Not So Rare: Errors of Metabolism during the Neonatal Period

During the neonatal period, the diagnosis of an error of metabolism (EM) was once thought to portend a poor prognosis or lethality. Over the past two decades, the prognosis of many EMs has changed. The critical aspect of the metabolic evaluation in a sick newborn is to rapidly identify whether there may be a metabolic problem. If there is a metabolic problem, the goal is to minimize the sequelae of the specific disorder. This review will explore how to approach and evaluate a newborn suspected of having an EM. A discussion of clinical and laboratory findings that often accompany EM will be included

Distrust And Dominance In Managing Alternative Work Arrangements: A Micro-Analytic Test Of Transaction Cost Theory

Organizations that successfully outsource may see better value-creation in creating a sustainable competitive advantage.  The objectives of this study were threefold:  a) provide a framework for studying the effects of perceived distrust that leads to dominance, b) analyze how opportunism parlays into the concept of dominance, and c) determine if the relationship between outsource partners varies by analyzing transaction characteristics.  Our research shows that firms should take caution to fully understand the effects that contract size has on a firm’s resources.&nbsp

Deploying the WTO Agreement on Government Procurement (GPA) to Enhance Sustainability and Accelerate Climate Change Mitigation

Mitigating climate change and promoting sustainability are defining challenges of our time. Public procurement has a vital role to play in responding to the current crises. This article makes the case that the World Trade Organization’s (WTO) Agreement on Government Procurement (GPA), and specifically the Work Programme on Sustainable Procurement that has been initiated pursuant to the Agreement, can serve as important instruments to promote sustainable approaches to public procurement internationally, consistent with the goals of climate change mitigation. The Work Programme, which was established at the time of the GPA’s modernization in 2012 and on which important work has already been done but which has recently been relatively dormant, mandates the Organization’s Committee on Government Procurement to study, inter alia, “the ways in which sustainable procurement can be practiced in a manner consistent with Parties’ international trade obligations ”and to prepare a report that sets out best practices concerning relevant measures and polices. This provides an essential and attractive platform for responding to the crisis. The article sets out important related background, including with respect to: (i) a “change of mindset” with respect to environmental sustainability which is already embodied in the amended GPA text adopted in 2012; (ii) existing GPA provisions that provide windows of opportunity for the advancing of related objectives; and (iii) importantly, ongoing developments in key GPA Parties and at the international level that both: (a) point the way toward meaningful change; and (b) suggest, in our view, a need for a modest degree of international coordination to avoid conflict and ensure continuing market openness. These developments portend a rich agenda of possibilities for further discussions in the WTO Work Programme

CHEMICALLY MODIFIED PHOTOSYNTHETIC BACTERIAL REACTION CENTERS: CIRCULAR DICHROISM, RAMAN RESONANCE, LOW TEMPERATURE ABSORPTION, FLUORESCENCE AND ODMR SPECTRA AND POLYPEPTIDE COMPOSITION OF BOROHYDRIDE TREATED REACTION CENTERS FROM Rhodobacter sphaeroides R26

Reaction centers from Rhodobacter sphaeroides have been modified by treatment with sodium borohydride similar to the original procedure [Ditson et al., Biochim. Biophys. Acta 766, 623 (1984)], and investigated spectroscopically and by gel electrophoresis. (1) Low temperature (1.2 K) absorption, fluorescence, absorption- and fluorescence-detected ODMR, and microwave-induced singlet-triplet absorption difference spectra (MIA) suggest that the treatment produces a spectroscopically homogeneous preparation with one of the ‘additional’ bacteriochlorophylls being removed. The modification does not alter the zero field splitting parameters of the primary donor triplet (TP870). (2) From the circular dichroism and Raman resonance spectra in the1500–1800 cm-1 region, the removed pigment is assigned to BchlM, e.g. the "extra" Bchl on the "inactive" M-branch. (3) A strong coupling among all pigment molecules is deduced from the circular dichroism spectra, because pronounced band-shifts and/or intensity changes occur in the spectral components assigned to all pigments. This is supported by distinct differences among the MIA spectra of untreated and modified reaction centers, as well as by Raman resonance. (4) The modification is accompanied by partial proteolytic cleavage of the M-subunit. The preparation is thus spectroscopically homogeneous, but biochemically heterogenous

Preserving entanglement under decoherence and sandwiching all separable states

Every entangled state can be perturbed, for instance by decoherence, and stay entangled. For a large class of pure entangled states, we show how large the perturbation can be. Our class includes all pure bipartite and all maximally entangled states. For an entangled state, E, the constucted neighborhood of entangled states is the region outside two parallel hyperplanes, which sandwich the set of all separable states. The states for which these neighborhoods are largest are the maximally entangled ones. As the number of particles, or the dimensions of the Hilbert spaces for two of the particles increases, the distance between two of the hyperplanes which sandwich the separable states goes to zero. It is easy to decide if a state Q is in the neighborhood of entangled states we construct for an entangled state E. One merely has to check if the trace of EQ is greater than a constant which depends upon E and which we determine.Comment: Corrected first author's e-mail address. All the rest remains unchange

