities and clinical phenotypes was, in general, moderate. The poorest agreement was associated with the Trail Making Test (TMT) - A (ICC = 0.00; r = 0.027), TMT - B (ICC = 0.26; r = 0.44), and Number Span Backward (ICC = 0.49). The HVLT-R demonstrated moderate reliability overall (ICC = 0.51-0.68) but had notably weak reliability for cognitively healthy participants (ICC = 0.12-0.36). The most favorable reliability was observed in Craft Story 21 Recall - Delayed (ICC = 0.77), Letter Fluency (C, F, and L) (ICC = 0.74), Multilingual Naming Test (MINT) (ICC = 0.75), and Benson Complex Figure – Delayed (ICC = 0.79).
Conclusions:
Even after accounting for the inherent limitations of this study (e.g., significant lapse of time between testing intervals), our findings suggest that the UDS v3.0 teleNP battery shows only modest relationships with its in-person counterpart. Particular caution should be used when interpreting measures showing questionable reliability, though we encourage further investigation of remote vs. in-person testing under more controlled conditions.
In research, and particularly clinical trials, it is important to identify persons at high risk for developing Alzheimer’s Disease (AD), such as those with Mild Cognitive Impairment (MCI). However, not all persons with this diagnosis have a high risk of AD as MCI can be broken down further into amnestic MCI (aMCI), who have a high risk specifically for AD, and non-amnestic MCI (naMCI), who are predominantly at risk for other dementias. People with aMCI largely differ from healthy controls and naMCI on memory tasks as it is the hallmark criteria for an amnestic diagnosis. Given the growing use of the NIH Toolbox Cognition battery in research trials, this project investigated which Toolbox Cognition measures best differentiated aMCI from naMCI and in comparison to persons with normal cognition.
Participants and Methods:
A retrospective data analysis was conducted investigating performance on NIH Toolbox Cognition tasks among 199 participants enrolled in the Michigan Alzheimer’s Disease Research Center. All participants were over age 50 (51-89 years, M=70.64) and had a diagnosis of aMCI (N=74), naMCI (N=24), or Normal Cognition (N=101). Potential demographic differences were investigated using chi-square and ANOVAs. Repeated measure general linear model was used to look at potential group differences in Toolbox Cognition performance, covarying for age which was statistically different in aMCI versus Normal participants. Linear regression was used to determine which cognitive abilities, as measured by the Uniform Data Set-3 (UDS3), might contribute to Toolbox differences noted in naMCI versus aMCI groups.
Results:
As expected, aMCI had lower Toolbox memory scores compared to naMCI (p=0.007) and Normals (p<0.001). Interestingly, naMCI had lower Oral Reading scores than both aMCI (p=0.008) and Normals (p<0.001). There were no other Toolbox performance differences between the MCI groups. 19.4% of the variance in Oral Reading scores was explained by performance on the following UDS3 measures: Benson delayed recall (inverse relationship) and backward digit span and phonemic fluency (positive relationship).
Conclusions:
In this study, Toolbox Picture Sequence Memory and Oral Reading scores differentiated aMCI and naMCI groups. While the difference in memory was expected, it was surprising that the naMCI group performed worse than the aMCI and normal groups on the Toolbox Oral Reading task, a task presumed to reflect Crystalized abilities resistive to cognitive decline. Results suggest that Oral Reading is primarily positively associated with working memory and executive tasks from the UDS3, but negatively associated with visual memory. It is possible that the Oral Reading subtest is sensitive to domains of deficit aside from memory that can best distinguish aMCI from naMCI. A better understanding of the underlying features in the Oral Reading task will assist in better characterizing deficit patterns seen in naMCI, making selection of aMCI participants more effective in clinical trials.
The Jostedalsbreen ice cap is mainland Europe's largest ice cap and accommodates 20% (458 km2 in 2019) of the total glacier area of mainland Norway. Jostedalsbreen and its meltwater contribute to global sea-level rise and to local water management, hydropower and tourism economies and livelihoods. In this study, we construct a digital terrain model (DTM) of the ice cap from 1966 aerial photographs, which by comparing to an airborne LiDAR DTM from 2020, we compute changes in surface elevation and geodetic mass balances. The area mapped in both surveys cover about 3/4 of the ice cap area and 49 of 82 glaciers. The measured glacier area has decreased from 363.4 km2 in 1966 to 332.9 km2 in 2019, i.e. a change of −30 km2 or −8.4% (−0.16% a−1), which is in line with the percentage reduction in area for Jostedalsbreen as a whole. The mean geodetic mass balance over the 49 glaciers was −0.15 ± 0.01 m w.e. a−1, however, large variability is evident between glaciers, e.g. Nigardsbreen (−0.05 m w.e. a−1), Austdalsbreen (−0.28 m w.e. a−1) and Tunsbergdalsbreen (−0.36 m w.e. a−1) confirming differences also found by the glaciological records for Nigardsbreen and Austdalsbreen.
We report a case of hypoplastic left heart syndrome and with subsequent aortopathy and then found to have hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome due to a germline SMAD4 pathologic variant. The patient’s staged palliation was complicated by the development of neoaortic aneurysms, arteriovenous malformations, and gastrointestinal bleeding thought to be secondary to Fontan circulation, but workup revealed a SMAD4 variant consistent with hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome. This case underscores the importance of genetic modifiers in CHD, especially those with Fontan physiology.
Few studies have evaluated in-home teleneuropsychological (teleNP) assessment and none, to our knowledge, has evaluated the National Alzheimer’s Coordinating Center’s (NACC) Uniform Data Set version 3 tele-adapted test battery (UDS v3.0 t-cog). The current study evaluates the reliability of the in-home UDS v3.0 t-cog with a prior in-person UDS v3.0 evaluation.
Method:
One hundred and eighty-one cognitively unimpaired or cognitively impaired participants from a longitudinal study of memory and aging completed an in-person UDS v3.0 and a subsequent UDS v3.0 t-cog evaluation (∼16 months apart) administered either via video conference (n = 122) or telephone (n = 59).
Results:
We calculated intraclass correlation coefficients (ICCs) between each time point for the entire sample. ICCs ranged widely (0.01–0.79) but were generally indicative of “moderate” (i.e., ICCs ranging from 0.5–0.75) to “good” (i.e., ICCs ranging from 0.75–0.90) agreement. Comparable ICCs were evident when looking only at those with stable diagnoses. However, relatively stronger ICCs (Range: 0.35–0.87) were found between similarly timed in-person UDS v3.0 evaluations.
Conclusions:
Our findings suggest that most tests on the UDS v3.0 t-cog battery may serve as a viable alternative to its in-person counterpart, though reliability may be attenuated relative to the traditional in-person format. More tightly controlled studies are needed to better establish the reliability of these measures.
Psychological and cultural evolutionary accounts of human sociality propose that beliefs in punitive and monitoring gods that care about moral norms facilitate cooperation. While there is some evidence to suggest that belief in supernatural punishment and monitoring generally induce cooperative behaviour, the effect of a deity's explicitly postulated moral concerns on cooperation remains unclear. Here, we report a pre-registered set of analyses to assess whether perceiving a locally relevant deity as moralistic predicts cooperative play in two permutations of two economic games using data from up to 15 diverse field sites. Across games, results suggest that gods’ moral concerns do not play a direct, cross-culturally reliable role in motivating cooperative behaviour. The study contributes substantially to the current literature by testing a central hypothesis in the evolutionary and cognitive science of religion with a large and culturally diverse dataset using behavioural and ethnographically rich methods.
