Brandeis University
  • Waltham, United States
Recent publications
Previous research suggests creative ability peaks at ages between the mid 30s and early 40s, but has not focused on the role of age-related changes in cognitive abilities in this pattern. Cognitive processes show aging-related increases in experience-based knowledge (pragmatics or crystallized abilities) and decreases in the ability to process novel information quickly and efficiently (mechanics or fluid abilities). We explore the role of these age-related changes in the invention process, using a new database created by combining the publicly available patent data with information on inventor ages scraped from directory websites for approximately 1.2 million U.S.-resident inventors patenting between 1976 and 2017. We have made these data publicly available on the Harvard Dataverse and full documentation can be found in Kaltenberg et al. (2021) In the current paper, we present some descriptive statistics, and explore changing patterns of invention as inventor's age. For solo inventors, backward citations and originality increase with age, consistent with their being connected to crystallized intelligence. Forward citations, number of claims, and generality measures, as well as a citation-based measure of disruptiveness decline with inventor age, consistent with a connection to fluid intelligence. A similar pattern was found for performance in teams based on the average age of inventors in the team. Exploration of age diversity showed that teams with a wider age range had patents that are slightly more important (i.e., with more forward citations). Merging of these new data with other data that capture diverse aspects of inventors' environment and incentives offers rich potential for new research on invention.
The accurate simulation of additional interactions at the ATLAS experiment for the analysis of proton–proton collisions delivered by the Large Hadron Collider presents a significant challenge to the computing resources. During the LHC Run 2 (2015–2018), there were up to 70 inelastic interactions per bunch crossing, which need to be accounted for in Monte Carlo (MC) production. In this document, a new method to account for these additional interactions in the simulation chain is described. Instead of sampling the inelastic interactions and adding their energy deposits to a hard-scatter interaction one-by-one, the inelastic interactions are presampled, independent of the hard scatter, and stored as combined events. Consequently, for each hard-scatter interaction, only one such presampled event needs to be added as part of the simulation chain. For the Run 2 simulation chain, with an average of 35 interactions per bunch crossing, this new method provides a substantial reduction in MC production CPU needs of around 20%, while reproducing the properties of the reconstructed quantities relevant for physics analyses with good accuracy.
Access to the opioid antidote naloxone is a critical component of addressing the opioid crisis. Naloxone is a population-level prevention intervention associated with substantial reductions in overdose mortality and reduction of nonfatal overdose. Pharmacies' pivotal role in dispensing medications like buprenorphine for the treatment of opioid use disorder and selling nonprescription syringes places them at the crossroads of opioid access and risk mitigation methods like naloxone provision. Testing ways to optimize pharmacy-based naloxone provision will be key as the country expands the implementation of naloxone through the medical system. In the Respond to Prevent Study, we conducted a large, practical study of a pharmacy-focused intervention in a sample of Washington, Oregon, Massachusetts and New Hampshire community chain pharmacies to increase naloxone dispensing and improve opioid safety. The intervention integrated two evidence-based educational toolkits and streamlined materials to enhance the focus on naloxone policy, stigma reduction, and patient communications around naloxone, nonprescription syringes and buprenorphine access. The real-world study implemented a stepped wedge, clustered randomized trial design across 175 community chain pharmacies to evaluate the effectiveness of the Respond to Prevent intervention in increasing: (a) pharmacy based naloxone distribution rates, naloxone-related patient engagement, and pharmacist and technicians' attitudes, knowledge, perceived behavioral control and self-efficacy toward naloxone; and (b) pharmacy nonprescription syringe sales, and pharmacist and technicians' attitudes, knowledge, perceived behavioral control and self-efficacy toward dispensing buprenorphine for opioid use disorder (secondary outcomes). This commentary provides a brief narrative about the study and presents insights on the design and adaptations to our study protocol, including those adopted during the unprecedented COVID-19 pandemic further compounded by Western wildfires in 2020.