Commitment to Breastfeeding in the Context of Phenylketonuria

Objective: To describe the meaning and importance of breastfeeding to mothers of infants with phenylketonuria (PKU). Design: Qualitative description. Setting: Mothers from the United States and Canada were recruited from the PKU Listserv and interviewed by telephone. Participants: Ten breastfeeding mothers with infants who had PKU and were younger than age 36 months. Methods: Mothers’ thoughts, decisions, and experiences of breastfeeding their infants with PKU were collected through telephone interviews. Interviews were transcribed verbatim, and data were analyzed using thematic descriptive analysis in the context of PKU. Results: Participants felt that that breastfeeding an infant with PKU was the healthiest choice and was therefore worth the labor. These women believed that this was what a loving mother would choose. As they continued to breastfeed their infants after diagnosis, the views of the participants changed. Initially they saw PKU as a disorder and felt that their infants were ill; later they felt that their infants were healthy in spite of PKU. Normal could mean a breastfeeding infant with PKU. Conclusion: Findings demonstrate the importance mothers attribute to breastfeeding and their willingness to invest considerable effort to breastfeed. Health care providers working with these mothers should help them strategize for success

Evaluation of miglustat as maintenance therapy after enzyme therapy in adults with stable type 1 Gaucher disease: a prospective, open-label non-inferiority study.

BACKGROUND: Previous studies have provided equivocal data on the use of miglustat as maintenance therapy in Gaucher disease type 1. We report findings from a clinical trial evaluating the effects of miglustat treatment in patients with stable type 1 Gaucher disease after enzyme therapy. METHODS: Adult type 1 Gaucher disease patients stabilized during at least 3 years of previous enzyme therapy were included in this 2-year, prospective, open-label non-inferiority study. The primary endpoint was percent change from baseline in liver volume. Secondary endpoints included changes in spleen volume, hemoglobin concentration and platelet count. RESULTS: Forty-two patients were enrolled (mean±SD age, 45.1±12.7 years; previous enzyme therapy duration 9.5±4.0 years). Median (range) exposure to miglustat 100 mg t.i.d. was 658 (3-765) days. Twenty-one patients discontinued treatment prematurely; 13 due to adverse events, principally gastrointestinal. The upper 95% confidence limit of mean percent change in liver volume from baseline to end of treatment was below the non-inferiority margin of 10% (-1.1%; 95%CI -6.0, 3.9%). Mean (95%CI) changes in spleen volume, hemoglobin concentration and platelet count were 102 (24,180) mL, -0.95 (-1.38, -0.53) g/dL and -44.1 (-57.6, -30.7) ×109/L, respectively. CONCLUSIONS: The primary efficacy endpoint was met; overall there was no change in liver volume during 24 months of miglustat therapy. Several patients showed a gradual deterioration in some disease manifestations, suggesting that miglustat could maintain clinical stability, but not in all patients. Miglustat demonstrated a predictable profile of safety and tolerability that was consistent with that reported in previous clinical trials and experience in clinical practice. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00319046.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

(+)-(1S,5R,10S)-11,11-Dimeth­yl-4-oxa­tricyclo­[8.4.0.01,5]tetra­deca­ne-3,12-dione

The title compound, C15H22O3, was prepared via amino-acid-promoted Robinson annulation followed by tandem Pd/C-mediated hydrogenation and oxidative cyclization. This product was instrumental in determining the feasibility of a stereocontrolled hydrogenation in which the directing hydroxyl group is adjacent to the 6–7-ring network and its olefinic component. The asymmetric unit consists of a single mol­ecule with normal geometric parameters. The absolute configuration was assigned based on the known enanti­omeric prescursor. Inter­molecular C—H⋯O inter­actions link each mol­ecule with four neighboring mol­ecules

Profiling Sterols in Cerebrotendinous Xanthomatosis: Utility of Girard Derivatization and High Resolution Exact Mass LC-ESI-MSn Analysis

In this study we profile free 3-oxo sterols present in plasma from patients affected with the neurodegenerative disorder of sterol and bile acid metabolism cerebrotendinous xanthomatosis (CTX), utilizing a combination of charge-tagging and LC-ESI-MSn performed with an LTQ-Orbitrap Discovery instrument. In addition, we profile sterols in plasma from 24-month-old cyp27A1 gene knockout mice lacking the enzyme defective in CTX. Charge-tagging was accomplished by reaction with cationic Girard\u27s P (GP) reagent 1-(carboxymethyl) pyridinium chloride hydrazide, an approach uniquely suited to studying the 3-oxo sterols that accumulate in CTX, as Girard\u27s reagent reacts with the sterol oxo moiety to form charged hydrazone derivatives. The ability to selectively generate GP-tagged 3-oxo-4-ene and 3-oxo-5(H) saturated plasma sterols enabled ESI-MSn analysis of these sterols in the presence of a large excess (3 orders of magnitude) of cholesterol. Often cholesterol detected in biological samples makes it challenging to quantify minor sterols, with cholesterol frequently removed prior to analysis. We derivatized plasma (10μl) without SPE removal of cholesterol to ensure detection of all sterols present in plasma. We were able to measure 4-cholesten-3-one in plasma from untreated CTX patients (1207±302ng/ml, mean±SD, n=4), as well as other intermediates in a proposed pathway to 5α-cholestanol. In addition, a number of bile acid precursors were identified in plasma using this technique. GP-tagged sterols were identified utilizing high resolution exact mass spectra (±5ppm), as well as MS2 ([M]+→) spectra that possessed characteristic neutral loss of 79Da (pyridine) fragment ions, and MS3 ([M]+→[M-79]+→) spectra that provided additional structurally informative fragment ions. © 2010 Elsevier B.V