Mapping kinematic functional abilities of the hand to three dimensional shapes for inclusive design

Loss of hand function can have adverse effects on an individual\u27s ability to maintain independence. The ability to perform daily activities, such as food preparation and medication delivery, is dependent on the hand\u27s ability to grasp and manipulate objects. Therefore, the goal of this research was to demonstrate that three dimensional (3D) modeling of hand function can be used to improve the accessibility of handheld objects for individuals with reduced functionality through informed design. Individual models of hand functionality were created for 43 participants and group models were developed for groups of individuals without (Healthy) and with reduced functionality due to arthritis (RFA) of the hand. Cylindrical models representative of auto-injectors of varying diameters were analyzed in 3D space relative to hand function. The individual model mappings showed the cylinder diameter with the highest mapped functional values varied depending on the type of functional weighting chosen: kinematic redundancy of fingertip pad positional placement, fingertip pad orientation, or finger force directionality. The group mappings showed that for a cylinder to be grasped in a power grasp by at least 75% of the Healthy or RFA groups, a diameter of 40 mm was required. This research utilizes a new hand model to objectively compare design parameters across three different kinematic factors of hand function and across groups with different functional abilities. The ability to conduct these comparisons enables the creation of designs that are universal to all – including accommodation of individuals with limits in their functional abilities

Use of 1D Unsteady HEC-RAS in a Coupled System for Compound Flood Modeling: North Carolina Case Study

The research presented herein develops and compares an ADCIRC and ADCIRC/HEC-RAS (1D) paired model for the purpose of compound flood modeling within the Tar River and Pamlico Sound basins of North Carolina. Both the ADCIRC and 1D HEC-RAS models are capable of simulating river systems but differ in their underlying numerical formulations. A case-study comparison of each model’s ability to simulate flooding accurately and quickly in a riverine/estuarine system is investigated herein; results may serve as a valuable reference to forecasters and model developers. Individual models of the Tar River and Pamlico Sound area in North Carolina were used, and pairings of these models were devised to determine the benefits and drawbacks of using ADCIRC alone, or ADCIRC + 1D HEC-RAS, to simulate the response of the Tar River and Pamlico Sound during three test events: Hurricane Irene, Hurricane Floyd, and an unnamed April 2003 event. With increased emphasis on predicting total water levels, the results of this study can provide information for the possible development of similarly paired models for coastal river systems across the US and improve the body of knowledge about each model’s relative performance in riverine and estuarine areas.Ye

Metformin Blunts Muscle Hypertrophy in Response to Progressive Resistance Exercise Training in Older Adults: A Randomized, Double‐Blind, Placebo‐Controlled, Multicenter Trial: The MASTERS Trial

Progressive resistance exercise training (PRT) is the most effective known intervention for combating aging skeletal muscle atrophy. However, the hypertrophic response to PRT is variable, and this may be due to muscle inflammation susceptibility. Metformin reduces inflammation, so we hypothesized that metformin would augment the muscle response to PRT in healthy women and men aged 65 and older. In a randomized, double-blind trial, participants received 1,700 mg/day metformin (N = 46) or placebo (N = 48) throughout the study, and all subjects performed 14 weeks of supervised PRT. Although responses to PRT varied, placebo gained more lean body mass (p = .003) and thigh muscle mass (p \u3c .001) than metformin. CT scan showed that increases in thigh muscle area (p = .005) and density (p = .020) were greater in placebo versus metformin. There was a trend for blunted strength gains in metformin that did not reach statistical significance. Analyses of vastus lateralis muscle biopsies showed that metformin did not affect fiber hypertrophy, or increases in satellite cell or macrophage abundance with PRT. However, placebo had decreased type I fiber percentage while metformin did not (p = .007). Metformin led to an increase in AMPK signaling, and a trend for blunted increases in mTORC1 signaling in response to PRT. These results underscore the benefits of PRT in older adults, but metformin negatively impacts the hypertrophic response to resistance training in healthy older individuals. ClinicalTrials.gov Identifier: NCT02308228

Selectively targeting the kinome-conserved lysine of PI3K (delta) as a general approach to covalent kinase inhibition

Selective covalent inhibition of kinases by targeting poorly conserved cysteines has proven highly fruitful to date in the development of chemical probes and approved drugs. However, this approach is limited to ~200 kinases possessing such a cysteine near the ATP-binding pocket. Herein, we report a novel approach to achieve selective, irreversible kinase inhibition, by targeting the conserved catalytic lysine residue. We have illustrated our approach by developing selective, covalent PI3Kδ inhibitors that exhibit nanomolar potency in cellular assays, and a duration of action >48 h in CD4+ T cells. Despite conservation of the lysine residue throughout the kinome, the lead compound shows high levels of selectivity over a selection of lipid and protein kinases in biochemical assays, as well as covalent binding to very few off-target proteins in live-cell proteomic studies. We anticipate this approach could offer an alternative general strategy, to targeting non-conserved cysteines, for the development of selective covalent kinase inhibitors

