It has taken more than 40 years for the fields of immunology and neuroscience to capture the potential impact of the mechanistic understanding of how an active immune signalling brain might function. These developments have grown an appreciation for the immunocompetent cells of the central nervous system and their key role in the health and disease of the brain and spinal cord. Moreover, the understanding of the bidirectional communication between the brain and the peripheral immune system has evolved to capture an understanding of how mood can alter immune function and vice versa. These concepts are rapidly evolving the field of psychiatry and medicine as a whole. However, the advances in human medicine have not been capitalised upon yet in animal husbandry practice. Of specific attention are the implications that these biological systems have for creating and maintaining heightened pain states. This review will outline the key concepts of brain–immune communication and the immediate opportunities targeting this biology can have for husbandry practices, with a specific focus on pain.

OBJECTIVES/SPECIFIC AIMS: In an effort to elucidate the role of potentially cancer chemopreventive drugs, we leveraged the Mayo Clinic-Karolinska Institute collaboration to create a multidisciplinary team that included an epidemiologist, statisticians, and physicians. We performed a population-based cohort study to examine the association between low dose aspirin, non-aspirin NSAIDs, statins, metformin, other risk factors and the risk of biliary tract cancer (BTC), while assessing confounding by sex. METHODS/STUDY POPULATION: We conducted a nationwide Swedish population-based cohort study using the Swedish Prescribed Drug Registry, which virtually completely enumerates use of prescribed medications nationwide since 2005. BTC diagnosis (intrahepatic cholangiocarcinoma [iCCA], extrahepatic cholangiocarcinoma [eCCA] or gallbladder cancer [GBC]) was ascertained from the Swedish Cancer Registry. Age-scaled Cox models, with exposure as time-varying covariates, were used to calculate hazard ratios (HRs), separately for men and women. RESULTS/ANTICIPATED RESULTS: In the 5.7 million person cohort, the risk of iCCA was significantly lower in men using statins (HR 0.62,95%CI 0.39-1.00, p = 0.05), with a non-significant reduction in women. Statin use was associated with a significantly decreased risk of eCCA in both women (HR 0.60,0.38-0.94, p = 0.03) and men (HR 0.47,0.28-0.80, p = 0.01). Low dose aspirin (HR 0.76,0.60-0.97, p = 0.03) was associated with a lower risk of GBC only in women, while statins (HR 0.72,0.55-0.93, p = 0.01) showed a significantly decreased risk of GBC in women and a non-significant reduction in men. For all BTC subtypes, combined use of low dose aspirin and statins did not confer additional risk reductions beyond those achieved by statins alone. Male and female users of non-aspirin NSAIDs appeared to be at increased risk of BTC and its subtypes. Metformin did not significantly affect risk of BTC. DISCUSSION/SIGNIFICANCE OF IMPACT: Our collaborative efforts allowed us to develop the largest population-based cohort evaluating risk and protective factors for BTC. Our results provide strong evidence in favor of the chemopreventive roles of low dose aspirin and statins in a subtype- and sex-specific manner. Individual risk factors contribute to development of BTC subtypes in different magnitudes. The next steps to translate these findings into clinical practice require randomized clinical trials that validate our results and provide a more complete picture of the risk-benefit ratio.

While SrTiO3 exhibits promising electronic transport properties, its high thermal conductivity (κ) is detrimental for its use as a thermoelectric material. Here, we investigate the influence of oxygen non-stoichiometry on κ in bulk SrTiO3 ceramics. A significant reduction in κ was achieved in oxygen deficient SrTiO3−δ, owing to the presence of oxygen vacancies that act as phonon scattering centers. Upon oxidation of SrTiO3−δ, the κ of pristine SrTiO3 was recovered, suggesting that oxygen vacancies were indeed responsible for the reduction in κ. Raman spectroscopy was used as an independent tool to confirm the reduction of oxygen vacancies in SrTiO3−δ upon oxidation.

The illegal wildlife trade is driving declines in populations of a number of large, charismatic animal species but also many lesser known and restricted-range species, some of which are now facing extinction as a result. The ploughshare tortoise Astrochelys yniphora, endemic to the Baly Bay National Park of north-western Madagascar, is affected by poaching for the international illegal pet trade. To quantify this, we estimated population trends during 2006–2015, using distance sampling surveys along line transects, and recorded national and international confiscations of trafficked tortoises for 2002–2016. The results suggest the ploughshare tortoise population declined > 50% during this period, to c. 500 adults and subadults in 2014–2015. Prior to 2006 very few tortoises were seized either in Madagascar or internationally but confiscations increased sharply from 2010. Since 2015 poaching has intensified, with field reports suggesting that two of the four subpopulations are extinct, leaving an unknown but almost certainly perilously low number of adult tortoises in the wild. This study has produced the first reliable population estimate of the ploughshare tortoise and shows that the species has declined rapidly because of poaching for the international pet trade. There is an urgent need for increased action both in Madagascar and along international trade routes if the extinction of the ploughshare tortoise in the wild is to be prevented.