Background One fifth of the global burden of cardiovascular diseases (CVDs) in 2017 was attributable to excessive salt intake. As a member of the World Health Organization (WHO), Iran has committed itself to a 30% reduction in salt intake by 2025. Evidence on the amount and trend of salt intake among the Iranian population at national and sub-national levels is scarce. This study aimed to estimate the Iranian population’s salt intake during 2000–2016 at the national and sub-national levels, by sex and age groups. Methods Data on national and sub-national mean salt intake was obtained through systematically searching the literature and contacting the research studies’ principal investigators. Data collected through various methods were harmonized using the cross-walk method. Bayesian hierarchical and spatio-temporal-age regression models and simulation analysis were used to estimate the mean salt intake and its uncertainty interval across sex, age, year, and province. Results National age-sex standardized mean salt intake decreased from 10·53 g/day (95% uncertainty interval [UI]: 10·2 to 10·9) in 2000 to 9·41 (9·2 to 10·6) in 2016 (percent change: − 9·8% [− 21·1–3·1]). The age-standardized mean salt intake in women had decreased from 9·8 g/day (95% UI: 9·0–10·6) in 2000 to 9·1 g/day (8·6–9·7) in 2016 (percent change: − 6·6% [− 19·0–7·9]). The same measure in men was 11·1 g/day in 2000 (95% UI: 10·3–11·8) and 9·7 g/day (9·1–10·2) in 2016 (percent change: − 12·7% [− 23·0 – -0·9]). Age-sex standardized mean salt intake at the sub-national level in 2016 varied from 8·0 (95% UI: 7·0–9·0) to 10·5 (10·0–11·1). The difference between the provinces with the highest and the lowest levels of salt intake in 2016 was 31·3%. Conclusion Salt intake decreased in Iran from 2000 to 2016, while persistently exceeding the recommended values. This declining trend was more pronounced between 2010 and 2016, which might be attributed to Iran’s compliance to WHO’s Action Plan for reducing NCDs.
Small rhythmic circuits, such as those found in invertebrates, have provided fundamental insights into how circuit dynamics depend on individual neuronal and synaptic properties. Degenerate circuits are those with different network parameters and similar behavior. New work on degenerate circuits and their modulation illustrates some of the rules that help maintain stable and robust circuit function despite environmental perturbations. Advances in neuropeptide isolation and identification provide enhanced understanding of the neuromodulation of circuits for behavior. The advent of molecular studies of mRNA expression provides new insight into animal-to-animal variability and the homeostatic regulation of excitability in neurons and networks.
Purpose We described screening, brief intervention, and referral to treatment (SBIRT) results and assessed whether SBIRT is associated with positive changes in substance use, risky use, and educational/employment outcomes for youth in community-based settings that are not healthcare focused. Methods YouthBuild USA serves youth of ages 16–24 who are neither in school nor employed. In an SBIRT intervention, youth completed substance use surveys and Alcohol Use Disorders Identification Test and Drug Abuse Screening Test screenings at entry and program completion. Staff reported on services provided in response to screening scores. Regression models compared changes in youth screening results and substance use from intake to follow-up and, with aggregate program-level data, youth outcomes across programs with and without the SBIRT intervention. Results Youth significantly reduced Alcohol Use Disorders Identification Test (3.1 vs. 2.3, p < .001) and Drug Abuse Screening Test (1.9 vs. 1.4, p < .001) scores, positive screens (64% vs. 54%, p < .001), and need for referrals to treatment (48% vs. 37%, p < .001), indicating less risky substance use, although self-reports of substance use in the past 30 days did not decrease. Proportionately more youth in SBIRT programs attained a high school diploma or equivalent (49% vs. 42%, p = .01) and were still in educational/job placements 3 months after program completion (67% vs. 59%, p = .02), compared to youth in non-SBIRT programs. Discussion These findings suggest that community-based SBIRT is associated with positive outcomes–both reduced risky substance use and improved education and employment–that relate to longer-term positive development for youth. SBIRT appears to be an evidence-based approach to intervene and help youth.
