Search

Peptide deformylase (PDF) is involved in bacterial protein maturation processes. Originating from the interest in a new antibiotic, tremendous effort was put into the refinement of PDF inhibitors (PDFIs) and their selectivity. We obtained a full NMR backbone assignment the emergent additional protein backbone resonances of ecPDF 1-147 in complex with 2-(5-bromo-1H-indol-3-yl)-N-hydroxyacetamide (2), a potential new structural scaffold for more selective PDFIs. We also determined the complex crystal structures of E. coliPDF (ecPDF fl) and 2. Our structure suggests an alternative ligand conformation within the protein, a possible starting point for further selectivity optimization. The orientation of the second ligand conformation in the crystal structure points toward a small region of the S1' pocket, which differs between bacterial PDFs and human PDF. Moreover, we analyzed the binding mode of 2via NMR TITAN line shape analysis, revealing an induced fit mechanism.

We report on a 53-year-old female patient and a 33-year-old male patient presenting with life-threatening hypercalcemic crisis caused by self-induced vitamin-D intoxication. Both patients took high doses of vitamin D3supplements, cumulatively up to 2,500,000–10,000,000 I.U. over several months. Accordingly, serum 25-OH-vitamin D concentrations were increased to 663 and 1289 nmol/L (reference 50–175 nmol/L), respectively. As forced diuresis and bisphosphonates failed to correct recurrent hypercalcemia, we hypothesized that add-on extracorporeal treatments might help overcome the refractory situation. Considering the binding of vitamin D3metabolites to vitamin D-binding protein (VDBP, 59 kDa), we started extracorporeal treatments involving total plasma exchange with replacement by human albumin and by fresh frozen plasma, online hemodiafiltration and high cut-off hemodialysis. We found that in the former case, total plasma exchange with albumin and fresh frozen plasma and high cut-off hemodialysis lowered both 25-OH-vitamin D3and 1,25-OH-vitamin D3,whereas in the latter case total plasma exchange with albumin was found to more effectively remove vitamin D metabolites compared to high cut-off hemodialysis. In contrast, the amount of total plasma calcium removed by high cut-off hemodialysis was higher compared to total plasma exchange with albumin. During follow up, patients 1 and 2 achieved almost normal total plasma calcium and vitamin D concentrations after 355 and 109 days, respectively. These two cases suggest that extracorporeal treatments with high cut-off hemodialysis and total plasma exchange with albumin may be considered as add-on treatment in refractory cases of vitamin D3-induced hypercalcemia to lower plasma 25-OH-vitamin D3concentrations.

ABSTRACTCurrently, there is no non-anthropocentric guide to the practice of nature conservation and the treatment of invasive species and domestic animals. In examining the so-called ‘ecocentric’ and ‘animal’ ethics, we highlight some differences between them, and argue that the basic aspiration for support of all nonhuman life needs to be retained. We maintain that hierarchies of value need to be flexible, establishing basic principles and then weighing up the options in the context of anthropocentrism, industrial development and human population growth. Acknowledging the role of these conditions creates space for combining individual-based and collective-based ethics in practice.

Acute allograft injury was observed in a 37-year-old woman within a few weeks after kidney transplantation. Neither renal ultrasound nor computerized tomography (CT) and magnetic resonance (MR) angiography revealed any anomaly. An MR protocol was then performed including arterial spin labeling and intravoxel incoherent motion diffusion weighted imaging. Both arterial spin labeling and the perfusion fraction in the diffusion weighted imaging showed decreased perfusion compared to reference values. The patient subsequently underwent angiography, where an arteriovenous fistula in the upper calix of the transplant kidney was detected and immediate embolization was performed. A second functional MR, performed one week later, demonstrated a 40% increase in organ perfusion. We conclude that functional MR with arterial spin labeling and intravoxel incoherent motion have the potential to provide complementary information of clinical value to conventional imaging for monitoring renal allografts.

The ethical aspects of the design of executive compensation packages are discussed. The methods of designing equitable comepensation packages for executives are described.

O'Brien, Kevin J. Violence of climate change: lessons of resistance from nonviolent activists. Georgetown University, 2017. 228p bibl index ISBN 9781626164345 cloth, $49.95; ISBN 9781626164352 pbk, $24.95; ISBN 9781626164369 ebook, [...]

Investigations into fraud and abuse in Medicare can be improved with information technology. The Balanced Budget Act of 1997 included $16.2 bil in budget cuts for Medicare, and Operation Restore Trust has been developed to save these funds through identifying nearly $188 mil owed to the federal government between 1995 and 1997. Information technology can provide an accurate record of coding and billing practices and medical verification necessary to reduce fraud and abuse., "Fraud and abuse" is the name applied to any practice that misrepresents the activities of a health care organization in terms of billing, reporting, or reimbursement for services and that [...]