Moringa oleifera seeds are currently being used as a livestock feed across tropical regions of the world due to its availability and palatability. However, limited knowledge exists on the effects of the raw seeds on ruminant metabolism. As such, the rumen stimulation technique was used to evaluate the effects of substituting increasing concentrations of ground Moringa seeds (0, 100, 200 and 400 g/kg concentrate dry matter (DM)) in the diet on rumen fermentation and methane production. Two identical, Rusitec apparatuses, each with eight fermenters were used with the first 8 days used for adaptation and days 9 to 16 used for measurements. Fermenters were fed a total mixed ration with Urochloa brizantha as the forage. Disappearance of DM, CP, NDF and ADF linearly decreased (P<0.01) with increasing concentrations of Moringa seeds in the diet. Total volatile fatty acid production and the acetate to propionate ratio were also linearly decreased (P<0.01). However, only the 400 g/kg (concentrate DM basis) treatment differed (P<0.01) from the control. Methane production (%), total microbial incorporation of 15N and total production of microbial N linearly decreased (P<0.01) as the inclusion of Moringa seeds increased. Though the inclusion of Moringa seeds in the diet decreased CH4 production, this arose from an unfavourable decrease in diet digestibility and rumen fermentation parameters.

The Russian government is accused of hacking emails circulating among senior members of Hilary Clinton's campaign team to support President Trump's election in 2016. This was not the first time the United States was the target of massive cyber espionage: The Chinese government is believed to have gained sensitive information on 22.1 million US government employees through “cyber intrusions” in 2014. This Article will examine whether cyber espionage of this kind is unlawful under public international law and will conclude that it is. Specifically, such espionage can result in a violation of territorial sovereignty and will likely violate the principle of non-intervention in the internal affairs of other States. Yet, based on the controversial “clean-hands-doctrine,” past US actions in the realms of cyber espionage and intervention may well invalidate any claims it asserts against Russia or China.

Mothers who have experienced childhood maltreatment are more likely to have children also exposed to maltreatment, a phenomenon known as intergenerational transmission. Factors in the perinatal period may contribute uniquely to this transmission, but timing effects have not been ascertained. Using structural equation modeling with 1,016 mothers and their 2,032 children in the Environmental Risk Longitudinal Twin Study, we tested the mediating role of postpartum depression between maternal childhood maltreatment and a cascade of negative child outcomes, specifically child exposure to maltreatment, internalizing symptoms, and externalizing symptoms: (a) adjusting for later maternal depression, (b) comparing across sex differences, and (c) examining the relative role of maltreatment subtypes. Mothers who had been maltreated as children, especially those who had experienced emotional or sexual abuse, were at increased risk for postpartum depression. In turn, postpartum depression predicted children’s exposure to maltreatment, followed by emotional and behavioral problems. Indirect effects from maternal childhood maltreatment to child outcomes were robust across child sex and supported significant mediation through postpartum depression; however, this appeared to be carried by mothers’ depression beyond the postpartum period. Identifying and treating postpartum depression, and preventing its recurrence, may help interrupt the intergenerational transmission of maltreatment and its sequelae.

Adolescent psychotic experiences increase risk for schizophrenia and other severe psychopathology in adulthood. Converging evidence implicates urban and adverse neighborhood conditions in the etiology of adolescent psychotic experiences, but the role of young people's personal perceptions of disorder (i.e., physical and social signs of threat) in their neighborhood is unknown. This was examined using data from the Environmental Risk Longitudinal Twin Study, a nationally representative birth cohort of 2,232 British twins. Participants were interviewed at age 18 about psychotic phenomena and perceptions of disorder in the neighborhood. Multilevel, longitudinal, and genetically sensitive analyses investigated the association between perceptions of neighborhood disorder and adolescent psychotic experiences. Adolescents who perceived higher levels of neighborhood disorder were significantly more likely to have psychotic experiences, even after accounting for objectively/independently measured levels of crime and disorder, neighborhood- and family-level socioeconomic status, family psychiatric history, adolescent substance and mood problems, and childhood psychotic symptoms: odds ratio = 1.62, 95% confidence interval [1.27, 2.05], p < .001. The phenotypic overlap between adolescent psychotic experiences and perceptions of neighborhood disorder was explained by overlapping common environmental influences, rC = .88, 95% confidence interval [0.26, 1.00]. Findings suggest that early psychological interventions to prevent adolescent psychotic experiences should explore the role of young people's (potentially modifiable) perceptions of threatening neighborhood conditions.