What is the best way to ensure that scientific criticism is heard and understood?
Reliability refers to how measurements can produce consistent results and are crucial for any scientific research measurement. Intraclass Correlation Coefficient (ICC) is the most widely used method to determine the reproducibility of measurements of various statistical techniques. Calculated ICC and its confidence interval that reveal the underlying sampling distribution may help detect an experimental method's ability to identify systematic differences between research participants in a test. The purpose of this study was to introduce a new SAS macro, ICC6 for the calculation of different ICC forms and their confidence intervals. A SAS macro that employs the PROC GLM procedure in SAS was created to generate the estimates of two-way random effects (ANOVA). A simulated dataset was used as an input into the macro to calculate the point estimates for different types of ICCs. The upper and lower confidence interval limits for the ICC forms were calculated using the F statistics distribution. The SAS macro provided here produces a complete set of various forms of ICC along with their confidence intervals. A cross-validation using commercial software packages STATA and SPSS produced identical results. A development of SAS methodology using publicly available statistical approaches in estimating six distinct forms of ICC and their confidence intervals has been reported in this article. This work is an extension of available methodology supported by a few other statistical software packages to SAS.
Distinguished gerontologists, ‘guardians of later life’ who had long kept age and ageism at the heart of their work, were asked by the author why the turn to ageism had not been able to raise age consciousness more effectively in the media or the public. Their frank responses constitute a valuable archive of reflections about how intersectional concepts and activist passions develop in an emerging and contentious multi-disciplinary field. The essay further situates their learned critiques in the history of age studies over the last 30 years. Among the sorrowful and galvanizing revelations provoked by the Eldercide of the COVID-19 era is this: ‘ageism’ has become widely recognized as a keyword not only good to think with but necessary to act on.
Objective Previous research suggests a significant relationship between intimate partner violence (IPV) and HIV infection in women and that the risk of IPV is heightened in women with disabilities. Women with disabilities, particularly those residing in low-income and middle-income countries, may experience additional burdens that increase their vulnerability to IPV. We aimed to examine the association between having disability and HIV infection and the risk of IPV among women in South Africa. Design Using the 2016 South Africa Demographic and Health Survey, we calculated the prevalence of IPV and conducted modified Poisson regressions to estimate the unadjusted and adjusted risk ratios of experiencing IPV by disability and HIV status. Participants Our final analytical sample included 1269 ever-partnered women aged 18–49 years, who responded to the IPV module and received HIV testing. Results The prevalence of IPV was twice as high in women with disabilities with HIV infection compared with women without disabilities without HIV infection (21.2% vs 50.1%). Our unadjusted regression analysis showed that compared with women without disabilities without HIV infection, women with disabilities with HIV infection had almost four times higher odds (OR 3.72, 95% CI 1.27 to 10.9, p<0.05) of experiencing IPV. It appeared that women with disabilities with HIV infection experience compounded disparity. The association was compounded, with the OR for the combination of disability status and HIV status equal to or more than the sum of each of the individual ORs. Conclusions Women with disabilities and HIV infection are at exceptionally high risk of IPV in South Africa. Given that HIV infection and disability magnify each other’s risks for IPV, targeted interventions to prevent IPV and to address the complex and varied needs of doubly marginalised populations of women with disabilities with HIV infection are critical.
Here we show intranuclear nanoribbons formed upon dephosphorylation of leucine‐rich L‐ or D‐phosphopentapeptide catalyzed by alkaline phosphatase (ALP) to selectively kill osteosarcoma cells. Being dephosphorylated by ALP, the peptides firstly transformed into micelles and then convert into nanoribbons. The peptides/assemblies firstly aggregate on cell membrane, then enter cells via endocytosis, and finally accumulate in nuclei (mainly in nucleoli). Proteomics analysis suggests that the assemblies interact with histone proteins. The peptides kill osteosarcoma cells rapidly, and are nontoxic to normal cells. Moreover, the repeated stimulation of the osteosarcoma cells by the peptides sensitizes the cancer cells rather than inducing resistance. This work not only illustrates a novel mechanism for nucleus‐targeting, but also may lead a new way to selectively kill osteosarcoma cells and overcome drug resistance.
