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The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort study of the Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to catalyze research on dementia, set up to support the research agendas of CCNA teams. This cross-country longitudinal cohort of 2310 deeply phenotyped subjects with various forms of dementia and mild memory loss or concerns, along with cognitively intact elderly subjects, will test hypotheses generated by these teams.
The COMPASS-ND protocol, initial grant proposal for funding, fifth semi-annual CCNA Progress Report submitted to the Canadian Institutes of Health Research December 2017, and other documents supplemented by modifications made and lessons learned after implementation were used by the authors to create the description of the study provided here.
The CCNA COMPASS-ND cohort includes participants from across Canada with various cognitive conditions associated with or at risk of neurodegenerative diseases. They will undergo a wide range of experimental, clinical, imaging, and genetic investigation to specifically address the causes, diagnosis, treatment, and prevention of these conditions in the aging population. Data derived from clinical and cognitive assessments, biospecimens, brain imaging, genetics, and brain donations will be used to test hypotheses generated by CCNA research teams and other Canadian researchers. The study is the most comprehensive and ambitious Canadian study of dementia. Initial data posting occurred in 2018, with the full cohort to be accrued by 2020.
Availability of data from the COMPASS-ND study will provide a major stimulus for dementia research in Canada in the coming years.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
Laboratory identification of carbapenem-resistant Enterobacteriaceae (CRE) is a key step in controlling its spread. Our survey showed that most Veterans Affairs laboratories follow VA guidelines for initial CRE identification, whereas 55.0% use PCR to confirm carbapenemase production. Most respondents were knowledgeable about CRE guidelines. Barriers included staffing, training, and financial resources.
Although most hospitals report very high levels of hand hygiene compliance (HHC), the accuracy of these overtly observed rates is questionable due to the Hawthorne effect and other sources of bias. In the study, we aimed (1) to compare HHC rates estimated using the standard audit method of overt observation by a known observer and a new audit method that employed a rapid (<15 minutes) “secret shopper” method and (2) to pilot test a novel feedback tool.
Quality improvement project using a quasi-experimental stepped-wedge design.
This study was conducted in 5 acute-care hospitals (17 wards, 5 intensive care units) in the Midwestern United States.
Sites recruited a hand hygiene observer from outside the acute-care units to rapidly and covertly observe entry and exit HHC during the study period, October 2016–September 2017. After 3 months of observations, sites received a monthly feedback tool that communicated HHC information from the new audit method.
The absolute difference in HHC estimates between the standard and new audit methods was ~30%. No significant differences in HHC were detected between the baseline and feedback phases (OR, 0.92; 95% CI, 0.84–1.01), but the standard audit method had significantly higher estimates than the new audit method (OR, 9.83; 95% CI, 8.82–10.95).
HHC estimates obtained using the new audit method were substantially lower than estimates obtained using the standard audit method, suggesting that the rapid, secret-shopper method is less subject to bias. Providing feedback using HHC from the new audit method did not seem to impact HHC behaviors.
Important Bird and Biodiversity Areas (IBAs) are sites identified as being globally important for the conservation of bird populations on the basis of an internationally agreed set of criteria. We present the first review of the development and spread of the IBA concept since it was launched by BirdLife International (then ICBP) in 1979 and examine some of the characteristics of the resulting inventory. Over 13,000 global and regional IBAs have so far been identified and documented in terrestrial, freshwater and marine ecosystems in almost all of the world’s countries and territories, making this the largest global network of sites of significance for biodiversity. IBAs have been identified using standardised, data-driven criteria that have been developed and applied at global and regional levels. These criteria capture multiple dimensions of a site’s significance for avian biodiversity and relate to populations of globally threatened species (68.6% of the 10,746 IBAs that meet global criteria), restricted-range species (25.4%), biome-restricted species (27.5%) and congregatory species (50.3%); many global IBAs (52.7%) trigger two or more of these criteria. IBAs range in size from < 1 km2 to over 300,000 km2 and have an approximately log-normal size distribution (median = 125.0 km2, mean = 1,202.6 km2). They cover approximately 6.7% of the terrestrial, 1.6% of the marine and 3.1% of the total surface area of the Earth. The launch in 2016 of the KBA Global Standard, which aims to identify, document and conserve sites that contribute to the global persistence of wider biodiversity, and whose criteria for site identification build on those developed for IBAs, is a logical evolution of the IBA concept. The role of IBAs in conservation planning, policy and practice is reviewed elsewhere. Future technical priorities for the IBA initiative include completion of the global inventory, particularly in the marine environment, keeping the dataset up to date, and improving the systematic monitoring of these sites.
