•New automated methods permit characterization of the full repertoire of an animal's behavior.•Quantification of dynamic sensory stimuli in combination with behavioral analysis will facilitate ...identification of the computations the nervous system performs to transform sensory responses into motor outputs.•Extensive genetic tools and a simple nervous system make worms and flies attractive model systems for harnessing the full power of these new computational methods to solve the mechanisms underlying sensorimotor transformations.
The development of new computational tools has recently opened up the study of natural behaviors at a precision that was previously unachievable. These tools permit a highly quantitative analysis of behavioral dynamics at timescales that are well matched to the timescales of neural activity. Here we examine how combining these methods with established techniques for estimating an animal's sensory experience presents exciting new opportunities for dissecting the sensorimotor transformations performed by the nervous system. We focus this review primarily on examples from Caenorhabditis elegans and Drosophila melanogaster—for these model systems, computational approaches to characterize behavior, in combination with unparalleled genetic tools for neural activation, silencing, and recording, have already proven instrumental for illuminating underlying neural mechanisms.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Social capital has been shown to positively influence a multitude of economic, political, and social outcomes. Yet the factors that affect long-run social capital formation remain poorly understood. ...Recent evidence suggests that early state formation, especially investments in state capacity, are positively associated with higher levels of contemporary social capital and other prosocial attitudes. The channels by which early state capacity leads to greater social capital over time are even less understood. We contribute to both questions using the spatial and temporal expansion of the US postal network during the 19th century. We first show that county-level variation in post office density is highly correlated with a bevy of historical and contemporary indicators of social capital (e.g., associational memberships, civic participation, health, and crime). This finding holds even when controlling for historical measures of development and contemporary measures of income, inequality, poverty, education, and race. Second, we provide evidence of an informational mechanism by which this early investment in infrastructural capacity affected long-run social capital formation. Namely, we demonstrate that the expansion of the postal network in the 19th century strongly predicts the historical and contemporary location of local newspapers, which were the primary mode of impersonal information transmission during this period. Our evidence sheds light on the role of the state in both the origins of social capital and the channels by which it persists. Our findings also suggest that the consequences of the ongoing decline in local newspapers will negatively affect social capital.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
"In this book Adam Banks uses the concept of the Digital Divide as a metonym for America's larger racial divide, in an attempt to figure out what meaningful access for African Americans to ...technologies and the larger American society can or should mean. He argues that African American rhetorical traditions - the traditions of struggle for justice and equitable participation in American society - exhibit complex and nuanced ways of understanding the difficulties inherent in the attempt to navigate through the seemingly impossible contradictions of gaining meaningful access to technological systems with the good they seem to make possible and at the same time resisting the exploitative impulses that such systems always seem to present."--BOOK JACKET.
Bundled Payments in Orthopaedics Rana, Adam J.; Bozic, Kevin J.
Clinical orthopaedics and related research,
02/2015, Volume:
473, Issue:
2
Journal Article
Peer reviewed
Open access
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UL, UM, UPUK, VKSCE, ZAGLJ
The choice between combined-modality therapy (CMT) and chemotherapy alone for early-stage Hodgkin lymphoma (HL) remains controversial. Our objective was to define factors affecting treatment ...selection and resulting survival outcomes in the United States.
We identified 20,600 patients treated with CMT or chemotherapy between 2003 and 2011 from the National Cancer Data Base. Factors affecting treatment selection were studied in a mixed-effects logistic model. Survival outcomes were compared using a propensity score analysis to account for indication bias.
Only 49.5% of patients received CMT, and this proportion steadily declined between 2003 (59.4%) and 2011 (45.2%), particularly in younger patients. Apart from classical prognostic factors (age, stage, tumor location, histology, comorbidities), treatment selection was significantly influenced by sex, black race, distance to facility, and type of insurance. Uninsured patients had the lowest odds of receiving CMT. A significant random effect related to facility-specific treatment preference was also evident. Estimated 5-year overall survival (OS) was 89.6%, and relative survival (RS) was 94.3%. After adjustment for guarantee-time and indication biases, CMT was associated with better OS (hazard ratio HR, 0.61; 95% CI, 0.53 to 0.70) and RS (excess HR, 0.42; 95% CI, 0.33 to 0.54) than chemotherapy alone. This effect was without significant heterogeneity in subset analysis and was not sensitive to unobserved confounding.
Socioeconomic factors affect selection of curative treatments in HL. Widespread abandonment of CMT beyond circumstances sanctioned by guidelines may affect survival. Further research should focus on developing strategies that minimize toxicity and access disparities without compromising survival.
Imaging Atherosclerosis Tarkin, Jason M; Dweck, Marc R; Evans, Nicholas R ...
