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OBJECTIVES/GOALS: Asthma is a significant health concern that affects people of all ages worldwide. EAS demonstrates many of the pathophysiological characteristics of nonatopic human asthma, which has led EAS to be used as naturally occurring model. Previous work from our lab determined that MARCKS (Myristoylated Alanine Rich C Kinase Substrate) protein is an essential regulator of cellular inflammatory functions. In the current study, we hypothesized that MARCKS levels would be increased in BAL cell lysates from horses with EAS, and that inhibition of MARCKS in zymosan-stimulated BAL cells (ex vivo) would diminish respiratory burst. METHODS/STUDY POPULATION: Lysates were prepared from BAL cells isolated from horses with no, mild/moderate and severe EAS. Relative MARCKS protein levels were determined using equine specific MARCKS ELISA (MyBioSource). Cultured BAL cells were pretreated with a MARCKS inhibitor peptide (MANS), control peptide (RNS) or vehicle control and stimulated with zymosan for 5 hours. Reactive oxygen species levels were determined by luminescence to evaluate respiratory burst. Data were analyzed by One-way ANOVA (p<0.05). RESULTS/ANTICIPATED RESULTS: We determined that normalized MARCKS protein expression is significantly increased in BAL cell lysates from horses with mild/moderate or severe EAS, compared to horses with normal BAL cytology. Preliminary findings also suggest that MANS treatment of zymosan-stimulated equine BAL cells ex vivo attenuates levels respiratory burst. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings point to a possible role for MARCKS protein in the pathophysiology of EAS and support MARCKS inhibition as a potential therapeutic strategy.
Healthcare personnel (HCP) were recruited to provide serum samples, which were tested for antibodies against Ebola or Lassa virus to evaluate for asymptomatic seroconversion.
From 2014 to 2016, 4 patients with Ebola virus disease (EVD) and 1 patient with Lassa fever (LF) were treated in the Serious Communicable Diseases Unit (SCDU) at Emory University Hospital. Strict infection control and clinical biosafety practices were implemented to prevent nosocomial transmission of EVD or LF to HCP.
All personnel who entered the SCDU who were required to measure their temperatures and complete a symptom questionnaire twice daily were eligible.
No employee developed symptomatic EVD or LF. EVD and LF antibody studies were performed on sera samples from 42 HCP. The 6 participants who had received investigational vaccination with a chimpanzee adenovirus type 3 vectored Ebola glycoprotein vaccine had high antibody titers to Ebola glycoprotein, but none had a response to Ebola nucleoprotein or VP40, or a response to LF antigens.
Patients infected with filoviruses and arenaviruses can be managed successfully without causing occupation-related symptomatic or asymptomatic infections. Meticulous attention to infection control and clinical biosafety practices by highly motivated, trained staff is critical to the safe care of patients with an infection from a special pathogen.
The Arizona Twin Project is an ongoing longitudinal study designed to elucidate gene–environment interplay underlying the development of risk and resilience to common mental and physical health problems during infancy, childhood and adolescence. Specificity of risk is carefully examined across mental and physical health and how these influences vary across socioeconomic and sociocultural environments. Participants are a sample of approximately 700 twins (31% Latinx) recruited from birth records in the state of Arizona, USA. Twins are 32% monozygotic twins, 36% same-sex dizygotic (DZ), 32% opposite-sex DZ, currently 10–11 years of age. Primary caregivers were interviewed on twins’ development and early physical and social environments when twins were 1, 2 and 5 years of age. In-depth objective measurement commenced in middle childhood, with in-person assessments at 8–11 years of age, with plans to continue to follow the sample across adolescence. Middle childhood measures focus on children’s physical and mental health, including diurnal cortisol, actigraphy-based measures of sleep and activity, cold pressor task assessing acute pain, and reaction time tasks assessing executive functioning. Preliminary findings illustrate that objective assessments of children’s health are highly heritable, but they do not always share genetic etiology with more commonly used subjective assessments. Exposure to early adversity moderates genetic influences on both executive functioning and health, with higher heritability typically seen under adverse conditions. Future directions include an examination of how pubertal stage affects genetic and environmental influences on diurnal cortisol, sleep, chronic pain, and mental health.