OBJECTIVES/SPECIFIC AIMS: The purpose of the present secondary data analysis was to examine the effect of moderate-severe disturbed sleep before the start of radiation therapy (RT) on subsequent RT-induced pain. METHODS/STUDY POPULATION: Analyses were performed on 676 RT-naïve breast cancer patients (mean age 58, 100% female) scheduled to receive RT from a previously completed nationwide, multicenter, phase II randomized controlled trial examining the efficacy of oral curcumin on radiation dermatitis severity. The trial was conducted at 21 community oncology practices throughout the US affiliated with the University of Rochester Cancer Center NCI’s Community Oncology Research Program (URCC NCORP) Research Base. Sleep disturbance was assessed using a single item question from the modified MD Anderson Symptom Inventory (SI) on a 0–10 scale, with higher scores indicating greater sleep disturbance. Total subjective pain as well as the subdomains of pain (sensory, affective, and perceived) were assessed by the short-form McGill Pain Questionnaire. Pain at treatment site (pain-Tx) was also assessed using a single item question from the SI. These assessments were included for pre-RT (baseline) and post-RT. For the present analyses, patients were dichotomized into 2 groups: those who had moderate-severe disturbed sleep at baseline (score≥4 on the SI; n=101) Versus those who had mild or no disturbed sleep (control group; score=0–3 on the SI; n=575). RESULTS/ANTICIPATED RESULTS: Prior to the start of RT, breast cancer patients with moderate-severe disturbed sleep at baseline were younger, less likely to have had lumpectomy or partial mastectomy while more likely to have had total mastectomy and chemotherapy, more likely to be on sleep, anti-anxiety/depression, and prescription pain medications, and more likely to suffer from depression or anxiety disorder than the control group (all p’s≤0.02). Spearman rank correlations showed that changes in sleep disturbance from baseline to post-RT were significantly correlated with concurrent changes in total pain (r=0.38; p<0.001), sensory pain (r=0.35; p<0.001), affective pain (r=0.21; p<0.001), perceived pain intensity (r=0.37; p<0.001), and pain-Tx (r=0.35; p<0.001). In total, 92% of patients with moderate-severe disturbed sleep at baseline reported post-RT total pain compared with 79% of patients in the control group (p=0.006). Generalized linear estimating equations, after controlling for baseline pain and other covariates (baseline fatigue and distress, age, sleep medications, anti-anxiety/depression medications, prescription pain medications, and depression or anxiety disorder), showed that patients with moderate-severe disturbed sleep at baseline had significantly higher mean values of post-RT total pain (by 39%; p=0.033), post-RT sensory pain (by 41%; p=0.046), and post-RT affective pain (by 55%; p=0.035) than the control group. Perceived pain intensity (p=0.066) and pain-Tx (p=0.086) at post-RT were not significantly different between the 2 groups. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that moderate-severe disturbed sleep prior to RT is an important predictor for worsening of pain at post-RT in breast cancer patients. There could be several plausible reasons for this. Sleep disturbance, such as sleep loss and sleep continuity disturbance, could result in impaired sleep related recovery and repair of tissue damage associated with cancer and its treatment; thus, resulting in the amplification of pain. Sleep disturbance may also reduce pain tolerance threshold through increased sensitization of the central nervous system. In addition, pain and sleep disturbance may share common neuroimmunological pathways. Sleep disturbance may modulate inflammation, which in turn may contribute to increased pain. Further research is needed to confirm these findings and whether interventions targeting sleep disturbance in early phase could be potential alternate approaches to reduce pain after RT.
