OBJECTIVES/SPECIFIC AIMS: Determine the effectiveness of a curriculum designed to teach doctoral students to use implementation science theories, models and frameworks in optimizing scientific, social, political, cultural and organizational impact METHODS/STUDY POPULATION: Analysis of Integrated Final Projects across three cohorts of doctoral students (N=30) to identify sub-disciplinary knowledge integration and application. RESULTS/ANTICIPATED RESULTS: Integrated Final Projects indicate that the integration of IS, Program Theory and Research design within semester two yields application of integrated, sub-disciplinary knowledge to research design, identification of mechanisms of action and the address of barriers and facilitators to implementation of findings. Future analysis will be conducted to determine the degree to which dissertations reflect a similar level of sub-disciplinary integration and focus on implementation within the appropriate service setting. DISCUSSION/SIGNIFICANCE OF IMPACT: Training future translational researchers to understand and use implementation science theories, models and frameworks can potentially result in narrowing the science-to-service gap.

A lack of motivation and anhedonia represent frequent and pervasive symptoms in depression, although with poor specificity. Historically described as a response bias, reward-related impairments in depression may account for the important aspects of the cognitive impairments associated with diagnosis of major depressive disorder. Reward processing is a broad psychological construct that can be parsed into 3 distinct components known as “reinforcement learning” (learning), “reward responsiveness” (liking), and “motivation to obtain a reward” (wanting). Depressed patients respond hyposensitively to reward and maladaptively to punishment: this pattern is related to a dysfunction in the frontostriatal systems modulated by the monoamine systems; seems to be observed in medicated and unmedicated patients with depression and in healthy individuals with high levels of anhedonia; and could be observed in patients with a history of depression, even when in full remission. Considered to be cognitive impairments, reward-related-impairments may also constitute part of an underlying neurobiological vulnerability to major depressive disorder (MDD). For example, the reward-related impairment is state dependent and, more or less, correlated with symptom severity in some studies but has also been proposed as being trait like, with endophenotype characteristics, possibly contributing to the persistence of the disease or treatment resistance. The 3 core aspects of reward processing have specific neurobiological correlates that involve the ventral and dorsal striatum, lateral habenula, ventral tegmental area, orbitofrontal cortex, anterior cingulate cortex, and ventromedial and dorsolateral prefrontal cortex. These structures underline the important role of the dopaminergic mesolimbic pathway, but glutamate and serotonin could also have an important role, at least in some aspects of reward-related impairments.

We examined guild structure and diversity in the mammalian biota of the Paleogene of Wyoming and Montana and the Neogene of Pakistan. Trophic structure was measured as frequency of generic diversity in each of the following trophic categories: insectivore, omnivore, frugivore, herbivore, and carnivore. Trophic categories were inferred from dental morphology.

Results are summarized below (see graphs). In Wyoming/Montana, the Paleocene is dominated by herbivores (from the orders Condylarthra, Multituberculata, and Pantodonta) and insectivores (“Proteutheria” and Proprimates). In the early Eocene, herbivores (Perissodactyla, Artiodactyla, and Rodentia), carnivores (Carnivora, Creodonta, and Mesonychia), and insectivores (“Proteutheria,” Proprimates, and Primates) dominate. At the beginning of the Eocene, carnivores and insectivores are more diverse than herbivores, but later, herbivores are more diverse. Adapid primates become an important frugivore element in the early Eocene. Herbivores are the most common group throughout the sequence, ranging from 30% to 75% of all specimens.

In the Siwaliks, herbivores (from Proboscidea, Rodentia, Perissodactyla, and Artiodactyla) dominate in generic diversity (70–80%), with artiodactyls consistently representing about 50% of herbivore genera. Circa 16 Ma, rodents appear and become an important herbivore group. At 14 Ma, bovid diversity increases dramatically. Specialized browsers (tragulids, giraffids) and grazers (suids) represent 25% to 35% of herbivore diversity throughout the sequence. Carnivores, represented by creodonts and true carnivores, range from 5% to 20% of generic diversity in the Siwaliks. At 11 Ma, carnivores increase in generic diversity with amphicyonid and hyaenid carnivores dominating the guild. Carnivores and insectivores are never as diverse in the Siwaliks as they are in the early Eocene of North America.

In mammalian assemblages, size distributions reflect conditions of vegetation and climate as well as biotic interactions among mammals. Paleogene (Wyoming/Montana) and Neogene (Siwalik) mammalian faunas depict strikingly different size distributions in the cenograms below (rank v. size of herbivorous and omnivorous species), because evolutionary increase to substantial size did not become widespread among lineages until the middle Eocene (after our record).

In the Paleocene to early Eocene, substantial faunal turnover with accompanying change in guild structure occurred with little change in size distributions. While maintaining relatively small sizes, lineages of modern mammalian orders replaced species from archaic groups. However, most mammalian lineages experienced size increase, especially through the Wasatchian (early Eocene).

From the middle to late Miocene, significant size increases occurred upsection within several families of Siwalik carnivores, artiodactyls, and rodents. Families of insectivores, primates, proboscideans, and perissodactyls exhibited little change in species sizes despite changes in species composition and number. The trend toward increasing size preceded the widespread development of C4 grasslands in the Siwaliks, suggesting that biotic rather than abiotic factors influenced the size increase.