The recent discovery of a Late/Final Pre-Pottery Neolithic B burial of an adult and two children associated with fox bones at the site of Motza, Israel, demonstrates the broader socio-cultural perspective, and possibly continued animistic world views, of Neolithic foragers at the onset of the agricultural revolution.
This review aims to assess the cost-effectiveness of psychological interventions for schizophrenia/bipolar disorder (BD), to determine the robustness of current evidence and identify gaps in the available evidence.
Electronic searches (PsycINFO, MEDLINE, Embase) identified economic evaluations relating incremental cost to outcomes in the form of an incremental cost-effectiveness ratio published in English since 2000. Searches were concluded in November 2018. Inclusion criteria were: adults with schizophrenia/BD; any psychological/psychosocial intervention (e.g., psychological therapy and integrated/collaborative care); probability of cost-effectiveness at explicitly defined thresholds reported. Comparators could be routine practice, no intervention, or alternative psychological therapies. Screening, data extraction, and critical appraisal were performed using pre-specified criteria and forms. Results were summarized qualitatively. The protocol was registered on the PROSPERO database (CRD42017056579).
Of 3,864 studies identified, 12 met the criteria for data extraction. All were integrated clinical and economic randomized controlled trials. The most common intervention was cognitive behavioral therapy (CBT, 6/12 studies). The most common measure of health benefit was the quality-adjusted life-year (6/12). Follow-up ranged from 6 months to 5 years. Interventions were found to be cost-effective in most studies (9/12): the probability of cost-effectiveness ranged from 35-99.5 percent. All studies had limitations and demonstrated uncertainty (particularly related to incremental costs).
Most studies concluded psychological interventions for schizophrenia/BD are cost-effective, including CBT, although there was notable uncertainty. Heterogeneity across studies makes it difficult to reach strong conclusions. There is a particular need for more evidence in the population with BD and for longer-term evidence across both populations.
OBJECTIVES/SPECIFIC AIMS: The aim of this study is to determine whether quantitative measures of knee structures including effusion, bone marrow lesions, cartilage, and meniscal damage can improve upon an existing model of demographic and clinical characteristics to classify accelerated knee osteoarthritis (AKOA). METHODS/STUDY POPULATION: We conducted a case-control study using data from baseline and four annual follow-up visits from the osteoarthritis initiative. Participants had no radiographic knee osteoarthritis (KOA) at baseline. AKOA is defined as progressing from no KOA to advance-stage KOA in at least 1 knee within 48 months. AKOA knees were matched 1:1 based on sex to (1) participants who did not develop KOA within 48 months and (2) participants who developed KOA but not AKOA. Analyses were person based. Classification and regression tree analysis was used to determine the important variables and percent of variance explained. RESULTS/ANTICIPATED RESULTS: A previous classification and regression tree analysis found that age, BMI, serum glucose, and femorotibial angle explained 31% of the variability between those who did and did not develop AKOA. Including structural measurements as candidate variables yielded a model that included effusion, BMI, serum glucose, cruciate ligament degeneration and coronal slope and explained 39% of the variability. DISCUSSION/SIGNIFICANCE OF IMPACT: Knee structural measurements improve classification of participants who developed AKOA Versus those who did not. Further research is needed to better classify patients at risk for AKOA.
Because Plato's Philosophers: The Coherence of the Dialogues is such a monumental book, understanding its own coherence is a daunting task. The dialogue Theaetetus has as its theme the problem of knowledge, and so the part of Plato's Philosophers that deals with the Theaetetus seems a promising place to begin to think through what Zuckert's book means to be as a whole. In the Theaetetus we learn how knowledge, as a story that must begin and unfold for us in time, while necessarily partial, provides indirect, if imperfect, access to the whole and leads to a kind of self- knowledge. Plato makes this self-knowledge, the true goal of philosophy, most fully manifest in the drama of the life of his philosopher, Socrates, to which Plato's Philosophers, in meticulously tracing the dramatic order of the dialogues, means to provide access.
OBJECTIVES/SPECIFIC AIMS: To diversify the workforce by providing leadership and career coaching training to mentors so that they can be better leaders with their trainees and incorporate career coaching skills into their mentoring style. METHODS/STUDY POPULATION: PROMISED Program helps current and future members of the National Research Mentoring Network (NRMN) develop management, leadership, and career coaching skills so that they may be more effective in guiding their mentees. Studies show that mentees remain engaged in research when they drive their own careers, but mentors rarely help them recognize ways to do this. PROMISED aims to address by providing online leadership training and career coaching training. We developed innovative online leadership training for mentors committed to mentoring people from diverse backgrounds that are focused on management and leadership skills. These modules contain exercises, self-assessments, and discussion boards. We also have reading materials and other supplemental work such as videos to augment the modules. We also created 2-day training on career coaching skills for mentors. Certified career coaches trained participants in career coaching tools so that they could incorporate these skills into their mentoring style. Mentors tend to view themselves as content advisors, and they focus on the next step in the research project rather than the research career. We trained mentors to provide career coaching to their mentees, which will help the mentee establish a successful biomedical research career trajectory. RESULTS/ANTICIPATED RESULTS: In total, 45 mentors attended the Career Coaching Workshop. We assessed 26 mentoring/career coaching traits. Every trait improved on post survey (Likert scale 1–7), for example, “Taking into account the biases and prejudices you bring to the mentor/mentee relationship” (Pre: 4.16, Post: 5.38) and Working with mentees to set clear expectations of the mentoring relationship (Pre: 4.27, Post: 5.32). Some comments from attendees included: “amazing,” “powerful,” “excellent program,” “learned so much.” For the online module, we have a maximum of 20 fellows enrolled in each module. Results show that the fellows rate the module extremely useful. A comment from 1 fellow confirms this: “This session has changed my life and I know that the PROMISED program will transform my abilities as a mentor and as a person.” DISCUSSION/SIGNIFICANCE OF IMPACT: Providing Career Coaching Training and Online leadership skills can significantly improve mentors ability to mentor people, particularly those from diverse backgrounds. In addition, this training can help mentors who are committed to mentoring people from diverse backgrounds promote their own careers as well as their mentees.
Holocene tephrostratigraphy in Alaska provides independent chronology and stratigraphic correlation in a region where reworked old (Holocene) organic carbon can significantly distort radiocarbon chronologies. Here, we present new glass chemistry and chronology for Holocene tephras preserved in three Alaskan lakes: one in the eastern interior and two in the southern Brooks Range. Tephra beds in the eastern interior lake-sediment core are correlated with the White River Ash and the Hayes tephra set H (~4200–3700 cal yr BP), and an additional discrete tephra bed is likely from the Aleutian arc/Alaska Peninsula. Cryptotephras (nonvisible tephras) found in the Brooks Range include the informally named “Ruppert tephra” (~2700–2300 cal yr BP) and the Aniakchak caldera-forming event II (CFE II) tephra (~3600 cal yr BP). A third underlying Brooks Range cryptotephra is chemically indistinguishable from the Aniakchak CFE II tephra (4070–3760 cal yr BP) and is likely to be from an earlier eruption of the Aniakchak volcano.
A previously unresearched Early Bronze Age dagger-grave found in 1989 at Racton, West Sussex, is profiled here through a range of studies. The dagger, the only grave accompaniment, is of the ‘transitional’ Ferry Fryston type, this example being of bronze rather than copper. Bayesian analysis of relevant radiocarbon dates is used to refine the chronology of the earliest bronze in Britain. While the Ferry Fryston type was current in the earlier half of the twenty-second century bc, the first butt-riveted bronze daggers did not emerge until the second half. The Racton dagger is also distinguished by its elaborate rivet-studded hilt, an insular innovation with few parallels.
The excavated skeleton was that of a senior male, buried according to the appropriate rites of the time. Isotopic profiling shows an animal-protein rich diet that is typical for the period, but also the likelihood that he was brought up in a region of older silicate sedimentary rocks well to the west or north west of Racton. He had suffered injury at or close to the time of death; a slice through the distal end of his left humerus would have been caused by a fine-edged blade, probably a dagger. Death as a result of combat-contested leadership is explored in the light of other injuries documented among Early Bronze Age burials. Codified elite-level combat could help to explain the apparent incongruity between the limited efficacy of early dagger forms and their evident weapon-status.
In evaluating the insurance hypothesis as an explanation for obesity, we propose one missing piece of the puzzle. Our suggested explanation for why individuals report food insecurity is that an individual may have an impaired episodic ability to plan for the future.
Hip and knee arthroplasty infections are associated with considerable healthcare costs. The merits of reducing the postoperative surveillance period from 1 year to 90 days have been debated.
To report the first pan-Canadian hip and knee periprosthetic joint infection (PJI) rates and to describe the implications of a shorter (90-day) postoperative surveillance period.
Prospective surveillance for infection following hip and knee arthroplasty was conducted by hospitals participating in the Canadian Nosocomial Infection Surveillance Program (CNISP) using standard surveillance definitions.
Overall hip and knee PJI rates were 1.64 and 1.52 per 100 procedures, respectively. Deep incisional and organ-space hip and knee PJI rates were 0.96 and 0.71, respectively. In total, 93% of hip PJIs and 92% of knee PJIs were identified within 90 days, with a median time to detection of 21 days. However, 11%–16% of deep incisional and organ-space infections were not detected within 90 days. This rate was reduced to 3%–4% at 180 days post procedure. Anaerobic and polymicrobial infections had the shortest median time from procedure to detection (17 and 18 days, respectively) compared with infections due to other microorganisms, including Staphylococcus aureus.
PJI rates were similar to those reported elsewhere, although differences in national surveillance systems limit direct comparisons. Our results suggest that a postoperative surveillance period of 90 days will detect the majority of PJIs; however, up to 16% of deep incisional and organ-space infections may be missed. Extending the surveillance period to 180 days could allow for a better estimate of disease burden.
To determine the impact of total household decolonization with intranasal mupirocin and chlorhexidine gluconate body wash on recurrent methicillin-resistant Staphylococcus aureus (MRSA) infection among subjects with MRSA skin and soft-tissue infection.
Three-arm nonmasked randomized controlled trial.
Five academic medical centers in Southeastern Pennsylvania.
Adults and children presenting to ambulatory care settings with community-onset MRSA skin and soft-tissue infection (ie, index cases) and their household members.
Enrolled households were randomized to 1 of 3 intervention groups: (1) education on routine hygiene measures, (2) education plus decolonization without reminders (intranasal mupirocin ointment twice daily for 7 days and chlorhexidine gluconate on the first and last day), or (3) education plus decolonization with reminders, where subjects received daily telephone call or text message reminders.
MAIN OUTCOME MEASURES
Owing to small numbers of recurrent infections, this analysis focused on time to clearance of colonization in the index case.
Of 223 households, 73 were randomized to education-only, 76 to decolonization without reminders, 74 to decolonization with reminders. There was no significant difference in time to clearance of colonization between the education-only and decolonization groups (log-rank P=.768). In secondary analyses, compliance with decolonization was associated with decreased time to clearance (P=.018).
Total household decolonization did not result in decreased time to clearance of MRSA colonization among adults and children with MRSA skin and soft-tissue infection. However, subjects who were compliant with the protocol had more rapid clearance
The concepts of nature, culture and heritage are deeply entwined; their threads run together in some of our finest museums, in accounts of exploration and discovery, in the work of artists, poets andwriters, and in areas that are cherished and protected because of their landscapes and wildlife. The conservation ethic - placing a value on the natural environment - lies at the heart of the notion of "natural heritage", but we need to question how those values originated, were consolidated and ultimately moulded and changed over time. In a contemporary context the connections between nature andculture have sometimes become lost, fragmented, dislocated or misunderstood; where did "natural heritage" begin and how do we engage with the idea of "nature" today? The essays collected here re-evaluate the role of culture in developing the concept of natural heritage, reflecting on the shifts in its interpretation over the last 300 years.
Contributors: Martin Holdgate, Marie Addyman,E. Charles Nelson, Darrell Smith, Andrew Ramsey, Viktor Kouloumpis, Richard Milner, Gina Douglas, Penny Bradshaw, Arthur MacGregor, Chiara Nepi, Hannah Paddon, Stephen Hewitt, Gordon McGregor Reid, Ghillean T Prance, Peter Davis, Christopher Donaldson, Lucy McRobert, Sophie Darlington, Keith Scholey, Paul A. Roncken, Angus Lunn, Juliet Clutton-Brock, Tim Sands, Robert A. Lambert, James Champion,Erwin van Maanen, Heather Prince, Chris Loynes, Julie Taylor, Sarah Elmeligi, Samantha Finn, Owen Nevin, Jared Bowers, Kate Hennessy, Natasha Lyons, Mike Jeffries.