Circulation research,
2016-February-19, 2016-Feb-19, 2016-02-19, 20160219, Volume:
118, Issue:
4
Journal Article
Peer reviewed
Open access
Advances in atherosclerosis imaging technology and research have provided a range of diagnostic tools to characterize high-risk plaque in vivo; however, these important vascular imaging methods ...additionally promise great scientific and translational applications beyond this quest. When combined with conventional anatomic- and hemodynamic-based assessments of disease severity, cross-sectional multimodal imaging incorporating molecular probes and other novel noninvasive techniques can add detailed interrogation of plaque composition, activity, and overall disease burden. In the catheterization laboratory, intravascular imaging provides unparalleled access to the world beneath the plaque surface, allowing tissue characterization and measurement of cap thickness with micrometer spatial resolution. Atherosclerosis imaging captures key data that reveal snapshots into underlying biology, which can test our understanding of fundamental research questions and shape our approach toward patient management. Imaging can also be used to quantify response to therapeutic interventions and ultimately help predict cardiovascular risk. Although there are undeniable barriers to clinical translation, many of these hold-ups might soon be surpassed by rapidly evolving innovations to improve image acquisition, coregistration, motion correction, and reduce radiation exposure. This article provides a comprehensive review of current and experimental atherosclerosis imaging methods and their uses in research and potential for translation to the clinic.
We present 5-year results from CheckMate 227 Part 1, in which nivolumab plus ipilimumab improved overall survival (OS) versus chemotherapy in patients with metastatic non-small-cell lung cancer, ...regardless of tumor programmed death ligand 1 (PD-L1) status.
Adults with stage IV/recurrent non-small-cell lung cancer without
mutations or
alterations and with tumor PD-L1 ≥ 1% or < 1% (n = 1739) were randomly assigned. Patients with tumor PD-L1 ≥ 1% were randomly assigned to first-line nivolumab plus ipilimumab, nivolumab alone, or chemotherapy. Patients with tumor PD-L1 < 1% were randomly assigned to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy. End points included exploratory 5-year results for efficacy, safety, and quality of life.
At a minimum follow-up of 61.3 months, 5-year OS rates were 24% versus 14% for nivolumab plus ipilimumab versus chemotherapy (PD-L1 ≥ 1%) and 19% versus 7% (PD-L1 < 1%). The median duration of response was 24.5 versus 6.7 months (PD-L1 ≥ 1%) and 19.4 versus 4.8 months (PD-L1 < 1%). Among patients surviving 5 years, 66% (PD-L1 ≥ 1%) and 64% (PD-L1 < 1%) were off nivolumab plus ipilimumab without initiating subsequent systemic anticancer treatment by the 5-year time point. Survival benefit continued after nivolumab plus ipilimumab discontinuation because of treatment-related adverse events, with a 5-year OS rate of 39% (combined PD-L1 ≥ 1% and < 1% populations). Quality of life in 5-year survivors treated with nivolumab plus ipilimumab was similar to that in the general US population through the 5-year follow-up. No new safety signals were observed.
With all patients off immunotherapy treatment for ≥ 3 years, nivolumab plus ipilimumab increased 5-year survivorship versus chemotherapy, including long-term, durable clinical benefit regardless of tumor PD-L1 expression. These data support nivolumab plus ipilimumab as an effective first-line treatment for patients with metastatic non-small-cell lung cancer.
Intolerance to oxygen is a key limitation in many reactions and particularly in controlled radical polymerizations. Here we introduce the use of enzymes such as glucose oxidase (GOx) to deoxygenate ...reversible addition–fragmentation chain transfer polymerizations (Enz-RAFT), facilitating the preparation of highly controlled polymers in vessels open to ambient oxygen. Because the removal of oxygen is so efficient, very low concentrations of GOx and initiator can be used, enabling excellent control which is demonstrated by pseudoliving polymerization kinetics and the preparation of multiblock copolymers with narrow molecular weight distributions (M w/M n < 1.15). GOx retains sufficient activity to facilitate polymerization not only in aqueous solutions but also in a range of water/organic solvent mixtures, and we demonstrate the use of this technique to perform open vessel Enz-RAFT polymerizations in various methanol and dioxane/water mixtures.
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IJS, KILJ, NUK, PNG, UL, UM
Women live on average longer than men but have greater levels of late-life morbidity. We have uncovered a substantial sex difference in the pathology of the aging gut in Drosophila. The intestinal ...epithelium of the aging female undergoes major deterioration, driven by intestinal stem cell (ISC) division, while lower ISC activity in males associates with delay or absence of pathology, and better barrier function, even at old ages. Males succumb to intestinal challenges to which females are resistant, associated with fewer proliferating ISCs, suggesting a trade-off between highly active repair mechanisms and late-life pathology in females. Dietary restriction reduces gut pathology in aging females, and extends female lifespan more than male. By genetic sex reversal of a specific gut region, we induced female-like aging pathologies in males, associated with decreased lifespan, but also with a greater increase in longevity in response to dietary restriction.
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