Cognitive impairment has been identified as an important aspect of major depressive disorder (MDD). We tested two theories regarding the association between MDD and cognitive functioning using data from longitudinal cohort studies. One theory, the cognitive reserve hypothesis, suggests that higher cognitive ability in childhood decreases risk of later MDD. The second, the scarring hypothesis, instead suggests that MDD leads to persistent cognitive deficits following disorder onset. We tested both theories in the Dunedin Study, a population-representative cohort followed from birth to midlife and assessed repeatedly for both cognitive functioning and psychopathology. We also used data from the Environmental Risk Longitudinal Twin Study to test whether childhood cognitive functioning predicts future MDD risk independent of family-wide and genetic risk using a discordant twin design. Contrary to both hypotheses, we found that childhood cognitive functioning did not predict future risk of MDD, nor did study members with a past history of MDD show evidence of greater cognitive decline unless MDD was accompanied by other comorbid psychiatric conditions. Our results thus suggest that low cognitive functioning is related to comorbidity, but is neither an antecedent nor an enduring consequence of MDD. Future research may benefit from considering cognitive deficits that occur during depressive episodes from a transdiagnostic perspective.

Based on biophysical ice-core data collected in the landfast ice off Barrow, Alaska, USA, in 2002 and 2003, a one-dimensional ice–ocean ecosystem model was developed to determine the factors controlling the bottom-ice algal community. The data and model results revealed a three-stage ice-algal bloom: (1) onset and early slow growth stage before mid-March, when growth is limited by light; (2) fast growth stage with increased light and sufficient nutrients; and (3) decline stage after late May as ice algae are flushed out of the ice bottom. Stages 2 and 3 are either separated by a transition period as in 2002 or directly connected by ice melting as in 2003, when in situ light and nutrient enrichment experiments showed only light limitations. The modeled net primary production of ice algae (NPPAi) from March to June is 1.2 and 1.7 g Cm–2 for 2002 and 2003, respectively, within the range of previous observations. Model sensitivity studies found that overall NPPAi increased almost proportionally to the initial nutrient concentrations in the water column. A phytoplankton bloom (if it occurs as in 2002) would compete with ice algae for nutrients and lead to reduced NPPAi. About 45% of the NPPAi was exported to the shallow benthos.

Objectives: The present study constitutes the first randomized controlled trial to investigate the relation of lutein (L) and zeaxanthin (Z) to brain function using functional magnetic resonance imaging (fMRI). It was hypothesized that L and Z supplementation in older adults would enhance neural efficiency (i.e., reduce activation) and cognitive performance on a verbal learning task relative to placebo. Methods: A total of 44 community-dwelling older adults (mean age=72 years) were randomly assigned to receive either placebo or L+Z supplementation (12 mg/daily) for 1 year. Neurocognitive performance was assessed at baseline and post-intervention on an fMRI-adapted task involving learning and recalling word pairs. Imaging contrasts of blood-oxygen-level-dependent (BOLD) signal were created by subtracting active control trials from learning and recall trials. A flexible factorial model was employed to investigate the expected group (placebo vs. supplement) by time (baseline vs. post-intervention) interaction in pre-specified regions-of-interest. Results: L and Z appeared to buffer cognitive decline on the verbal learning task (Cohen’s d=.84). Significant interactions during learning were observed in left dorsolateral prefrontal cortex and anterior cingulate cortex (p < .05, family-wise-error corrected). However, these effects were in the direction of increased rather than decreased BOLD signal. Although the omnibus interaction was not significant during recall, within-group contrasts revealed significant increases in left prefrontal activation in the supplement group only. Conclusions: L and Z supplementation appears to benefit neurocognitive function by enhancing cerebral perfusion, even if consumed for a discrete period of time in late life. (JINS, 2018, 24, 77–90)

Here we report on the material chemistry following crystallization in the presence of water vapor of chlorinated formamidinium lead-triiodide (NH2CH = NH2PbI3−xClx) perovskite films. We found in-situ exposure to water vapor reduces, or possibly eliminates, the retention of chlorine (Cl) inside NH2CH = NH2PbI3−xClx crystals. There is a strong tendency toward Cl volatility, which indicates the sensitivity of these materials for their integration into solar cells. The requisite for additional efforts focused on the mitigation of water vapor is reported. Based on the in situ results, hot casting (<100 °C) in dry conditions demonstrates improved film coverage and Cl retention with efficiencies reaching 12.07%.