OBJECTIVES/SPECIFIC AIMS: The goal of the present study was to advance our understanding of how alcohol use may contribute to physical inactivity among university students by investigating this association at a day-to-day level. METHODS/STUDY POPULATION: In total, 57 university students (Mage=20.27; 54% male) completed daily diary questionnaires using a cellphone application, which prompted them each evening to report minutes of moderate/vigorous physical activity engaged in, and number of alcoholic drinks consumed, as well as intended minutes of physical activity for the following day. Longitudinal mixed-level modeling was used to disentangle within person and between-person effects of alcohol use on physical activity behavior and intentions. Separate models were run to investigate lagged effects of previous day alcohol use. We controlled for sex and age in all models. RESULTS/ANTICIPATED RESULTS: Results indicated that participants’ usual alcohol use (between-person) was not associated with physical activity behavior or intentions. At the within-person level, day-to-day variance in alcohol use was negatively associated with both physical activity behavior (γ=−0.34, p=0.003) and intentions to engage in physical activity the following day (γ=−0.70, p<0.001). The lagged model indicated that previous day alcohol use negatively predicted PA behavior (γ=−0.33, p=0.004). DISCUSSION/SIGNIFICANCE OF IMPACT: Previous studies have largely been constrained to cross-sectional designs, and have surmised that there exists a positive association between alcohol use and physical activity due to trait-level differences between university students. We advance this literature by using ecological momentary assessment to investigate the within-person effects of alcohol use on physical activity at a day-to-day level while controlling for between-person variance. Contrary to existing literature, we found that on days when students consumed relatively more alcohol than they typically report, they: (a) report fewer minutes of physical activity on the same day, (b) plan to engage in relatively less physical activity on the subsequent day, and (c) engage in less physical activity on the subsequent day. By advancing our understanding of how alcohol use may curtail other health behaviors such as physical activity, we inform interventions that aim to target these behaviors in conjunction, or as part of a multiple behavior change intervention.
This paper explores what motivates improved health care performance. Previously, many have thought that performance would either improve via choice and competition or by relying on trust and altruism. But neither assumption is supported by available evidence. So instead we explore a third approach of reciprocal altruism with sanctions for unacceptably poor performance and rewards for high performance. These rewards and sanctions, however, are not monetary, but in the form of reputational effects through public reporting of benchmarking of performance. Drawing on natural experiments in Italy and the United Kingdom, we illustrate how public benchmarking can improve poor performance at the national level through ‘naming and shaming’ and enhance good performance at the sub-national level through ‘competitive benchmarking’ and peer learning. Ethnographic research in Zambia also showed how reputations count. Policy-makers could use these effects in different ways to improve public services.
Posthodiplostomum minimum utilizes a three-host life cycle with multiple developmental stages. The metacercarial stage, commonly known as ‘white grub’, infects the visceral organs of many freshwater fishes and was historically considered a host generalist due to its limited morphological variation among a wide range of hosts. In this study, infection data and molecular techniques were used to evaluate the host and tissue specificity of Posthodiplostomum metacercariae in centrarchid fishes. Eleven centrarchid species from three genera were collected from the Illinois portion of the Ohio River drainage and necropsied. Posthodiplostomum infection levels differed significantly by host age, host genera and infection locality. Three Posthodiplostomum spp. were identified by DNA sequencing, two of which were relatively common within centrarchid hosts. Both common species were host specialists at the genus level, with one species restricted to Micropterus hosts and the other preferentially infecting Lepomis. Host specificity is likely dictated by physiological compatibility and deviations from Lepomis host specificity may be related to host hybridization. Posthodiplostomum species also differed in their utilization of host tissues. Neither common species displayed strong genetic structure over the scale of this study, likely due to their utilization of bird definitive hosts.
Militant groups, like all organizations, carefully consider the tactics and strategies that they employ. We assess why some militant organizations diversify into multiple tactics while others limit themselves to just one or a few. This is an important puzzle because militant organizations that employ multiple approaches to violence are more likely to stretch state defenses, achieve tactical success, and threaten state security. We theorize that militant organizations respond to external pressure by diversifying their tactics to ensure their survival and continued relevance, and that the primary sources of such pressure are government repression and interorganizational competition. We find consistent support for these propositions in tests of both the Global Terrorism Database (GTD) and Minorities at Risk Organizational Behavior (MAROB) data sets. We bolster these findings with an additional specification that employs ethnic fractionalization in the first stage of a multi-process recursive model. These findings are relevant not only for academic research but for policy as well. While it is difficult for countries to anticipate the character of future tactical choices, they may be able to anticipate which groups will most readily diversify and thereby complicate counterterrorism efforts.
Medusaceratops lokii Ryan, Russell, and Hartman, 2010 is an enigmatic taxon of ceratopsid represented by partial parietals from the Mansfield bonebed in the Campanian Judith River Formation, Montana. Originally, all ceratopsid material collected from this bonebed was referred to the centrosaurine ceratopsid Albertaceratops, but subsequently two parietals were designated the types of the chasmosaurine, M. lokii, in part, because they were interpreted to have three epiparietals bilaterally. Here we describe new material from the bonebed that allows a systematic revision of the taxon. A revised reconstruction of the frill, informed by newly discovered parietals, reveals that M. lokii had a broad midline ramus and at least five epiparietals (ep) around the margin of the frill, both traits that are characteristic of Centrosaurinae. From medial to lateral, the epiparietal ornamentation consists of a small, variably procurving epiparietal (ep 1), an anterolaterally curving pachyostotic hook (ep 2), a smaller pachyostoic process (ep 3), and two small triangular epiparietals (ep 4 and 5). A phylogenetic analysis of ceratopsids, which is the first to include Medusaceratops, indicates that M. lokii is a unique, early centrosaurine ceratopsid taxon that is more closely related to Centrosaurini and Pachyrhinosaurini than Nasutoceratopsini. No unequivocal chasmosaurine bones or diagnostic material from any other ceratopsid could be identified from the Mansfield bonebed, suggesting that it represents one of the oldest occurrences of a monodominant accumulation of a centrosaurine ceratopsid on record.
To determine the impact of recurrent Clostridium difficile infection (RCDI) on patient behaviors following illness.
Using a computer algorithm, we searched the electronic medical records of 7 Chicago-area hospitals to identify patients with RCDI (2 episodes of CDI within 15 to 56 days of each other). RCDI was validated by medical record review. Patients were asked to complete a telephone survey. The survey included questions regarding general health, social isolation, symptom severity, emotional distress, and prevention behaviors.
In total, 119 patients completed the survey (32%). On average, respondents were 57.4 years old (standard deviation, 16.8); 57% were white, and ~50% reported hospitalization for CDI. At the time of their most recent illness, patients rated their diarrhea as high severity (58.5%) and their exhaustion as extreme (30.7%). Respondents indicated that they were very worried about getting sick again (41.5%) and about infecting others (31%). Almost 50% said that they have washed their hands more frequently (47%) and have increased their use of soap and water (45%) since their illness. Some of these patients (22%–32%) reported eating out less, avoiding certain medications and public areas, and increasing probiotic use. Most behavioral changes were unrelated to disease severity.
Having had RCDI appears to increase prevention-related behaviors in some patients. While some behaviors are appropriate (eg, handwashing), others are not supported by evidence of decreased risk and may negatively impact patient quality of life. Providers should discuss appropriate prevention behaviors with their patients and should clarify that other behaviors (eg, eating out less) will not affect their risk of future illness.
OBJECTIVES/SPECIFIC AIMS: Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of ~16 months. Novel methods to improve local control are needed. Nab-paclitaxel (abraxane) has shown efficacy in pancreatic cancer and is FDA approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced disease. METHODS/STUDY POPULATION: We performed a phase 1 study using a 3+3 dose-escalation strategy to determine the safety and tolerability of dose escalated nab-paclitaxel with fractionated radiotherapy for patients with unresectable or borderline resectable pancreatic cancer. Following induction chemotherapy with 2 cycles of nab-paclitaxel and gemcitabine, patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was performed at day 65 after the start of radiotherapy. RESULTS/ANTICIPATED RESULTS: Nine patients received nab-paclitaxel at a dose level of either 100 mg/m2 (n=3) or 125 mg/m2 (n=6). One DLT (grade 3 neuropathy) was observed in a patient who received 125 mg/m2 of nab-paclitaxel. Other grade 3 toxicities included fatigue (11%), anemia (11%), and neutropenia (11%). No grade 4 toxicities were observed. With a median follow-up of 8 months (range 5–28 months), median survival was 19 months and median progression-free survival was 10 months. Following chemoradiation, 3 patients underwent surgical resection, all with negative margins and limited tumor viability. Of the 3 patients, 2 initially had borderline resectable tumors and 1 had an unresectable tumor. Tumor (SMAD-4, Caveolin-1) and peripheral (circulating tumor cells and microvesicles) biomarkers were collected and are being analyzed. DISCUSSION/SIGNIFICANCE OF IMPACT: The combination of fractionated radiation and weekly nab-paclitaxel was safe and well tolerated. This regimen represents a potentially promising therapy for patients with unresectable and borderline resectable pancreatic cancer and warrants further investigation.
In the relatively gas-rich, pure exponential disk galaxies, available data is accumulating which suggests that the distribution of starformation in the disk either shows no radial variation, or else has a scale-length which is much longer than that of the stars.
After the Portuguese discovered the Cape Verde Islands in AD 1456 they divided its main island, Santiago, into two governing captaincies. The founding settlement in the south-west, Cidade Velha, soon became the Islands’ capital and a thriving trade centre; in contrast, that in the east, Alcatrazes, only lasted as an official seat from 1484–1516 and is held to have ‘failed’ (see Richter 2015).
Gaia DR1 was released in September 2016 and contained a photometric catalogue of over 1 billion sources. At this stage, this only included mean G-band photometry and an estimate of the error. Even though this may sound limited in nature, interesting science can still be achieved with this data thanks to its quality. A high level overview of the photometric processing and some validation results will be presented. Additionally, epoch photometry in the G-band was released in Gaia DR1 for a small number of variable sources in the South Ecliptic Pole which covers the LMC. The second data release (Gaia DR2) is currently being prepared and, if available, some preliminary validation results will be presented. It is planned that this release will contain colour information in the form of integrated BP and RP photometry in addition to the latest G-band photometry.
Major depressive disorder (MDD) is a leading cause of disability worldwide.
To examine the: (a) 12-month prevalence of DSM-IV MDD; (b) proportion aware that they have a problem needing treatment and who want care; (c) proportion of the latter receiving treatment; and (d) proportion of such treatment meeting minimal standards.
Representative community household surveys from 21 countries as part of the World Health Organization World Mental Health Surveys.
Of 51 547 respondents, 4.6% met 12-month criteria for DSM-IV MDD and of these 56.7% reported needing treatment. Among those who recognised their need for treatment, most (71.1%) made at least one visit to a service provider. Among those who received treatment, only 41.0% received treatment that met minimal standards. This resulted in only 16.5% of all individuals with 12-month MDD receiving minimally adequate treatment.
Only a minority of participants with MDD received minimally adequate treatment: 1 in 5 people in high-income and 1 in 27 in low-/lower-middle-income countries. Scaling up care for MDD requires fundamental transformations in community education and outreach, supply of treatment and quality of services.
We analyzed glacier surface elevations (1957, 2010 and 2015) and surface mass-balance measurements (2008–2015) on the 30 km2 Eklutna Glacier, in the Chugach Mountains of southcentral Alaska. The geodetic mass balances from 1957 to 2010 and 2010 to 2015 are −0.52 ± 0.46 and −0.74 ± 0.10 m w.e. a−1, respectively. The glaciological mass balance of −0.73 m w.e. a−1 from 2010 to 2015 is indistinguishable from the geodetic value. Even after accounting for loss of firn in the accumulation zone, we found most of the mass loss over both time periods was from a broad, low-slope basin that includes much of the accumulation zone of the main branch. Ice-equivalent surface elevation changes in the basin were −1.0 ± 0.8 m a−1 from 1957 to 2010, and −0.6 ± 0.1 m a−1 from 2010 to 2015, shifting the glacier hypsometry downward and resulting in more negative mass balances: an altitude-mass-balance feedback. Net mass loss from Eklutna Glacier accounts for 7 ± 1% of the average inflow to Eklutna Reservoir, which is entirely used for water and power by Anchorage, Alaska's largest city. If the altitude-mass-balance feedback continues, this ‘deglaciation discharge dividend’ is likely to increase over the short-term before it eventually decreases due to diminishing glacier area.