STORAGE UTILIZATION IN A DEFICIT REGION

Crop Production/Industries,

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

Genetic underpinnings of increased BMI and its association with late midlife cognitive abilities

OBJECTIVES: First, we test for differences in various cognitive abilities across trajectories of body mass index (BMI) over the later life course. Second, we examine whether genetic risk factors for unhealthy BMIs-assessed via polygenic risk scores (PRS)-predict cognitive abilities in late-life. METHODS: The study used a longitudinal sample of Vietnam veteran males to explore the associations between BMI trajectories, measured across four time points, and later cognitive abilities. The sample of 977 individuals was drawn from the Vietnam Era Twin Study of Aging. Cognitive abilities evaluated included executive function, abstract reasoning, episodic memory, processing speed, verbal fluency, and visual spatial ability. Multilevel linear regression models were used to estimate the associations between BMI trajectories and cognitive abilities. Then, BMI PRS was added to the models to evaluate polygenic associations with cognitive abilities. RESULTS: There were no significant differences in cognitive ability between any of the BMI trajectory groups. There was a significant inverse relationship between BMI-PRS and several cognitive ability measures. DISCUSSION: While no associations emerged for BMI trajectories and cognitive abilities at the phenotypic levels, BMI PRS measures did correlate with key cognitive domains. Our results suggest possible polygenic linkages cutting across key components of the central and peripheral nervous system.Published versio

Zaštitno djelovanje selenija protiv prekomjerne ekspresije apoptotskih gena povezanih s karcinomom u štakora izloženih o-krezolu

Cresols are monomethyl derivatives of phenol frequently used as solvents and intermediates in the production of disinfectants, fragrances, pesticides, dyes, and explosives, which is probably why they are widely distributed in the environment. General population may be exposed to cresols mainly through inhalation of contaminated air. In this study we evaluated the toxicological effects of o-cresol on differential gene expression profile of rat liver and prostate. Experiments were conducted on 80 male rats, 60 of which were exposed to o-cresol (1.5 g kg-1, 5 g kg-1, or 15 g kg-1) through feed for 8 weeks. Three groups of rats were supplemented with 0.1 mg kg-1 selenium (Se, in the form of, sodium selenite) in addition to o-cresol to evaluate its effectiveness against o-cresol toxicity. Control group received neither o-cresol nor Se, while one group received Se alone. Survival was similar between the exposed and control animals. Rats exposed to 15 g kg-1 of o-cresol showed a 16 % loss in body weight by the end of the study, which may have been related to o-cresol making feed unpalatable at this concentration. Liver and prostate tissue samples were collected at the end of the treatment. mRNA analysis revealed that apoptotic genes (CYP3A, COX-2, PPARγ, BAX, BCL2, AKT-1, and PKCα) related to cancer were up-regulated in liver and prostate tissues isolated from groups exposed to 5 g kg-1 and 15 g kg-1 o-cresol in comparison to control. Changes in gene expression profile were prevented when rats were supplemented with Se. The exact mechanisms underlying its protective effect remain to be clarified by future studies.Krezoli su monometilni derivati fenola koji se često rabe kao otapala te kao posrednici u proizvodnji dezinfekcijskih sredstava, mirisa, pesticida, boja i eksploziva. Otuda i njihova rasprostranjenost u okolišu. Opća je populacija izložena krezolima uglavnom putem zraka. U ovome se toksikološkom istraživanju ocijenilo djelovanje o-krezola, jednoga od tri krezolova izomera, na ekspresiju gena u tkivima jetre i prostate mužjaka štakora. Istraživanje je provedeno na 80 mužjaka, od kojih je 60 tijekom osam tjedana bilo izloženo o-krezolu (1,5 g kg-1, 5 g kg-1, odnosno 15 g kg-1) preko krmiva. Tri skupine štakora primale su uz o-krezol nadomjestak selenija u dozi od 0.1 mg kg-1 (Se, u obliku natrijeva selenita) radi ocjene njegove djelotvornosti protiv toksičnosti o-krezola. Kontrolna skupina nije primala ni o-krezol ni Se, dok je jedna skupina primala samo Se. Preživljenje je bilo podjednako u svih skupina životinja. Štakori izloženi najvišoj dozi o-krezola (15 g kg-1) imali su 16 % manju tjelesnu masu od kontrolne skupine na kraju ispitivanja, što može biti povezano s lošim okusom krmiva zbog primjese visoke doze o-krezola. S istekom osmotjednoga izlaganja o-krezolu životinje su eutanazirane te su prikupljeni uzorci tkiva jetre i prostate. Analiza m-RNA pokazala je značajno povišenu ekspresiju apoptotskih gena CYP3A, COX-2, PPARγ, BAX, BCL2, AKT-1 i PKCα, koji su povezani s nastankom karcinoma u skupinama štakora izloženim o-krezolu (5 g kg-1 i 15 g kg-1 u odnosu na kontrolu. Ova je prekomjerna ekspresija poništena u štakora koji su primali selenij. Još nisu jasni mehanizmi iza ovoga zaštitnog djelovanja, na što će odgovoriti buduća istraživanja

Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis

Despite the substantial heritability of antisocial behavior (ASB), specific genetic variants robustly associated with the trait have not been identified. The present study by the Broad Antisocial Behavior Consortium (BroadABC) meta-analyzed data from 28 discovery samples (N = 85,359) and five independent replication samples (N = 8058) with genotypic data and broad measures of ASB. We identified the first significant genetic associations with broad ASB, involving common intronic variants in the forkhead box protein P2 (FOXP2) gene (lead SNP rs12536335, p = 6.32 × 10−10). Furthermore, we observed intronic variation in Foxp2 and one of its targets (Cntnap2) distinguishing a mouse model of pathological aggression (BALB/cJ strain) from controls (BALB/cByJ strain). Polygenic risk score (PRS) analyses in independent samples revealed that the genetic risk for ASB was associated with several antisocial outcomes across the lifespan, including diagnosis of conduct disorder, official criminal convictions, and trajectories of antisocial development. We found substantial genetic correlations of ASB with mental health (depression rg = 0.63, insomnia rg = 0.47), physical health (overweight rg = 0.19, waist-to-hip ratio rg = 0.32), smoking (rg = 0.54), cognitive ability (intelligence rg = −0.40), educational attainment (years of schooling rg = −0.46) and reproductive traits (age at first birth rg = −0.58, father’s age at death rg = −0.54). Our findings provide a starting point toward identifying critical biosocial risk mechanisms for the development of ASB

Investigation of the Performance of the New Orleans Flood Protection System in Hurricane Katrina on August 29, 2005: Volume 1

This report presents the results of an investigation of the performance of the New Orleans regional flood protection system during and after Hurricane Katrina, which struck the New Orleans region on August 29, 2005. This event resulted in the single most costly catastrophic failure of an engineered system in history. Current damage estimates at the time of this writing are on the order of $100 to$200 billion in the greater New Orleans area, and the official death count in New Orleans and southern Louisiana at the time of this writing stands at 1,293, with an additional 306 deaths in nearby southern Mississippi. An additional approximately 300 people are currently still listed as “missing”; it is expected that some of these missing were temporarily lost in the shuffle of the regional evacuation, but some of these are expected to have been carried out into the swamps and the Gulf of Mexico by the storm’s floodwaters, and some are expected to be recovered in the ongoing sifting through the debris of wrecked homes and businesses, so the current overall regional death count of 1,599 is expected to continue to rise a bit further. More than 450,000 people were initially displaced by this catastrophe, and at the time of this writing more than 200,000 residents of the greater New Orleans metropolitan area continue to be displaced from their homes by the floodwater damages from this storm event. This investigation has targeted three main questions as follow: (1) What happened?, (2) Why?, and (3) What types of changes are necessary to prevent recurrence of a disaster of this scale again in the future? To address these questions, this investigation has involved: (1) an initial field reconnaissance, forensic study and data gathering effort performed quickly after the arrival of Hurricanes Katrina (August 29, 2005) and Rita (September 24, 2005), (2) a review of the history of the regional flood protection system and its development, (3) a review of the challenging regional geology, (4) detailed studies of the events during Hurricanes Katrina and Rita, as well as the causes and mechanisms of the principal failures, (4) studies of the organizational and institutional issues affecting the performance of the flood protection system, (5) observations regarding the emergency repair and ongoing interim levee reconstruction efforts, and (6) development of findings and preliminary recommendations regarding changes that appear warranted in order to prevent recurrence of this type of catastrophe in the future. In the end, it is concluded that many things went wrong with the New Orleans flood protection system during Hurricane Katrina, and that the resulting catastrophe had it roots in three main causes: (1) a major natural disaster (the Hurricane itself), (2) the poor performance of the flood protection system, due to localized engineering failures, questionable judgments, errors, etc. involved in the detailed design, construction, operation and maintenance of the system, and (3) more global “organizational” and institutional problems associated with the governmental and local organizations responsible for the design, construction, operation, maintenance and funding of the overall flood protection system

Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression

Risk-taking behaviour is an important component of several psychiatric disorders, including attention-deficit hyperactivity disorder, schizophrenia and bipolar disorder. Previously, two genetic loci have been associated with self-reported risk taking and significant genetic overlap with psychiatric disorders was identified within a subsample of UK Biobank. Using the white British participants of the full UK Biobank cohort (n = 83,677 risk takers versus 244,662 controls) for our primary analysis, we conducted a genome-wide association study of self-reported risk-taking behaviour. In secondary analyses, we assessed sex-specific effects, trans-ethnic heterogeneity and genetic overlap with psychiatric traits. We also investigated the impact of risk-taking-associated SNPs on both gene expression and structural brain imaging. We identified 10 independent loci for risk-taking behaviour, of which eight were novel and two replicated previous findings. In addition, we found two further sex-specific risk-taking loci. There were strong positive genetic correlations between risk-taking and attention-deficit hyperactivity disorder, bipolar disorder and schizophrenia. Index genetic variants demonstrated effects generally consistent with the discovery analysis in individuals of non-British White, South Asian, African-Caribbean or mixed ethnicity. Polygenic risk scores comprising alleles associated with increased risk taking were associated with lower white matter integrity. Genotype-specific expression pattern analyses highlighted DPYSL5, CGREF1 and C15orf59 as plausible candidate genes. Overall, our findings substantially advance our understanding of the biology of risk-taking behaviour, including the possibility of sex-specific contributions, and reveal consistency across ethnicities. We further highlight several putative novel candidate genes, which may mediate these genetic effects

Highly Sensitive and Specific Detection of Rare Variants in Mixed Viral Populations from Massively Parallel Sequence Data

Viruses diversify over time within hosts, often undercutting the effectiveness of host defenses and therapeutic interventions. To design successful vaccines and therapeutics, it is critical to better understand viral diversification, including comprehensively characterizing the genetic variants in viral intra-host populations and modeling changes from transmission through the course of infection. Massively parallel sequencing technologies can overcome the cost constraints of older sequencing methods and obtain the high sequence coverage needed to detect rare genetic variants (<1%) within an infected host, and to assay variants without prior knowledge. Critical to interpreting deep sequence data sets is the ability to distinguish biological variants from process errors with high sensitivity and specificity. To address this challenge, we describe V-Phaser, an algorithm able to recognize rare biological variants in mixed populations. V-Phaser uses covariation (i.e. phasing) between observed variants to increase sensitivity and an expectation maximization algorithm that iteratively recalibrates base quality scores to increase specificity. Overall, V-Phaser achieved >97% sensitivity and >97% specificity on control read sets. On data derived from a patient after four years of HIV-1 infection, V-Phaser detected 2,015 variants across the ∼10 kb genome, including 603 rare variants (<1% frequency) detected only using phase information. V-Phaser identified variants at frequencies down to 0.2%, comparable to the detection threshold of allele-specific PCR, a method that requires prior knowledge of the variants. The high sensitivity and specificity of V-Phaser enables identifying and tracking changes in low frequency variants in mixed populations such as RNA viruses

Transduction of SIV-Specific TCR Genes into Rhesus Macaque CD8+ T Cells Conveys the Ability to Suppress SIV Replication

The SIV/rhesus macaque model for HIV/AIDS is a powerful system for examining the contribution of T cells in the control of AIDS viruses. To better our understanding of CD8(+) T-cell control of SIV replication in CD4(+) T cells, we asked whether TCRs isolated from rhesus macaque CD8(+) T-cell clones that exhibited varying abilities to suppress SIV replication could convey their suppressive properties to CD8(+) T cells obtained from an uninfected/unvaccinated animal.We transferred SIV-specific TCR genes isolated from rhesus macaque CD8(+) T-cell clones with varying abilities to suppress SIV replication in vitro into CD8(+) T cells obtained from an uninfected animal by retroviral transduction. After sorting and expansion, transduced CD8(+) T-cell lines were obtained that specifically bound their cognate SIV tetramer. These cell lines displayed appropriate effector function and specificity, expressing intracellular IFNγ upon peptide stimulation. Importantly, the SIV suppression properties of the transduced cell lines mirrored those of the original TCR donor clones: cell lines expressing TCRs transferred from highly suppressive clones effectively reduced wild-type SIV replication, while expression of a non-suppressing TCR failed to reduce the spread of virus. However, all TCRs were able to suppress the replication of an SIV mutant that did not downregulate MHC-I, recapitulating the properties of their donor clones.Our results show that antigen-specific SIV suppression can be transferred between allogenic T cells simply by TCR gene transfer. This advance provides a platform for examining the contributions of TCRs versus the intrinsic effector characteristics of T-cell clones in virus suppression. Additionally, this approach can be applied to develop non-human primate models to evaluate adoptive T-cell transfer therapy for AIDS and other diseases