Objectives: The current study examines whether psychosocial outcomes following pediatric traumatic brain injury (TBI) vary as a function of children’s rejection sensitivity (RS), defined as their disposition to be hypersensitive to cues of rejection from peers. Methods: Children ages 8–13 with a history of severe TBI (STBI, n=16), complicated mild/moderate TBI (n=35), or orthopedic injury (OI, n=49) completed measures assessing self-esteem and RS on average 3.28 years post-injury (SD=1.33, range=1.25–6.34). Parents reported on their child’s emotional and behavioral functioning and social participation. Results: Regression analyses found moderation of group differences by RS for three outcomes: social participation, self-perceptions of social acceptance, and externalizing behavior problems. Conditional effects at varying levels of RS indicated that externalizing problems and social participation were significantly worse for children with STBI at high levels of RS, compared to children with OI. Social participation for the STBI group remained significantly lower than the OI group at mean levels of RS, but not at low levels of RS. At high levels of RS, self-perceptions of social acceptance were lower for children with moderate TBI compared to OI, but group differences were not significant at mean or low levels of RS. No evidence of moderation was found for global self-worth, self-perceptions of physical appearance or athletic ability, or internalizing problems. Conclusions: The findings highlight the salient nature of social outcomes in the context of varying levels of RS. These findings may have implications for the design of interventions to improve social outcomes following TBI. (JINS, 2017, 23, 451–459)

A robust collection of mammal, bird, fish, and shellfish remains from an 8,000-year residential sequence at Morro Bay, a small, isolated estuary on the central California coast, shows a strong focus on marine species during the Middle-Late Transition cultural phase (950–700 cal B.P.), which largely coincides with the Medieval Climatic Anomaly (MCA). Previous studies have provided modest evidence for increased fishing and rabbit hunting during the MCA in adjacent regions, but the Morro Bay findings suggest a distinctive marine-focused subsistence refugium during the period of drought. Specifically, the sequence shows striking all-time peaks in marine and estuarine birds, fish NISP/m3, and fish/deer + rabbits during the MCA. Heavy exploitation of fish, aquatic birds, rabbits, and shellfish suggests that the bow and arrow, which seems to have arrived in the area at this time, had little impact on local subsistence strategies.

Environmental exposures during pregnancy may increase breast cancer risk for mothers and female offspring. Tumor tissue assays may provide insight regarding the mechanisms. This study assessed the feasibility of obtaining tumor samples and pathology reports from mothers (F0) who were enrolled in the Child Health and Development Studies during pregnancy from 1959 to 1967 and their daughters (F1) who developed breast cancer over more than 50 years of follow-up. Breast cancer cases were identified through linkage to the California Cancer Registry and self-report. Written consent was obtained from 116 F0 and 95 F1 breast cancer survivors to access their pathology reports and tumor blocks. Of those contacted, 62% consented, 13% refused and 24% did not respond. We obtained tissue samples for 57% and pathology reports for 75%, and if diagnosis was made ⩽10 years we obtained tissue samples and pathology reports for 91% and 79%, respectively. Obtaining pathology reports and tumor tissues of two generations is feasible and will support investigation of the relationship between early-life exposures and molecular tumor markers. However, we found that more recent diagnosis increased the accessibility of tumor tissue. We recommend that cohorts request consent for obtaining future tumor tissues at study enrollment and implement real-time tissue collection to enhance success of collecting tumor samples and data.

We have observed the oxygen-rich SNR 1E 0102.2-7219 with the integral field spectrograph WiFeS at Siding Spring Observatory and discovered sulfur-rich ejecta for the first time. Follow-up deep DDT observations with MUSE on the VLT (8100 s on source) reaching down to a noise level of ~5 × 10−20ergs−1cm−2Å−1spaxel−1 have led to the additional discovery of fast-moving hydrogen as well as argon-rich and chlorine-rich material. The detection of fast-moving hydrogen knots challenges the interpretation that the progenitor of 1E 0102 was a compact core of a Wolf-Rayet star that had shed its entire envelope. In addition to the detection of hydrogen and the products of oxygen-burning, this unprecedented sharp (0.2″ spaxel size at ~0.7″ seeing) and deep MUSE view of an oxygen-rich SNR in the Magellanic Clouds reveals further exciting discoveries, including [Fe xiv]λ5303 and [Fe xi]λ7892 emission, which we associate with the forward shock. We present this exciting data set and discuss some of its implications for the explosion mechanism and nucleosynthesis of the associated supernova.