New Directions in Federal Land Use Legislation

The 1960\u27s, a decade that began with enthusiasm and ended in dashed hopes for many social planners, encompassed rising environmental expectations that did not fade with the decade, but grew stronger and contributed to several notable legislative breakthroughs. The new laws which the environmental awareness brought about were not only pollution control measures but extended to such issues as coastal zone protection, power plant siting, scenic area preservation and highway planning. The concern with protecting environmental values in land underlay the enactment of several state laws which have been referred to as a quiet revolution in land use control, a revolution that has returned land use regulatory power to the several states. Now this revolution has reached Washington where the Senate has passed legislation which would fundamentally alter governmental relationships regarding land use planning and regulation in the United States. Objectives which writers on urban and social problems have long advocated, but which the constituency for planning and housing has never been able to effectuate, stand a fair chance of achievement under the environmental aegis, as O\u27Harrow apparently anticipated

Distinct neuropeptide-receptor modules regulate a sex-specific behavioral response to a pheromone

Dioecious species are a hallmark of the animal kingdom, with opposing sexes responding differently to identical sensory cues. Here, we study the response of C. elegans to the small-molecule pheromone, ascr#8, which elicits opposing behavioral valences in each sex. We identify a novel neuropeptide-neuropeptide receptor (NP/NPR) module that is active in males, but not in hermaphrodites. Using a novel paradigm of neuropeptide rescue that we established, we leverage bacterial expression of individual peptides to rescue the sex-specific response to ascr#8. Concurrent biochemical studies confirmed individual FLP-3 peptides differentially activate two divergent receptors, NPR-10 and FRPR-16. Interestingly, the two of the peptides that rescued behavior in our feeding paradigm are related through a conserved threonine, suggesting that a specific NP/NPR combination sets a male state, driving the correct behavioral valence of the ascr#8 response. Receptor expression within pre-motor neurons reveals novel coordination of male-specific and core locomotory circuitries

Exploiting Large Neuroimaging Datasets to Create Connectome-Constrained Approaches for more Robust, Efficient, and Adaptable Artificial Intelligence

Despite the progress in deep learning networks, efficient learning at the edge (enabling adaptable, low-complexity machine learning solutions) remains a critical need for defense and commercial applications. We envision a pipeline to utilize large neuroimaging datasets, including maps of the brain which capture neuron and synapse connectivity, to improve machine learning approaches. We have pursued different approaches within this pipeline structure. First, as a demonstration of data-driven discovery, the team has developed a technique for discovery of repeated subcircuits, or motifs. These were incorporated into a neural architecture search approach to evolve network architectures. Second, we have conducted analysis of the heading direction circuit in the fruit fly, which performs fusion of visual and angular velocity features, to explore augmenting existing computational models with new insight. Our team discovered a novel pattern of connectivity, implemented a new model, and demonstrated sensor fusion on a robotic platform. Third, the team analyzed circuitry for memory formation in the fruit fly connectome, enabling the design of a novel generative replay approach. Finally, the team has begun analysis of connectivity in mammalian cortex to explore potential improvements to transformer networks. These constraints increased network robustness on the most challenging examples in the CIFAR-10-C computer vision robustness benchmark task, while reducing learnable attention parameters by over an order of magnitude. Taken together, these results demonstrate multiple potential approaches to utilize insight from neural systems for developing robust and efficient machine learning techniques.Comment: 11 pages, 4 figure

Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.

BACKGROUND: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda. METHODS AND FINDINGS: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045). CONCLUSION: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART

Predicting response to holistic breathlessness services: a pooled analysis of trial data

Background: Holistic breathlessness services have been developed for people with advanced disease and chronic breathlessness, leading to improved psychological aspects of breathlessness and health. The extent to which patient characteristics influence outcomes is unclear. Aim: To identify patient characteristics predicting outcomes of mastery and distress around breathlessness following holistic breathlessness services. Design: Secondary analysis of pooled individual patient data from three clinical trials. Our primary analysis assessed predictors of clinically important improvements in Chronic Respiratory Questionnaire mastery scores (+0.5 point), and our secondary analysis predictors of improvements in Numerical Rating Scale distress due to breathlessness (-1 point). Variables significantly related to improvement in univariate models were considered in separate backwards stepwise logistic regression models. Participants: The dataset comprised 259 participants (118 female; mean (standard deviation) age 69.2(10.6) years) with primary diagnoses of chronic obstructive pulmonary disease (49.8%), cancer (34.7%) and interstitial lung disease (10.4%).Results: Controlling for age, sex, and trial, baseline mastery remained the only significant independent predictor of improvement in mastery (odds ratio 0.57, 95% confidence intervals 0.43 to 0.74; p <0001), and baseline distress remained the only significant predictor of improvement in distress (odds ratio 1.64; 95% confidence intervals 1.35 to 2.03; p<001). Baseline lung function, breathlessness severity, health status, mild anxiety and depression, and diagnosis did not predict outcomes. Conclusions: Outcomes of mastery and distress following holistic breathlessness services are influenced by baseline scores for these variables, and not by diagnosis, lung function, or health status. Stratifying patients by levels of mastery and/or distress appears appropriate for clinical trials and services

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function