Optimizing Provider Recruitment for Influenza Surveillance Networks

The increasingly complex and rapid transmission dynamics of many infectious diseases necessitates the use of new, more advanced methods for surveillance, early detection, and decision-making. Here, we demonstrate that a new method for optimizing surveillance networks can improve the quality of epidemiological information produced by typical provider-based networks. Using past surveillance and Internet search data, it determines the precise locations where providers should be enrolled. When applied to redesigning the provider-based, influenza-like-illness surveillance network (ILINet) for the state of Texas, the method identifies networks that are expected to significantly outperform the existing network with far fewer providers. This optimized network avoids informational redundancies and is thereby more effective than networks designed by conventional methods and a recently published algorithm based on maximizing population coverage. We show further that Google Flu Trends data, when incorporated into a network as a virtual provider, can enhance but not replace traditional surveillance methods

European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia

The diagnosis of primary ciliary dyskinesia is often confirmed with standard, albeit complex and expensive, tests. In many cases, however, the diagnosis remains difficult despite the array of sophisticated diagnostic tests. There is no "gold standard" reference test. Hence, a Task Force supported by the European Respiratory Society has developed this guideline to provide evidence-based recommendations on diagnostic testing, especially in light of new developments in such tests, and the need for robust diagnoses of patients who might enter randomised controlled trials of treatments. The guideline is based on pre-defined questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. It focuses on clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence. It then used a modified Delphi survey to develop an algorithm for the use of diagnostic tests to definitively confirm and exclude the diagnosis of primary ciliary dyskinesia; and to provide advice when the diagnosis was not conclusive. Finally, this guideline proposes a set of quality criteria for future research on the validity of diagnostic methods for primary ciliary dyskinesia

The Lunacy Commission.

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Governing Ecological Connectivity in Cross-Scale Dependent Systems.

Ecosystem management and governance of cross-scale dependent systems require integrating knowledge about ecological connectivity in its multiple forms and scales. Although scientists, managers, and policymakers are increasingly recognizing the importance of connectivity, governmental organizations may not be currently equipped to manage ecosystems with strong cross-boundary dependencies. Managing the different aspects of connectivity requires building social connectivity to increase the flow of information, as well as the capacity to coordinate planning, funding, and actions among both formal and informal governance bodies. We use estuaries in particular the San Francisco Estuary, in California, in the United States, as examples of cross-scale dependent systems affected by many intertwined aspects of connectivity. We describe the different types of estuarine connectivity observed in both natural and human-affected states and discuss the human dimensions of restoring beneficial physical and ecological processes. Finally, we provide recommendations for policy, practice, and research on how to restore functional connectivity to estuaries

Hemosporidian blood parasites in seabirds—a comparative genetic study of species from Antarctic to tropical habitats

Whereas some bird species are heavily affected by blood parasites in the wild, others reportedly are not. Seabirds, in particular, are often free from blood parasites, even in the presence of potential vectors. By means of polymerase chain reaction, we amplified a DNA fragment from the cytochrome b gene to detect parasites of the genera Plasmodium, Leucocytozoon, and Haemoproteus in 14 seabird species, ranging from Antarctica to the tropical Indian Ocean. We did not detect parasites in 11 of these species, including one Antarctic, four subantarctic, two temperate, and four tropical species. On the other hand, two subantarctic species, thin-billed prions Pachyptila belcheri and dolphin gulls Larus scoresbii, were found infected. One of 28 thin-billed prions had a Plasmodium infection whose DNA sequence was identical to lineage P22 of Plasmodium relictum, and one of 20 dolphin gulls was infected with a Haemoproteus lineage which appears phylogenetically clustered with parasites species isolated from passeriform birds such as Haemoproteus lanii, Haemoproteus magnus, Haemoproteus fringillae, Haemoproteus sylvae, Haemoproteus payevskyi, and Haemoproteus belopolskyi. In addition, we found a high parasite prevalence in a single tropical species, the Christmas Island frigatebird Fregata andrewsi, where 56% of sampled adults were infected with Haemoproteus. The latter formed a monophyletic group that includes a Haemoproteus line from Eastern Asian black-tailed gulls Larus crassirostris. Our results are in agreement with those showing that (a) seabirds are poor in hemosporidians and (b) latitude could be a determining factor to predict the presence of hemosporidians in birds. However, further studies should explore the relative importance of extrinsic and intrinsic factors on parasite prevalence, in particular using phylogenetically controlled comparative analyses, systematic sampling and screening of vectors, and within-species comparisons

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure