An electrophysiological investigation of spontaneous and evoked activity in the lateral geniculate nucleus of unanaesthetized, anaesthetized and blinded cats.

Many studies have been done in an attempt to establish the structural and functional properties of the various sensory systems in the body. In particular, there have been many reports of experiments carried out on the visual systems of various vertebrates. (For a recent review of much of the literature see Creutzfeldt and Sakmann, 1969). This thesis describes the results of some experiments on the visual system of unanaesthetized and anaesthetized cats

Virtual World Problem-Centered Challenge Evaluation

This paper describes the two-year implementation evaluation of a problem-based engineering design challenge held in a virtual world. The team-based challenge was designed and facilitated by an aerospace research and education institute for middle and high school student competitors in both classrooms and afterschool programs across the U.S. An independent evaluation team examined participant experiences to consider the strengths of the challenge, as well as recommendations to enhance the effectiveness and efficiency of future challenges. Overall, the evaluation team found that the problem-centered design challenge offered the student competitors a unique and valuable opportunity to engage in real-life science and engineering problems with the support of advanced science, technology, and engineering resources and college-level and professional experts. Recommendations centered on needed adjustments to achieve and prepare for growth, support for teams, assessment refinement, and collaboration and other technology enhancement

Wide Angle Decentered Lens Beam Steering for Infrared Countermeasures Applications

A beam-steering system consisting of three cemented achromatic doublets is presented. Intended for use in IR countermeasure applications, our system is designed to operate over the 2- to 5-μm spectrum with minimum angular dispersion. We show that dispersion can be minimized by using doublet lenses fashioned from AMTIR-1 and germanium. Our system is designed to be compact and lightweight, with no internal foci, while allowing steering to ±22.5 deg. We also maintain a minimum 2-in. clear aperture for all steering angles, and a nominal divergence of 1 mrad. Plane wave and Gaussian beam analyses of our system are presented

Strength of Plantar- and Dorsiflexors Mediates Step Regularity During a High Cognitive Load Situation in a Cross-sectional Cohort of Older and Younger Adults

Background and Purpose: Completing simultaneous tasks while standing or walking (ie, a high cognitive load situation [HCLS]) is inevitable in daily activities and can lead to interference in task performances. Age-related physical and cognitive changes may confound performance variability during HCLS in older and younger adults. Identification of these confounding effects may reveal therapy targets to maintain optimal physical function later in life. The aim of this study was to investigate the effect of increasing the difficulty levels of an additional motor task and restricting visual information, on gait parameters in younger and older adults while considering the effect of cognitive and physical covariates. Methods: Fifteen healthy younger and 14 healthy older adults were asked to complete assessments of cognitive function, balance, and strength. They were then asked to walk on a self-paced treadmill with or without carrying a plastic tray. Opaqueness of the tray (vision) and the presence of water in glasses placed on the tray (increasing task difficulty) were varied. Mean, standard deviation, and regularity (sample entropy) of step width and length were compared across conditions and groups using repeated-measures analyses of variance with and without covariate analysis. Only significantly correlated covariates of cognition, balance, and strength were entered into each model. Results and Discussion: Older adults had greater step width irregularity compared with younger adults across all conditions when controlling for concentric plantar- and dorsiflexion strength. A decline in strength may likely alter neuromuscular control of gait, specifically control of step width, which has been associated with fall risk in older adults. Adjusting for the same covariates revealed increased regularity of step length, as visual feedback from the feet was restricted. Specifically, step length was more regular while carrying an opaque tray compared with not carrying a tray. Visual restriction was a contributing factor, which led to more predictable gait kinematics, indicating the role of sensory information to enhance the adaptability during walking under HCLS. Conclusion: The knowledge of the regularity behavior of human movement can expand physical therapists\u27 treatment approaches to promote further interactivity and coordination across body systems that model behavior of healthy young individuals. Targeting strength during therapy may provide additional benefits for gait performance under HCLS

Microbiome‑driven breeding strategy potentially improves beef fatty acid profile benefiting human health and reduces methane emissions

BACKGROUND: Healthier ruminant products can be achieved by adequate manipulation of the rumen microbiota to increase the flux of beneficial fatty acids reaching host tissues. Genomic selection to modify the microbiome function provides a permanent and accumulative solution, which may have also favourable consequences in other traits of interest (e.g. methane emissions). Possibly due to a lack of data, this strategy has never been explored. RESULTS: This study provides a comprehensive identification of ruminal microbial mechanisms under host genomic influence that directly or indirectly affect the content of unsaturated fatty acids in beef associated with human dietary health benefits C18:3n-3, C20:5n-3, C22:5n-3, C22:6n-3 or cis-9, trans-11 C18:2 and trans-11 C18:1 in relation to hypercholesterolemic saturated fatty acids C12:0, C14:0 and C16:0, referred to as N3 and CLA indices. We first identified that ~27.6% (1002/3633) of the functional core additive log-ratio transformed microbial gene abundances (alr-MG) in the rumen were at least moderately host-genomically influenced (HGFC). Of these, 372 alr-MG were host-genomically correlated with the N3 index (n=290), CLA index (n=66) or with both (n=16), indicating that the HGFC influence on beef fatty acid composition is much more complex than the direct regulation of microbial lipolysis and biohydrogenation of dietary lipids and that N3 index variation is more strongly subjected to variations in the HGFC than CLA. Of these 372 alr-MG, 110 were correlated with the N3 and/or CLA index in the same direction, suggesting the opportunity for enhancement of both indices simultaneously through a microbiome-driven breeding strategy. These microbial genes were involved in microbial protein synthesis (aroF and serA), carbohydrate metabolism and transport (galT, msmX), lipopolysaccharide biosynthesis (kdsA, lpxD, lpxB), or flagellar synthesis (flgB, fliN) in certain genera within the Proteobacteria phyla (e.g. Serratia, Aeromonas). A microbiome-driven breeding strategy based on these microbial mechanisms as sole information criteria resulted in a positive selection response for both indices (1.36±0.24 and 0.79±0.21 sd of N3 and CLA indices, at 2.06 selection intensity). When evaluating the impact of our microbiome-driven breeding strategy to increase N3 and CLA indices on the environmental trait methane emissions (g/kg of dry matter intake), we obtained a correlated mitigation response of −0.41±0.12 sd. CONCLUSION: This research provides insight on the possibility of using the ruminal functional microbiome as information for host genomic selection, which could simultaneously improve several microbiome-driven traits of interest, in this study exemplified with meat quality traits and methane emissions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40168-022-01352-6

Pursuing High Performance in Rural Health Care

In 2001, the Institute of Medicine (IOM) called for transformation of the United States health care system to make it safe, effective, patient-centered, timely, efficient, and equitable.1 The journey toward these six aims in public policy and the private sector is underway, but fundamental challenges detailed by the IOM remain. Patients are injured at alarming rates, wide variation in care exists across geographies, patients complain of insensitive and/or inaccessible health care providers, health care costs are nearly twice that in other developed countries, and nearly 50 million Americans lack health insurance. As a result, our health care is often fragmented, uncoordinated, and excessively costly. In fact, the United States health care system has been called a “non-system.” The rural health care landscape is additionally challenged by independent and autonomous providers often struggling to survive financially, burdensome geographic separations in health care services, and incompatible information technologies. As a result, resources are wasted, patients are harmed, and rural communities are neglected. Despite persistent rural challenges, public policies during the past 30 years have helped build and stabilize rural health care services. New payments have increased revenue for physicians practicing in shortage areas, rural hospitals certified as Critical Access Hospitals (very small hospitals in isolated places), Sole Community Hospitals (larger hospitals also in isolated areas), and Rural Health Clinics (primary care clinics staffed by nurse practitioners and/or physician assistants). New programs continue to provide technical assistance and grants to rural hospitals (Medicare Rural Hospital Flexibility Program), fund installation of telemedicine equipment, and promote rural health professions education. These successes have required political capital and developmental resources to support a system that delivers discrete and uncoordinated health care services, provided by specific professionals and institutions, each paid on a per-service basis. Yet, progressive work by the Institute of Medicine (especially the Rural Health Committee document Quality Through Collaboration: The Future of Rural Health Care), the Commonwealth Commission on a High Performance Healthcare System, and other organizations suggest more effective strategies to improve and sustain the health of rural people..

Sublethal concentrations of 17-AAG suppress homologous recombination DNA repair and enhance sensitivity to carboplatin and olaparib in HR proficient ovarian cancer cells

The promise of PARP-inhibitors(PARPis) in the management of epithelial ovarian cancer(EOC) is tempered by the fact that approximately 50% of patients with homologous recombination (HR)-proficient tumors do not respond well to these agents. Combination of PARPis with agents that inhibit HR may represent an effective strategy to enhance their activity in HR-proficient tumors. Using a bioinformatics approach, we identified that heat shock protein 90 inhibitors(HSP90i) may suppress HR and thus revert HR-proficient to HR-deficient tumors. Analysis of publicly available gene expression data showed that exposure of HR-proficient breast cancer cell lines to HSP90i 17-AAG(17-allylamino-17-demethoxygeldanamycin) downregulated HR, ATM and Fanconi Anemia pathways. In HR-proficient EOC cells, 17-AAG suppressed HR as assessed using the RAD51 foci formation assay and this was further confirmed using the Direct Repeat-GFP reporter assay. Furthermore, 17-AAG downregulated BRCA1 and/or RAD51 protein levels, and induced significantly more γH2AX activation in combination with olaparib compared to olaparib alone. Finally, sublethal concentrations of 17-AAG sensitized HR-proficient EOC lines to olaparib and carboplatin but did not affect sensitivity of the HR-deficient OVCAR8 line arguing that the 17-AAG mediated sensitization is dependent on suppression of HR. These results provide a preclinical rationale for using a combination of olaparib/17-AAG in HR-proficient EOC

Translational neurophysiology in sheep:Measuring sleep and neurological dysfunction in CLN5 affected Batten disease sheep

This is the final published version of a paper originally published in BRAIN 2015: 138; 862?874, DOI: http://dx.doi.org/10.1093/brain/awv026Creating valid mouse models of slowly progressing human neurological diseases is challenging, not least because the short lifespan of rodents confounds realistic modelling of disease time course. With their large brains and long lives, sheep offer significant advantages for translational studies of human disease. Here we used normal and CLN5 Batten disease affected sheep to demonstrate the use of the species for studying neurological function in a model of human disease. We show that electroencephalography can be used in sheep, and that longitudinal recordings spanning many months are possible. This is the first time such an electroencephalography study has been performed in sheep. We characterized sleep in sheep, quantifying characteristic vigilance states and neurophysiological hallmarks such as sleep spindles. Mild sleep abnormalities and abnormal epileptiform waveforms were found in the electroencephalographies of Batten disease affected sheep. These abnormalities resemble the epileptiform activity seen in children with Batten disease and demonstrate the translational relevance of both the technique and the model. Given that both spontaneous and engineered sheep models of human neurodegenerative diseases already exist, sheep constitute a powerful species in which longitudinal in vivo studies can be conducted. This will advance our understanding of normal brain function and improve our capacity for translational research into neurological disorders.This work was funded by CHDI Inc. (AJM). Founding the\ud sheep flock, and costs in NZ relating to the rearing and\ud genotyping of the animals were funded by a series of grants\ud from the Neurological Foundation of NZ and the Batten\ud Disease Support and Research Association (DNP, NLM)