Gardiner, L. S. Tales from an uncertain world: what other assorted disasters can teach us about climate change. Iowa, 2018. 183p bibl index ISBN 9781609385538 pbk, $19.95; ISBN 9781609385545 ebook, [...]

„Wide awake local anesthesia no tourniquet“ (WALANT) bezeichnet ein blutungs- und komplikationsarmes Lokalanästhesieverfahren, das Handeingriffe am wachen Patienten ohne den Einsatz einer Blutsperre ermöglicht. Dies wird durch den Zusatz vasokonstriktiver Substanzen in der Infiltrationslösung möglich. Da die Motorik der Extremität nicht beeinflusst wird, bietet es zusätzlich die Möglichkeit der intraoperativen aktiven Funktionsprüfung. Die WALANT-Anästhesie ist ein etabliertes, effektives, leicht erlernbares und Ressourcen schonendes Verfahren. Das Spektrum der chirurgischen Möglichkeiten mit WALANT ist breit und deckt nahezu alle elektiven und viele notfallbedingten Eingriffe ab. Aufgrund mannigfaltiger Vorteile gegenüber allgemeinen Anästhesieverfahren findet WALANT in der Chirurgie immer neue Indikationen und Anwender. Es ist daher für die handchirurgische Versorgung im klinischen wie im niedergelassenen Bereich gleichermaßen interessant.

Rotating detonation engines (RDEs) are the subject of research in the combustion community due to the prospects of enhanced thermal efficiency and power density when compared to current deflagrative-based aerospace combustors. Many current simulations presume premixed reactants and therefore miss the important characteristics of transient mixing, wave-induced mixing, and injector design/spacing that are known to play a pivotal role in the system performance. Very ambitious large eddy simulations are being conducted, but necessarily on a limited number of realistic and complex cases, thus limiting their utility in deriving fundamental understanding. For these reasons, a two dimensional parametric study was conducted to assess propagation of a detonation across an idealized array of mixing/injection sites, parametrically characterized by the width and axial mixing profile.

(cc) 55-1730 QH45 CIP Keim, Brandon. The eye of the sandpiper: stories from the living world. Comstock Publishing Associates, 2017. 251 p bibl index ISBN 9781501707728 pbk, $19.95; ISBN 9781501712654 [...]

Decision-support and data warehousing software tools can help to increase competitive advantage in a health care system. Such tools can be helpful in the areas of management of capitation, revenue, cost and profitability; clinical resources; operations; outcomes; and population. Decision makers need the right information at the right time to bring about the right process changes. Decision support systems (DSSs) offer tools to enable health care users to analyze and distribute information needed to perform daily tasks and stay ahead of competition., Today's evolving health care environment requires improvements in how information is processed, distributed, analyzed, and used. As health care organizations begin to operate with increased fiscal responsibility, executives need direct [...]

Use of information technology in health care in the 1990s has brought about tremendous choices to the consumer. The power of sharing data by using communication systems as a tool between doctors and patients is growing. Leadership must bring together organizational vision and a mission of common focus., The computer is the dominant metaphor of our age; it defines our era by suggesting a new relationship to work, to power, and to nature itself. That relationship can best [...]

Peh, Kelvin S.-H. Routledge handbook of forest ecology, by Kelvin S.-H.Peh, Richard T.Corlett and Yves Bergeron. Routledge, 2015. 652p bibl index ISBN 9780415735452 cloth, $220.00; ISBN 9781315818290 ebook, contact publisher [...]

Background:Although renal replacement therapy prevents death from uremia, survival among patients with acute and chronic kidney diseases (CKD) remains an imperative concern. The expected life span of US dialysis patients 60–64 years of age is approximately 4.5 years; this is similar to that of patients with lung cancer. Despite substantial progress in many medical specialties over the past decades (e.g., notable reductions in myocardial infarction, stroke, and mortality rates in the general population), survival among dialysis patients has not improved significantly over the same period. A few decades ago, HIV infection and AIDS were pretty much a death sentence. Because of progress in HIV treatment, now it can be controlled with a daily pill, and ongoing research is pushing treatment even further and controls the virus with longer-acting treatment. A cure is no longer impossible for HIV and other viral infections such as hepatitis B and C and many malignancies, but so far there is no cure for CKD. Summary:Billions of dollars have been spent on kidney disease research in the past decades, with no tangible progress in clinical practice. The challenges of improving the quantity and quality of trials in nephrology are enormous. The number of randomized controlled trials (RCTs) published in nephrology is lower than that in other medical subspecialties, and most of the big RCTs in nephrology yield negative results. Nephrology studies evaluating hard clinical endpoints or surrogate endpoints are scarce. Key Message:Herein we discuss the slow progress in nephrology research that has impacted clinical practice over the last couple of decades and highlight the major obstacles, challenges, and potential solutions.