Memories are stored in the brain as cellular ensembles activated during learning and reactivated during retrieval. Using the Tet-tag system in mice, we label dorsal dentate gyrus neurons activated by positive, neutral or negative experiences with channelrhodopsin-2. Following fear-conditioning, these cells are artificially reactivated during fear memory recall. Optical stimulation of a competing positive memory is sufficient to update the memory during reconsolidation, thereby reducing conditioned fear acutely and enduringly. Moreover, mice demonstrate operant responding for reactivation of a positive memory, confirming its rewarding properties. These results show that interference from a rewarding experience can counteract negative affective states. While memory-updating, induced by memory reactivation, involves a relatively small set of neurons, we also find that activating a large population of randomly labeled dorsal dentate gyrus neurons is effective in promoting reconsolidation. Importantly, memory-updating is specific to the fear memory. These findings implicate the dorsal dentate gyrus as a potential therapeutic node for modulating memories to suppress fear.
Developmental experiences play critical roles in shaping adult physiology and behavior. We and others previously showed that adult C. elegans which transiently experienced dauer arrest during development (PD: post-dauer) exhibit distinct gene expression profiles as compared to control adults which bypassed the dauer stage. In particular, the expression patterns of subsets of chemoreceptor genes are markedly altered in PD adults. Whether altered chemoreceptor levels drive behavioral plasticity in PD adults is unknown. Here we show that PD adults exhibit enhanced attraction to a panel of food-related attractive volatile odorants including the bacterially-produced chemical diacetyl. Diacetyl-evoked responses in the AWA olfactory neuron pair are increased in both dauer larvae and PD adults, and we find that these increased responses are correlated with upregulation of the diacetyl receptor ODR-10 in AWA likely via both transcriptional and post-transcriptional mechanisms. We show that transcriptional upregulation of odr-10 expression in dauer larvae is in part mediated by the DAF-16 FOXO transcription factor. Via transcriptional profiling of sorted populations of AWA neurons from control and PD adults, we further show that the expression of a subset of additional chemoreceptor genes in AWA is regulated similarly to odr-10 in PD animals. Our results suggest that developmental experiences may be encoded at the level of olfactory receptor regulation, and provide a simple mechanism by which C. elegans is able to precisely modulate its behavioral preferences as a function of its current and past experiences.
Biodiversity conservation efforts have been criticized for generating inequitable socio‐economic outcomes. These equity challenges are largely analyzed as place‐based problems affecting local communities directly impacted by conservation programs. The conservation of migratory species extends this problem geographically since people in one place may benefit while those in another bear the costs of conservation. The spatial subsidies approach offers an effective tool for analyzing such relationships between places connected by migratory species. Designed to quantify ecosystem services provided and received in specific locations across a migratory species’ range—and the disparities between them—the spatial subsidies approach highlights three axes of inequity: between indigenous and settler colonial societies, between urban and rural populations, and between the Global North and Global South. Recognizing these relationships is critical to achieving two mutually reinforcing policy goals: avoiding inequitable conservation outcomes in efforts to conserve migratory species, and ensuring effective long‐term conservation of migratory species. In demonstrating how the spatial subsidies approach enables the identification and quantification of inequities involving three migratory species (northern pintail ducks, monarch butterflies, and Mexican free‐tailed bats), we argue that a spatial subsidies approach could apply to migratory species conservation efforts worldwide under the context of “payments for ecosystem services.”