OBJECTIVES/GOALS: Our overall objective is to investigate the relationship between radiologic features of meningioma with recently identified histopathological and molecular biomarkers, and to apply a machine learning (ML) approach to further demonstrate their utility in predicting clinical outcomes. METHODS/STUDY POPULATION: We have enrolled a cohort of 84 patients with meningioma diagnosed on the basis of conventional gadolinium-enhanced MRI imaging features since September 2019. Each patient has demographic and clinical data, Ga-68-DOTATATE MRI/PET SUV and dynamic metrics, DCE-MRI perfusion parameters, and histopathologic data. Various tumor subregions will be segmented semi-automatically and later confirmed by experienced neuroradiologist. Histopathologic data will include histologic grade, mitotic rate, Ki67 proliferative index, and presence of WHO established atypical histologic features, immunohistochemical parameters, and established high-grade molecular features. We will use supervised learning techniques to develop algorithms for predicting molecular features from imaging phenotypes. RESULTS/ANTICIPATED RESULTS: Anticipated results - advancements in understanding the molecular biomarkers of meningiomas has uncovered genetic alterations and epigenetic changes that more accurately determine tumor behavior. Currently, the imaging correlates of these molecular biomarkers are unknown, and utilizing radiographic data to predict prognosis and imaging-based classifications of meningiomas have not yet been investigated. Validated imaging correlates of molecular biomarkers not only provide an in-vivo assessment of tumor biology, but can also be integrated with histopathologic features ( radiopathomics models’) for more accurate disease prognostication. We anticipate that our results will identify surrogate imaging features for some of the recently emerged molecular biomarkers of meningioma. DISCUSSION/SIGNIFICANCE: There is a paucity of data on the importance of imaging phenotypes in determining tumor biology. This work has the potential of significant clinical impact by enabling a priori molecular characterization of meningiomas at the time of new diagnosis or recurrence, thereby allowing a personalized medicine approach to treatment planning.
OBJECTIVES/GOALS: Current COVID-19 rapid molecular tests require cartridge-reader detection, expensive circuitry, and complex microfluidics making the most accurate tests unavailable to the masses. Here we present a rapid molecular diagnostic leveraging isothermal amplification and paper-based microfluidics for a low-cost ultra-sensitive COVID-19 assay. METHODS/STUDY POPULATION: We designed a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of SARS-CoV-2 and bacteriophage MS2 RNA. RT-RPA is a sequence specific, ultrasensitive, rapid isothermal DNA amplification technique that is well suited to home based testing due to its rapid assay time, robustness, ease of use, and readout options. RT-RPA reagents are added to a tube and incubated at 39°C in a fluorometer. Realtime fluorometer data gives results in under 15 minutes. This assay also provides visual detection via lateral flow readout with results in 23 minutes. RESULTS/ANTICIPATED RESULTS: We have developed a rapid multiplexed nucleic acid amplification assay with an internal process control for SARS-CoV-2 using single-pot RT-RPA. We screened 21 primer combinations to select primers that demonstrated excellent performance and target specificity against common respiratory viruses. We demonstrate the ability to multiplex SARS-CoV-2 and MS2 detection, utilizing MS2 as an internal process control for lysis, reverse transcription, amplification, and readout. We show duplexed detection using both fluorescence readout and visual readout using lateral flow strips. Duplexed fluorescence detection shows a limit of detection of 25 copies per reaction. Duplexed lateral flow readout shows a limit of detection of 50 copies per reaction DISCUSSION/SIGNIFICANCE: We developed a duplexed RT-RPA assay for SARS-CoV-2 with fluorescence or lateral flow readout. Our assay does not re-quire expensive reader, circuity, or fluid handling. The low material cost, temperature, and robustness make it ideal for a more accurate home-based COVID-19 diagnostic.
The Horus and other research teams have found that atherosclerosis is not uncommon in ancient people through the study of their mummified remains (Murphy et al., 2003; Allam et al., 2009, 2011; Thompson et al., 2013, 2014). However, some have postulated that traditional hunter-gatherers are in some ways healthier than modern people and that they had very little atherosclerotic disease (O’Keefe et al., 2010).
Annual seasonal influenza vaccination is recommended for individuals at high risk of developing post-infection complications in many locations. However, reduced vaccine immunogenicity and effectiveness have been observed among repeat vaccinees in some influenza seasons. We investigated the impact of repeated influenza vaccination on relative vaccine effectiveness (VE) among individuals who were recommended for influenza vaccination in the United Kingdom with a retrospective cohort study using primary healthcare data from the Clinical Practice Research Datalink, a primary care database in the United Kingdom. Relative VE was estimated against general practitioner-diagnosed influenza-like illnesses (GP-ILI) and medically attended acute respiratory illnesses (MAARI) among participants who have been repeatedly vaccinated compared with first-time vaccinees using proportional hazards models. Relative VE against MAARI may be reduced for individuals above 65 years old who were vaccinated in the current and previous influenza seasons for some influenza seasons. However, these findings were not conclusive as we could not exclude the possibility of residual confounding in our dataset. The use of routinely collected data from electronic health records to examine the effects of repeated vaccination needs to be complemented with sufficient efforts to include negative control outcomes to rule out residual confounding.