Mantle convection models based on geophysical constraints have provided us with a basic understanding of the forces driving and resisting plate motions on Earth. However, existing studies computing the balance of underlying forces are contradicting, and the impact of plate boundary geometry on surface deformation remains unknown. We address these issues by developing global instantaneous 3‐D mantle convection models with a heterogeneous density and viscosity distribution and weak plate boundaries prescribed using different geometries. We find that the plate boundary geometry of the Global Earthquake Model (GEM, Pagani et al., 2018, https://doi.org/10.1177/8755293020931866), featuring open plate boundaries with discrete lithospheric‐depth weak zones in the oceans and distributed crustal faults within continents, achieves the best fit to the observed GPS data with a directional correlation of 95.1% and a global point‐wise velocity residual of 1.87 cm/year. A good fit also requires plate boundaries being 3 to 4 orders of magnitude weaker than the surrounding lithosphere and low asthenospheric viscosities between 5 × 1017and 5 × 1018Pa s. Models without asthenospheric and lower mantle heterogeneities retain on average 30% and 70% of the plate speeds, respectively. Our results show that Earth's plate boundaries are not uniform and better described by more discrete plate boundaries within the oceans and distributed faults within continents. Furthermore, they emphasize the impact of plate boundary geometry on the direction and speed of plate motions and reaffirm the importance of slab pull in the uppermost mantle as a major plate driving force. Plate tectonics can explain several geological and geophysical phenomena on Earth and is closely coupled to convection in the underlying mantle. To understand this plate–mantle coupling and quantify the forces contributing to plate motion, we develop high‐resolution three‐dimensional computational models of the Earth's present‐day mantle flow utilizing available geophysical constraints on density distribution and rheology. Additionally, we prescribe weak zones at the location of plate boundaries. We use different plate boundary geometries, forming either open or closed polygons, and we vary how easily the plate boundaries and the asthenosphere directly below the plates can be deformed to determine which model best fits observed plate motions. Our best‐fitting model features open plate boundaries that are weak (∼4 orders of magnitude weaker than the surrounding lithosphere) and traverse the whole plate in the oceans, but are shallower and more distributed within continents. The asthenosphere in these models is even weaker than the plate boundaries. Furthermore, we find that the downward force caused by subducted slabs contributes the most to the observed surface velocities. Our models suggest that plate boundaries are not uniformly weak everywhere and that their geometry has a strong influence on the direction and speed of plate motion. We model plate motions in global instantaneous 3‐D mantle convection models with different plate boundary geometriesEarth's plate boundaries are not uniform and better described by discrete shear zones in the oceans and distributed faults within continentsSlab pull within the uppermost mantle (<300 km depth) contributes about 70% of the total plate driving force We model plate motions in global instantaneous 3‐D mantle convection models with different plate boundary geometries Earth's plate boundaries are not uniform and better described by discrete shear zones in the oceans and distributed faults within continents Slab pull within the uppermost mantle (<300 km depth) contributes about 70% of the total plate driving force

DISEASE MANAGEMENT is a concept that has been floating around the health care industry for nearly a decade. When first introduced by pharmaceutical companies in the early 1990s, disease management [...]

A LITTLE MORE than a year ago in this column I wrote about why organizations should adopt Internet technology to enhance their marketing and educational activities, as well as improve [...]

NOW THAT the dust has settled somewhat on Y2K and we can turn our attention back to matters shelved in its anticipation, another broad and consequential set of issues looms [...]

UNFORTUNATELY for most organizations, Y2K preparations took more time, effort, and resources than expected. As a result, many key information technology (IT) projects were shelved or waylaid, at least for [...]

An evaluation is presented regarding the automated dispensing of drugs to avoid medication errors. Automation is favored for ensuring that specific conditions are met in drug dispensing, such as correct dosages at the right time to the proper patients., EACH YEAR therapeutic drug use kills as many as i98,815 people, places 8.8 more in hospitals, accounts for 28% of all hospital admissions, and costs as much as $182 billion [...]

CONSUMER AND PURCHASER concerns about health care quality have escalated dramatically. Both public and private payers are demanding data to support claims of quality. Accrediting and regulatory agencies have responded [...]

Ferguson, Cody. This is our land: grassroots environmentalism in the late twentieth century. Rutgers, 2015. 223p bibl index afp ISBN 9780813565637 cloth, $90.00; ISBN 9780813565620 pbk, $28.95; ISBN 9780813575612 ebook, [...]