Bit threads are curves in holographic spacetimes that manifest boundary entanglement, and are represented mathematically by continuum analogues of network flows or multiflows. Subject to a density bound, the maximum number of threads connecting a boundary region to its complement computes the Ryu–Takayanagi entropy. When considering several regions at the same time, for example in proving entropy inequalities, there are various inequivalent density bounds that can be imposed. We investigate for which choices of bound a given set of boundary regions can be “locked”, in other words can have their entropies computed by a single thread configuration. We show that under the most stringent bound, which requires the threads to be locally parallel, non-crossing regions can in general be locked, but crossing regions cannot, where two regions are said to cross if they partially overlap and do not cover the entire boundary. We also show that, under a certain less stringent density bound, a crossing pair can be locked, and conjecture that any set of regions not containing a pairwise crossing triple can be locked, analogously to the situation for networks.
Semiempirical quantum mechanical methods (SEQMs) are widely used in computational chemistry because of their low computational cost, but their accuracy depends on the quality of the parameters. The neglect of diatomic differential overlap method PM7 is among the few SEQMs that contain parameters for Ag, but the experimental reference data was insufficient to obtain reliable parameters in the original parametrization. In this work, we reparametrize the PM7 parameters for Ag to accurately reproduce the ground-state potential energy surfaces of Ag clusters. Since little experimental data is available, we use reference data obtained from the ab initio method CCSD(T). The resulting parameters significantly reduce the errors in binding energies, energies required to displace clusters along their normal modes, and relative energies of isomers compared to the default PM7 Ag parameters.
For the first time since 1860, our collective future as an ideologically coherent and nominally democratic nation is at risk. In the short, medium, and long term, our nation faces several systemic and intertwined threats. Because these cascading crises threaten our fundamental political ideals and our lives, we recommend here a rapid and careful reorientation of at least some part of American political development (APD) toward a scholarship of foresight—that is, one based on the premise that anticipating and shaping the future is now as important as or more important than understanding the past. The article first considers some of the ways in which APD is tethered to the past and then discusses how several of the subfield's analytical approaches are compatible with a scholarship of foresight. Prognosis, prediction, and projection, we argue, are analytical tools that can inform prescription. We conclude with five sets of recommendations that can help APD scholars consider turning their attention toward the future.
The econometrics literature has generally approached problems of causal inference from the perspective of obtaining an unbiased estimate of a parameter in a structural equation model. This requires strong assumptions about the functional form of the model and data distributions. As described in Chapter 3, there is a rapidly growing literature that has used machine learning to estimate causal effects. Machine learning models generally require far fewer assumptions. Traditionally, the identification of causal effects in econometric models rests on theoretically justified controls for observed and unobserved confounders. The high dimensionality of many datasets offers the potential for using machine learning to uncover potential instruments and expand the set of observable controls. Health care is an example of high dimensional data where there are many causal inference problems of interest. Epidemiologists have generally approached such problems using propensity score matching or inverse probability treatment weighting within a potential outcomes framework. This approach still focuses on the estimation of a parameter in a structural model. A more recent method, known as doubly robust estimation, uses mean differences in predictions versus their counterfactual that have been updated by exposure probabilities. Targeted maximum likelihood estimators (TMLE) optimize these methods. TMLE methods are not, inherently, machine learning methods. However, because the treatment effect estimator is based on mean differences in individual predictions of outcomes for those treated versus the counterfactual, super learning machine learning approaches have superior performance relative to traditional methods. In this chapter, we begin with the same assumption of selection of observable variables within a potential outcomes framework. We briefly review the estimation of treatment effects using inverse probability treatment weights and doubly robust estimators. These sections provide the building blocks for the discussion of TMLE methods and their estimation using super learner methods. Finally, we consider the extension of the TMLE estimator to include instrumental variables in order to control for bias from unobserved variables correlated with both treatment and outcomes.
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Raphael Schoenle
  • Department of Economics
James Hendrickson
  • Department of Chemistry
Yara Halasa
  • Schneider Institute for Health Policy
Arnold Kamis
  • International Business School
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