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Since the nineteenth century, studies of the human fossil record and human skeletal variation have made scientific rigor a valued goal. In the nineteenth and early twentieth centuries, this manifested itself in the creation of objective standards of measurement and observation (Boas 1899; Hrdlička 1919). More recent attempts have been made to further address the challenges of gathering standardized data from skeletal or fossil samples deriving from different populations, contexts, or taphonomic conditions (Buikstra and Ubelaker 1994). By the early twentieth century, the growth of available metric data required greater attention to the use of quantitative data in formal statistical analyses, often with the aim of explicit hypothesis testing (Morant 1939). Since the 1960s, multivariate statistical approaches have increasingly dominated the quantitative literature in evolutionary studies, accommodating ever-increasing data availability and increased computer processing capabilities (Howells 1969; Sokal and Rohlf 1981).
That almost half the Northern electorate continued to vote for Democrats is one of the worst understood aspects of the Civil War experience. In too many accounts of the war, Northern Democrats either do not figure at all, or do so only as morally blind obstructionists on the wrong side of history. Yet there is a case for saying that rather than being peripheral to the narrative of the war, Northern Democrats should be center stage. Because the route to Confederate victory lay in convincing the North that the cost of coercion was too high to be worth paying, the views and actions of that large and fluctuating group of white Northerners who had never joined the Republican bandwagon was crucial.
As new cannabis products and administration methods proliferate, patterns of use are becoming increasingly heterogeneous. However, few studies have explored different profiles of cannabis use and their association with problematic use.
Latent class analysis (LCA) was used to identify subgroups of past-year cannabis users endorsing distinct patterns of use from a large international sample (n = 55 240). Past-12-months use of six different cannabis types (sinsemilla, herbal, hashish, concentrates, kief, edibles) were used as latent class indicators. Participants also reported the frequency and amount of cannabis used, whether they had ever received a mental health disorder diagnosis and their cannabis dependence severity via the Severity of Dependence Scale (SDS).
LCA identified seven distinct classes of cannabis use, characterised by high probabilities of using: sinsemilla & herbal (30.3% of the sample); sinsemilla, herbal & hashish (20.4%); herbal (18.4%); hashish & herbal (18.8%); all types (5.7%); edibles & herbal (4.6%) and concentrates & sinsemilla (1.7%). Relative to the herbal class, classes characterised by sinsemilla and/or hashish use had increased dependence severity. By contrast, the classes characterised by concentrates use did not show strong associations with cannabis dependence but reported greater rates of ever receiving a mental health disorder diagnosis.
The identification of these distinct classes underscores heterogeneity among cannabis use behaviours and provides novel insight into their different associations with addiction and mental health.
To develop a physiological data-driven model for early identification of impending cardiac arrest in neonates and infants with cardiac disease hospitalised in the cardiovascular ICU.
We performed a single-institution retrospective cohort study (11 January 2013–16 September 2015) of patients ≤1 year old with cardiac disease who were hospitalised in the cardiovascular ICU at a tertiary care children’s hospital. Demographics and diagnostic codes of cardiac arrest were obtained via the electronic health record. Diagnosis of cardiac arrest was validated by expert clinician review. Minute-to-minute physiological monitoring data were recorded via bedside monitors. A generalized linear model was used to compute a minute by minute risk score. Training and test data sets both included data from patients who did and did not develop cardiac arrest. An optimal risk-score threshold was derived based on the model’s discriminatory capacity for impending arrest versus non-arrest. Model performance measures included sensitivity, specificity, accuracy, likelihood ratios, and post-test probability of arrest.
The final model consisting of multiple clinical parameters was able to identify impending cardiac arrest at least 2 hours prior to the event with an overall accuracy of 75% (sensitivity = 61%, specificity = 80%) and observed an increase in probability of detection of cardiac arrest from a pre-test probability of 9.6% to a post-test probability of 21.2%.
Our findings demonstrate that a predictive model using physiologic monitoring data in neonates and infants with cardiac disease hospitalised in the paediatric cardiovascular ICU can identify impending cardiac arrest on average 17 hours prior to arrest.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis a hereditary, multi-systemic and life-threatening disease resulting in neuropathy and cardiomyopathy. In the APOLLO study, patisiran, an investigational RNAi therapeutic targeting hepatic TTR production resulted in significant improvement in neuropathy and QoL compared to placebo and was generally well tolerated. Methods: APOLLO, a Phase 3 study of patisiran vs. placebo (NCT01960348) prespecified a cardiac subpopulation (n=126 of 225 total) that included patients with baseline left ventricular (LV) wall thickness ≥ 13mm and no medical history of aortic valve disease or hypertension. Cardiac measures included structure and function by electrocardiography, changes in NT-proBNP and 10-MWT gait speed. Results: At 18 months, patisiran treatment resulted in a mean reduction in LV wall thickness of 1 mm (p=0.017) compared to baseline, which was associated with significant improvements relative to placebo in LV end diastolic volume (+8.31 mL, p=0.036), global longitudinal strain (-1.37%, p=0.015) and NT-proBNP (55% reduction, p=7.7 x 10-8) (Figure 1). Gait speed was also improved relative to placebo (+0.35 m/sec, p=7.4 x 10-9). Rate of death or hospitalization was lower with patisiran. mNIS+7 results in the cardiac subpopulation will also be presented. Conclusions: These data suggest patisiran has the potential to halt or reverse cardiac manifestations of hATTR amyloidosis.