I am compelled to comment on John Gratto's My View column 'Addressing Incivility in a Civil Manner' (August 2015). His advice to focus on building relationships while under attack is [...]

Harris, Amanda. Fruits of Eden: David Fairchild and America's plant hunters. University Press of Florida, 2015. 303p bibl index afp ISBN 9780813060613 cloth, $24.95 (CC) 53-1280 Orig Journalist Harris has [...]

50-4410 QL63 2011-45700 CIP Poliquin, Rachel. The breathless zoo: taxidermy and the cultures of longing. Pennsylvania State, 2012. 259p index ISBN 0271053720, $34.95; ISBN 9780271053721, $34.95 The Breathless Zoo is [...]

Kemmerer, Lisa. Eating earth: environmental ethics and dietary choice. Oxford, 2015. 147p bibl index ISBN 9780199391844 cloth, $29.95 52-5297 TD195 2014-14219 MARC Kemmerer (Montana State Univ., Billings) is a philosopher, [...]

47-0860 SD565 MARC Hays, Samuel P. The American people & the national forests: the first century of the U. S. Forest Service. Pittsburgh, 2009. 198p bibl index afp ISBN 9780822943693, [...]

Miller, Char. Seeking the greatest good: the conservation legacy of Gifford Pinchot. Pittsburgh, 2013. 220p index afp ISBN 9780822962670 pbk, $24.95 51-6738 QH76 2013-23785 CIP This is not meant to [...]

Dyslexia is a common specific learning disability with a substantive genetic component. Several candidate genes have been proposed to be implicated in dyslexia susceptibility, such as DYX1C1, ROBO1, KIAA0319, and DCDC2. Associations with variants in these genes have also been reported with a variety of psychometric measures tapping into the underlying processes that might be impaired in dyslexic people. In this study, we first conducted a literature review to select single nucleotide polymorphisms (SNPs) in dyslexia candidate genes that had been repeatedly implicated across studies. We then assessed the SNPs for association in the richly phenotyped longitudinal data set from the Dutch Dyslexia Program. We tested for association with several quantitative traits, including word and nonword reading fluency, rapid naming, phoneme deletion, and nonword repetition. In this, we took advantage of the longitudinal nature of the sample to examine if associations were stable across four educational time-points (from 7 to 12 years). Two SNPs in the KIAA0319 gene were nominally associated with rapid naming, and these associations were stable across different ages. Genetic association analysis with complex cognitive traits can be enriched through the use of longitudinal information on trait development.

51-0876 GF504 2012-33166 MARC Still the same hawk: reflections on nature and New York, ed. by John Waldman. Empire State Editions, 2013. 151p ISBN 9780823249893 pbk, $18.00 It is still [...]

51-0277 SD428 2012-30240 CIP Johnson, Christopher. Forests for the people: the story of America's eastern national forests, by Christopher Johnson and David Govatski. Island Press, 2013. 394p bibl index afp [...]

[e] 50-0264 [Internet Resource] DARBASE: Charles Darwin's Scientific Manuscripts URL: http://darwin.amnh.org/ [Visited Jun' 12] DARBASE is a freely available resource, hosted by the American Museum of Natural History since 2006. [...]

49-5052 QH81 2011-1294 CIP The Way of natural history, ed. by Thomas Lowe Fleischner. Trinity University, 2011. 218p afp ISBN 9781595340733, $45.00; ISBN 9781595340740 pbk, $16.95 The editor of this [...]

The article reports that Stefan Litwin came across Jean Paul through Schumann and his favorite author, to whom Schumann refers in several works as Schumann's polarity "Florestan" and "Eusebius" reflects not least that between the unworldly Walt and the pragmatic Vult.

49-0855 QL696 2010-25807 CIP Johnsgard, Paul A. Sandhill and whooping cranes: ancient voices over America's wetlands. Nebraska, 2011. 155p bibl index afp ISBN 9780803234963 pbk, $12.95ii Libraries and individuals who [...]

48-6285 QL737 2010-17206 CIP Mulvaney, Kieran. The great white bear: a natural and unnatural history of the polar bear. Houghton Mifflin Harcourt, 2011. 251p bibl index ISBN 9780547152424, $26.00 The [...]

Why is My Family My Family? Why is my brother my brother? Is he here to bug me, to annoy, to destroy me? is he here to be a spy, [...]

48-3854 QHI04 2010-19919 CIP Holland, Mary. Naturally curious: a photographic field guide and month-by-month journey through the fields, woods, and marshes of New England. Trafalgar Square, 2010. 473p bibl index [...]