OBJECTIVES/GOALS: Osteoarthritis (OA) is a cartilage destroying disease. We are investigating abaloparatide (ABL) activation of parathyroid hormone receptor type 1 (PTH1R), which is expressed by articular chondrocytes in OA. We propose ABL treatment is chondroprotective in murine PTOA via stimulation of matrix production and inhibition of chondrocyte maturation. METHODS/STUDY POPULATION: 16-week-old C57BL/6 male mice received destabilization of the medial meniscus (DMM) surgery to induce knee PTOA. Beginning 2 weeks post-DMM, 40 μg/kg of ABL (or saline) was administered daily via subcutaneous injection and tissues were harvested after 6 weeks of daily injections and 8 weeks after DMM surgery. Harvested joint tissues were used for histological and molecular assessment of OA using three 5 μm thick sagittal sections from each joint, 50 μm apart, cut from the medial compartment of injured knees. Safranin O/Fast Green tissue staining and immunohistochemistry-based detection of type 10 collagen (Col10) and lubricin (Prg4) was performed using standard methods. Histomorphometric quantification of tibial cartilage area and larger hypertrophic-like cells was performed using the Osteomeasure system. RESULTS/ANTICIPATED RESULTS: Safranin O/Fast Green stained sections showed a decreased cartilage loss in DMM joints from ABL-treated versus saline-treated mice. Histomorphometric analysis of total tibial cartilage area revealed preservation of cartilage tissue on the tibial surface. Immunohistochemical analyses showed that upregulation of Col10 in DMM joints was mitigated in the cartilage of ABL-treated mice, and chondrocyte expression of Prg4 was increased in uncalcified cartilage areas in ABL-treated group. The Prg4 finding suggests a matrix anabolic effect that may counter OA cartilage loss. Quantification of chondrocytes in uncalcified and calcified tibial cartilage areas revealed a reduction in the number of larger hypertrophic-like cells in ABL treated mice, suggesting deceleration of hypertrophic differentiation. DISCUSSION/SIGNIFICANCE: Cartilage preservation/regeneration therapies would fill a critical unmet need. We demonstrate that an osteoporosis drug targeting PTH1R decelerates PTOA in mice. ABL treatment was associated with preservation of cartilage, decreased Col10, increased Prg4, and decreased number of large hypertrophic-like chondrocytes in the tibial cartilage.

This paper explores the interaction of informal constraints on human behaviour by examining the evolution of English football jerseys. The jersey provides an excellent setting to demonstrate how informal constraints emerge from formal rules and shape human behaviour. Customs, approved norms and habits are all observed in this setting. The commercialisation of football in recent decades has resulted in these informal constraints, in many cases dating back over a century, co-existing with branding, goodwill and identity effects. Combined, these motivate clubs to maintain the status quo. As a result, club colours have remained remarkably resilient within a frequently changing landscape.

The Late Triassic fauna of the Lossiemouth Sandstone Formation (LSF) from the Elgin area, Scotland, has been pivotal in expanding our understanding of Triassic terrestrial tetrapods. Frustratingly, due to their odd preservation, interpretations of the Elgin Triassic specimens have relied on destructive moulding techniques, which only provide incomplete, and potentially distorted, information. Here, we show that micro-computed tomography (μCT) could revitalise the study of this important assemblage. We describe a long-neglected specimen that was originally identified as a pseudosuchian archosaur, Ornithosuchus woodwardi. μCT scans revealed dozens of bones belonging to at least two taxa: a small-bodied pseudosuchian and a specimen of the procolophonid Leptopleuron lacertinum. The pseudosuchian skeleton possesses a combination of characters that are unique to the clade Erpetosuchidae. As a basis for investigating the phylogenetic relationships of this new specimen, we reviewed the anatomy, taxonomy and systematics of other erpetosuchid specimens from the LSF (all previously referred to Erpetosuchus). Unfortunately, due to the differing representation of the skeleton in the available Erpetosuchus specimens, we cannot determine whether the erpetosuchid specimen we describe here belongs to Erpetosuchus granti (to which we show it is closely related) or if it represents a distinct new taxon. Nevertheless, our results shed light on rarely preserved details of erpetosuchid anatomy. Finally, the unanticipated new information extracted from both previously studied and neglected specimens suggests that fossil remains may be much more widely distributed in the Elgin quarries than previously recognised, and that the richness of the LSF might have been underestimated.

The Interplay of Genes and Environment across Multiple Studies (IGEMS) is a consortium of 18 twin studies from 5 different countries (Sweden, Denmark, Finland, United States, and Australia) established to explore the nature of gene–environment (GE) interplay in functioning across the adult lifespan. Fifteen of the studies are longitudinal, with follow-up as long as 59 years after baseline. The combined data from over 76,000 participants aged 14–103 at intake (including over 10,000 monozygotic and over 17,000 dizygotic twin pairs) support two primary research emphases: (1) investigation of models of GE interplay of early life adversity, and social factors at micro and macro environmental levels and with diverse outcomes, including mortality, physical functioning and psychological functioning; and (2) improved understanding of risk and protective factors for dementia by incorporating unmeasured and measured genetic factors with a wide range of exposures measured in young adulthood, midlife and later life.

The National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry is one of the oldest, national population-based twin registries in the USA. It comprises 15,924 White male twin pairs born in the years 1917–1927 (N = 31.848), both of whom served in the armed forces, chiefly during World War II. This article updates activities in this registry since the most recent report in Twin Research and Human Genetics (Page, 2006). Records-based data include information from enlistment charts and Veterans Administration data linkages. There have been three major epidemiologic questionnaires and an education and earnings survey. Separate data collection efforts with the NAS-NRC registry include the National Heart, Lung, and Blood Institute (NHLBI) subsample, the Duke Twins Study of Memory in Aging and a clinically based study of Parkinson’s disease. Progress has been made on consolidating the various data holdings of the NAS-NRC Twin Registry. Data that had been available through the National Academy of Sciences are now freely available through National Archive of Computerized Data on Aging (NACDA).

The voting paradox occurs when a democratic society seeking to aggregate individual preferences into a social preference reaches an intransitive ordering. However it is not widely known that the paradox may also manifest for an individual aggregating over attributes of risky objects to form a preference over those objects. When this occurs, the relation ‘stochastically greater than’ is not always transitive and so transitivity need not hold between those objects. We discuss the impact of other decision paradoxes to address a series of philosophical and economic arguments against intransitive (cyclical) choice, before concluding that intransitive choices can be justified.

We retrospectively evaluated the effect of penicillin adverse drug reaction (ADR) labeling on surgical antibiotic prophylaxis. Cefazolin was administered in 86% of penicillin ADR-negative (−) and 28% penicillin ADR-positive (+) cases. Broad-spectrum antibiotic use was more common in ADR(+) cases and was more commonly associated with perioperative adverse drug events.

Introduction: Situational awareness (SA) is essential for maintenance of scene safety and effective resource allocation in mass casualty incidents (MCI). Unmanned aerial vehicles (UAV) can potentially enhance SA with real-time visual feedback during chaotic and evolving or inaccessible events. The purpose of this study was to test the ability of paramedics to use UAV video from a simulated MCI to identify scene hazards, initiate patient triage, and designate key operational locations. Methods: A simulated MCI, including fifteen patients of varying acuity (blast type injuries), plus four hazards, was created on a college campus. The scene was surveyed by UAV capturing video of all patients, hazards, surrounding buildings and streets. Attendees of a provincial paramedic meeting were invited to participate. Participants received a lecture on SALT Triage and the principles of MCI scene management. Next, they watched the UAV video footage. Participants were directed to sort patients according to SALT Triage step one, identify injuries, and localize the patients within the campus. Additionally, they were asked to select a start point for SALT Triage step two, identify and locate hazards, and designate locations for an Incident Command Post, Treatment Area, Transport Area and Access/Egress routes. Summary statistics were performed and a linear regression model was used to assess relationships between demographic variables and both patient triage and localization. Results: Ninety-six individuals participated. Mean age was 35 years (SD 11), 46% (44) were female, and 49% (47) were Primary Care Paramedics. Most participants (80 (84%)) correctly sorted at least 12 of 15 patients. Increased age was associated with decreased triage accuracy [-0.04(-0.07,-0.01);p=0.031]. Fifty-two (54%) were able to localize 12 or more of the 15 patients to a 27x 20m grid area. Advanced paramedic certification, and local residency were associated with improved patient localization [2.47(0.23,4.72);p=0.031], [-3.36(-5.61,-1.1);p=0.004]. The majority of participants (78 (81%)) chose an acceptable location to start SALT triage step two and 84% (80) identified at least three of four hazards. Approximately half (53 (55%)) of participants designated four or more of five key operational areas in appropriate locations. Conclusion: This study demonstrates the potential of UAV technology to remotely provide emergency responders with SA in a MCI. Additional research is required to further investigate optimal strategies to deploy UAVs in this context.

Campylobacteriosis, the most frequent bacterial enteric disease, shows a clear yet unexplained seasonality. The study purpose was to explore the influence of seasonal fluctuation in the contamination of and in the behaviour exposures to two important sources of Campylobacter on the seasonality of campylobacteriosis. Time series analyses were applied to data collected through an integrated surveillance system in Canada in 2005–2010. Data included sporadic, domestically-acquired cases of Campylobacter jejuni infection, contamination of retail chicken meat and of surface water by C. jejuni, and exposure to each source through barbequing and swimming in natural waters. Seasonal patterns were evident for all variables with a peak in summer for human cases and for both exposures, in fall for chicken meat contamination, and in late fall for water contamination. Time series analyses showed that the observed campylobacteriosis summer peak could only be significantly linked to behaviour exposures rather than sources contamination (swimming rather than water contamination and barbequing rather than chicken meat contamination). The results indicate that the observed summer increase in human cases may be more the result of amplification through more frequent risky exposures rather than the result of an increase of the Campylobacter source contamination.

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.

Nominative determinism occurs when a person's name reflects what that person does or is, for instance Mr Baker making bread or Ms Taylor making dresses. In the Potter saga J. K. Rowling seems to have a particular fondness for nominative determinism. In her case the names often derive from Latin and Greek language and tradition.