Probiotic yogurt and milk supplemented with probiotics have been investigated for their role in ‘low-grade’ inflammation but evidence for their efficacy is inconclusive. This study explores the impact of probiotic yogurt on metabolic and inflammatory biomarkers, with a parallel study of gut microbiota dynamics. The randomised cross-over study was conducted in fourteen healthy, young men to test probiotic yogurt compared with milk acidified with 2 % d-(+)-glucono-δ-lactone during a 2-week intervention (400 g/d). Fasting assessments, a high-fat meal test (HFM) and microbiota analyses were used to assess the intervention effects. Baseline assessments for the HFM were carried out after a run-in during which normal milk was provided. No significant differences in the inflammatory response to the HFM were observed after probiotic yogurt compared with acidified milk intake; however, both products were associated with significant reductions in the inflammatory response to the HFM compared with the baseline tests (assessed by IL6, TNFα and chemokine ligand 5) (P<0·001). These observations were accompanied by significant changes in microbiota taxa, including decreased abundance of Bilophila wadsworthia after acidified milk (log 2-fold-change (FC)=–1·5, P adj=0·05) and probiotic yogurt intake (FC=–1·3, P adj=0·03), increased abundance of Bifidobacterium species after acidified milk intake (FC=1·4, P adj=0·04) and detection of Lactobacillus delbrueckii spp. bulgaricus (FC=7·0, P adj<0·01) and Streptococcus salivarius spp. thermophilus (FC=6·0, P adj<0·01) after probiotic yogurt intake. Probiotic yogurt and acidified milk similarly reduce postprandial inflammation that is associated with a HFM while inducing distinct changes in the gut microbiota of healthy men. These observations could be relevant for dietary treatments that target ‘low-grade’ inflammation.

Recent literature suggests that Ca supplements have adverse effects on cardiovascular health. The effects of a Ca-rich supplement administered alone or in combination with short-chain fructo-oligosaccharides (scFOS) on serum lipids in postmenopausal women were examined using secondary data from a 24-month double-blind randomised controlled study. A total of 300 postmenopausal women were randomly assigned to daily supplements of 800 mg of Ca (2·4 g Aquamin) (Ca), 800 mg of Ca with 3 g of scFOS (CaFOS) or control (maltodextrin) (MD). A full lipid profile, body composition, blood pressure and a range of cytokines were measured at baseline and after 24 months. Intention-to-treat ANCOVA assessed treatment effects between the groups. A significant time-by-treatment effect was observed for LDL and total cholesterol for the Ca and CaFOS groups, with both groups having lower LDL and total cholesterol concentrations compared with MD after 24 months. The control group had mean (5·2 mmol/l) total cholesterol concentrations above the normal range (≤5 mmol/l) at 24 months, whereas values remained within the normal range in the treatment groups. There was no significant treatment effect on HDL-cholesterol, TAG, body composition, blood pressure or cytokine concentrations at 24 months, with the exception of IL-4, where there was a significant increase in the CaFOS group compared with the placebo. This study demonstrates a lipid-lowering effect of both the Ca-rich supplement alone and the supplement with scFOS. At the 4-year follow-up, there was no significant difference between the groups for reported diagnosed cardiovascular conditions.

Shell artefacts in Island Southeast Asia have often been considered local variants of ground-stone implements, introduced in the Late Pleistocene from Mainland Southeast Asia. The discovery of a well-preserved Tridacna shell adze from Ilin Island in the Philippines, suggests, however, a different interpretation. Using radiocarbon dating, X-ray diffraction and stratigraphic and chronological placement within the archaeological record, the authors place the ‘old shell’ effect into context, and suggest that shell technology was in fact a local innovation that emerged in the early Middle Holocene. The chronology and distribution of these artefacts has significant implications for the antiquity of early human interaction between the Philippines and Melanesia. It may have occurred long before the migrations of Austronesian-speaking peoples and the emergence of the Lapita Cultural Complex that are traditionally thought to mark the first contact.

Studies have suggested that maternal PUFA status during pregnancy may influence early childhood allergic diseases, although findings are inconsistent. We examined the relationship between maternal PUFA status and risk of allergic diseases in early childhood in an Asian cohort. Maternal plasma samples from the Growing Up in Singapore Towards Healthy Outcomes mother–offspring cohort were assayed at 26–28 weeks of gestation for relative abundance of PUFA. Offspring (n 960) were followed up from 3 weeks to 18 months of age, and clinical outcomes of potential allergic diseases (rhinitis, eczema and wheezing) were assessed by repeated questionnaires. Skin prick testing (SPT) was also performed at the age of 18 months. Any allergic disease with positive SPT was defined as having any one of the clinical outcomes plus a positive SPT. The prevalence of a positive SPT, rhinitis, eczema, wheezing and any allergic disease with positive SPT was 14·1 % (103/728), 26·5 % (214/808), 17·6 % (147/833), 10·9 % (94/859) and 9·4 % (62/657), respectively. After adjustment for confounders, maternal total n-3, n-6 PUFA status and the n-6:n-3 PUFA ratio were not significantly associated with offspring rhinitis, eczema, wheezing, a positive SPT and having any allergic disease with positive SPT in the offspring (P>0·01 for all). A weak trend of higher maternal n-3 PUFA being associated with higher risk of allergic diseases with positive SPT in offspring was observed. These findings do not support the hypothesis that the risk of early childhood allergic diseases is modified by variation in maternal n-3 and n-6 PUFA status during pregnancy in an Asian population.