Childhood maltreatment is associated with increased risk for most forms of psychopathology. We examine emotion dysregulation as a transdiagnostic mechanism linking maltreatment with general psychopathology. A sample of 262 children and adolescents participated; 162 (61.8%) experienced abuse or exposure to domestic violence. We assessed four emotion regulation processes (cognitive reappraisal, attention bias to threat, expressive suppression, and rumination) and emotional reactivity. Psychopathology symptoms were assessed concurrently and at a 2-year longitudinal follow-up. A general psychopathology factor (p factor), representing co-occurrence of psychopathology symptoms across multiple internalizing and externalizing domains, was estimated using confirmatory factor analysis. Maltreatment was associated with heightened emotional reactivity and greater use of expressive suppression and rumination. The association of maltreatment with attention bias varied across development, with maltreated children exhibiting a bias toward threat and adolescents a bias away from threat. Greater emotional reactivity and engagement in rumination mediated the longitudinal association between maltreatment and increased general psychopathology over time. Emotion dysregulation following childhood maltreatment occurs at multiple stages of the emotion generation process, in some cases varies across development, and serves as a transdiagnostic mechanism linking child maltreatment with general psychopathology.
Ion-implantation has many applications in the fabrication and processing of microelectronic devices from semiconductors, but thermal treatments are required to remove defects produced by the implant and to electrically activate dopants. Recently, pulsed laser annealing has been used to activate surface layers of GaAs that have been heavily doped with 28Si+ by ion implantation, and carrier concentrations of > 1 x 1019 cm-3 have been achieved (Ref. 1). Double-crystal x-ray diffraction techniques are very sensitive to strains and defects in single crystals and provide a means for characterizing and quantifying the damage produced by ion-implantation and the subsequent relief of damage by pulsed laser annealing.
Many important scientific and technical problems are best addressed using multiple, microscopy-based analytical techniques that combine the strengths of complementary methods. Here, we provide two examples from biomedical challenges: unravelling the attachment zone between dental implants and bone, and uncovering the mechanism of Alzheimer's disease. They combine synchrotron-based scanning transmission X-ray microscopy (STXM) with transmission electron microscopy ((S)TEM), electron tomography (ET), EELS tomography, and/or atom probe tomography (APT). STXM provides X-ray absorption based chemical sensitivity at mesoscale resolution (10–30 nm), which complements higher spatial resolution electron microscopy and APT.
OBJECTIVES/SPECIFIC AIMS: Alzheimer’s disease (AD) is the leading cause of dementia, and a rapidly growing public health crisis as life expectancy increases. Two hallmark symptoms of the disease are memory impairment and the pathological accumulation of amyloid beta protein. The hippocampus is a brain region critical for the consolidation of new memories, and one of the first regions in which amyloid accumulation is observed. Our lab and others have observed a disruption to hippocampal network activity that is critical for memory consolidation in amyloid-accumulating mice. However, the mechanisms and neuronal micro-circuitry underlying this disruption are under-explored, a critical gap that warrants exploration if we are to understand memory disruption in the disease. In this study we have investigated the hypothesis that a preferential disruption to inhibitory PV neurons and the extracellular matrix that surrounds this cell type underlies downstream network alterations. METHODS/STUDY POPULATION: We have employed the 5xFAD mouse model of familial Alzheimer’s disease crossed with transgenic lines that selectively fluoresce in different neuronal sub-types. In a multi-modal approach, we have investigated behavioral, electrophysiological, and biochemical alterations between 3-month-old amyloid-accumulating 5xFAD mice and littermate controls. RESULTS/ANTICIPATED RESULTS: We observe a 35% increase in the incidence of synchronous hippocampal oscillations known as sharp wave ripples (SWRs) in amyloid-accumulating mice versus littermate controls (n = 28, p = 0.01), as well as a 95% increase in the power of slow gamma oscillations (p = 0.002). This hyperexcitability of the hippocampal network is correlated with an impairment in hippocampal-dependent memory, assayed with the Barnes Maze, a behavioral test of spatial memory (172% increase in latency to find escape hole, n = 8, p = 0.01). To elucidate the micro-circuitry that underlies this network disruption, we have investigated the integrity of peri-neuronal nets (PNNs), part of the extracellular matrix of proteins that preferentially ensheathe inhibitory PV neurons and support their function. We observe a 60% decrease in intensity of PNNs (n = 5, p = 0.005), suggesting PNN integrity is impaired in amyloid-accumulating mice. Ongoing experiments into the activity and synaptic input to both inhibitory PV and excitatory pyramidal neurons seek to determine the effects of this PNN disruption on downstream micro-circuitry. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that a preferential impairment to PNNs and inhibitory PV cells underlie hippocampal hyperexcitability in a mouse model of AD. As hippocampal network activity is critical for memory consolidation, these effects contribute to our understanding of memory disruption during early disease progression, which has been poorly understood to date. These findings provide a foundation for future in vivo studies employing optogenetic stimulation to this neuronal sub-type, to determine if restoring physiological network balance can ameliorate memory decline.
An innovative and valuable resource for understanding women's roles in changing societies, this book brings together the history of Africa, the Atlantic and gender before the 20th century. It explores trade, slavery and migration in the context of the Euro-African encounter.