To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
ABSTRACT IMPACT: This study will provide the essential characterization of intrinsic neural activity in human brain organoids, both at the single cell and network levels, to harness for translational purposes. OBJECTIVES/GOALS: Brain organoids are 3D, stem cell-derived neural tissues that recapitulate neurodevelopment. However, to levy their full translational potential, a deeper understanding of their intrinsic neural activity is essential. Here, we present our preliminary analysis of maturing neural activity in human forebrain organoids. METHODS/STUDY POPULATION: Forebrain organoids were generated from human iPSC lines derived from healthy volunteers. Linear microelectrode probes were employed to record spontaneous electrical activity from day 77, 100, and 130 organoids. Single unit recordings were collected during hour-long recordings, involving baseline recordings followed by glutamatergic blockade. Subsequently, tetrodotoxin, was used to abolish action potential firing. Single units were identified via spike sorting, and the spatiotemporal evolution of baseline neural properties and network dynamics was characterized. RESULTS/ANTICIPATED RESULTS: Nine organoids were recorded successfully (n=3 per timepoint). A significant difference in number of units was seen across age groups (F (2,6) = 6.4178, p = 0.0323). Post hoc comparisons by the Tukey HSD test showed significantly more units in day 130 (51.67 ±14.15) than day 77 (16.33 ±14.98) organoids. Mean firing rates were significantly different in organoids based on age, with drug condition also trending toward significance (F (6,12) = 9.97; p = 0.0028 and p = 0.08 respectively). Post hoc comparisons showed a higher baseline firing rate in day 130 (0.99Hz ±0.30) organoids than their day 77 counterparts at baseline (0.31Hz ±0.066) and glutamate blockade (0.31Hz ±0.045). Preliminary network analysis showed no modularity or small-world features; however, these features are expected to emerge as organoids mature. DISCUSSION/SIGNIFICANCE OF FINDINGS: Initial analysis of brain organoid activity demonstrates changes in single unit properties as they mature. Additional work in this area, as well as further network analyses, will confer better sense of how to rationally utilize brain organoids for translational purposes.
Uninsured patients are more likely than the general population to use tobacco and less likely to quit.
To determine if the mode of delivering the PHS Guidelines influenced the effectiveness of smoking cessation among patients in a safety net setting.
Six free clinics were randomly assigned to a training program delivered by an academic physician or community partner plus video support. A repeated cross-sectional survey of patients was conducted at three waves to assess effectiveness to promote quitting.
Tobacco use was triple the rate of the US population: 57.7% (Wave 1), 44.7% (Wave 2), and 48.9% (Wave 3). Patients were more likely to report receipt of at least one evidence-based strategy to promote quitting at Wave 2 (AOR = 2.33, 95% CI (1.18–4.58)). Patients treated in clinics trained by the community partner were significantly more likely to report receiving cessation assistance at Wave 2 (AOR 2.54, 95%CI 1.29–5.00) and the trend was similar, but not significant at Wave 3. Patients in the community partner-led arm were significantly less likely to report tobacco use at Wave 3 (AOR 0.59, 95% CI 0.35–0.99).
Implementation of the PHS Guidelines in free clinics demonstrates preliminary efficacy, with delivery by community partners offering greater scalability.
We present a model of political networks that integrates both the choice of trade partners (the extensive margin) and trade volumes (the intensive margin). Our model predicts that regimes secure in their survival, including democracies as well as some consolidated authoritarian regimes, will trade more on the extensive margin than vulnerable autocracies, which will block trade in products that would expand interpersonal contact among their citizens. We apply a two-stage Bayesian LASSO estimator to detailed measures of institutional features and highly disaggregated product-level trade data encompassing 131 countries over a half century. Consistent with our model, we find that (a) political institutions matter for the extensive margin of trade but not for the intensive margin and (b) the effects of political institutions on the extensive margin of trade vary across products, falling most heavily on those goods that involve extensive interpersonal contact.
We introduce a model that extends the standard vote choice model to encompass text. In our model, votes and speech are generated from a common set of underlying preference parameters. We estimate the parameters with a sparse Gaussian copula factor model that estimates the number of latent dimensions, is robust to outliers, and accounts for zero inflation in the data. To illustrate its workings, we apply our estimator to roll call votes and floor speech from recent sessions of the US Senate. We uncover two stable dimensions: one ideological and the other reflecting to Senators’ leadership roles. We then show how the method can leverage common speech in order to impute missing data, recovering reliable preference estimates for rank-and-file Senators given only leadership votes.
Neuroticism, a ‘Big Five’ personality trait, has been associated with sub-clinical traits of both autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). The objective of the current study was to examine whether causal overlap between ASD and ADHD traits can be accounted for by genetic and environmental risk factors that are shared with neuroticism. We performed twin-based structural equation modeling using self-report data from 12 items of the Neo Five-Factor Inventory Neuroticism domain, 11 Social Responsiveness Scale items, and 12 Adult ADHD Self-Report Scale items obtained from 3,170 young adult Australian individual twins (1,081 complete pairs). Univariate analysis for neuroticism, ASD, and ADHD traits suggested that the most parsimonious models were those with additive genetic and unique environmental components, without sex limitation effects. Heritability of neuroticism, ASD, and ADHD traits, as measured by these methods, was moderate (between 40% and 45% for each respective trait). In a trivariate model, we observed moderate phenotypic (between 0.45 and 0.62), genetic (between 0.56 and 0.71), and unique environmental correlations (between 0.37and 0.55) among neuroticism, ASD, and ADHD traits, with the highest value for the shared genetic influence between neuroticism and self-reported ASD traits (rg = 0.71). Together, our results suggest that in young adults, genetic, and unique environmental risk factors indexed by neuroticism overlap with those that are shared by ASD and ADHD.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
Background: Delirium is common in critically ill patients and its presence is associated with increased mortality and increased likelihood of poor cognitive function among survivors. However, the cause of delirium is unknown. The purpose of this study was to demonstrate the feasibility of using near-infrared spectroscopy (NIRS) to assess brain tissue oxygenation in patients with septic shock, who are at high risk of developing delirium. Methods: This prospective observational study was conducted in a 33-bed general medical surgical intensive care unit (ICU). Patients with severe sepsis or septic shock were eligible for recruitment. The FORESIGHT NIRS monitor was used to assess brain tissue oxygenation in the frontal lobes for the first 72 hours of ICU admission. Physiological data was also recorded. We used the Confusion Assessment Method-ICU to screen for delirium.Results: From March 1st 2014-September 30th 2014, 10 patients with septic shock were recruited. The NIRS monitor captured 81% of the available data. No adverse events were recorded. Brain tissue oxygenation demonstrated significant intra- and inter-individual variability in the way it correlated with physiological parameters, such as mean arterial pressure, heart rate, and peripheral oxygen saturation. Mean brain tissue oxygen levels were significantly lower in patients who were delirious for the majority of their ICU stay. Conclusion: It is feasible to record brain tissue oxygenation with NIRS in patients with septic shock. This study provides the infrastructure necessary for a larger prospective observational study to further examine the relationship between brain tissue oxygenation, physiological parameters, and acute neurological dysfunction.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
A high-resolution rock magnetic investigation was performed on the Chaona Quaternary loess/paleosol sequences in the Central Chinese Loess Plateau. Based on a newly developed independent unturned time scale and magnetic records, we reconstructed the history of the East Asia monsoons during the last 3 Ma and explored the middle Pleistocene climate transition (MPT). Rock magnetic results show that the loess layers are characterized by relatively high coercivity and remanent coercivity, lower magnetic susceptibility (MS), and that the paleosol layers are characterized by relatively high MS, saturation magnetization and remanent saturation magnetization. Spectrum analyses indicate that there are various periods in addition to orbital periodicities. According to the onset and stable appearance of 100 kyr period, we consider that the MPT recorded in this section began at ~ 1.26 Ma and was completed by ~ 0.53 Ma, which differs from previous investigations based on orbitally tuned time scales. The forcing mechanism for the MPT was more complicated than just the orbital forcing. We conclude that the rapid uplift of the Tibetan Plateau may have played an important role in the shift of periodicities during the middle Pleistocene.
To examine the effects of complex cognitive (mahjong) and physical (Tai Chi) activities on dementia severity in nursing home residents with dementia.
Cluster-randomized open-label controlled design. 110 residents were randomized by nursing home into three conditions: mahjong, Tai Chi, and simple handicrafts (control). Activities were conducted three times a week for 12 weeks. Clinical Dementia Rating (CDR) was taken at 0 (baseline), 3 (post-treatment), 6, and 9 months. The outcome measure was CDR sum-of-box, which is a composite measure of both cognitive and functional deterioration in dementia.
Intent-to-treat analyses were performed using multilevel regression models. Apolipoprotein E ε4 allele and education were included as covariates. Neither treatments had effects on the cognitive and functional components of the CDR, but mahjong had a significant interaction with time on the CDR sum-of-box total, suggesting a slower rate of global deterioration in the mahjong group as compared with the control group.
Mahjong led to a gradual improvement in global functioning and a slightly slower rate of dementia progression over time. The effect was generalized and was not specific to cognition or daily functioning.
What is the future of criminal justice in the United States? There is ample room for pessimism, especially with the constitutional aspects of criminal law. No one doubts that the Warren Court era of the early 1950s through the 1960s was a high point for the constitutional rights of criminal defendants. Nor is there serious dispute that, on balance, the Supreme Court since then has adopted a more restrained attitude toward the constitutional rights of criminal defendants.
Changes in constitutional criminal law reflect more than judicial appointments and judicial attitudes, however. They also derive from political decisions and popular attitudes. Since the mid-1960s, national and local politicians have tended to support the idea of a “war on crime” that puts a premium on toughness toward lawbreaking and offenders (or suspected offenders) at the expense of individual rights. By and large, the voting public has supported these efforts.
The political decisions associated with the war on crime have had several
concrete and negative results. More and more conduct has been criminalized,
often through multiple statutes that define overlapping crimes (sometimes
overlapping state and federal crimes) for the same basic conduct.
Incarceration rates have expanded, especially among young black men; maximum
and supermax security prisons have proliferated; mandatory minimums
ensure lengthy prison sentences for nearly all felonies in many jurisdictions;
and the consequences of criminal convictions are dire. Police and prosecutors
continue to enjoy wide discretion to control the outcomes of criminal
cases, and the development of new surveillance technologies expands their
ability to gather evidence in ways that erode traditional notions of personal
privacy. Politicians and commentators urge people to live in fear of violent
crime and to be suspicious of people who act in unusual ways or who just
seem to be out of place. Undocumented immigrants automatically become criminals through the act of crossing a national border. These developments
are important in their own right; they are also causes and effects of judicial
decisions to rethink the scope of constitutional rights and other constitutional
and structural limitations on criminal law and punishment.