Nasal decolonization of Staphylococcus aureus with mupirocin: strengths, weaknesses and future prospects

Staphylococcus aureus in the nose is a risk factor for endogenous staphylococcal infection. UK guidelines recommend the use of mupirocin for nasal decolonization in certain groups of patients colonized with methicillin-resistant S. aureus (MRSA). Mupirocin is effective at removing S. aureus from the nose over a few weeks, but relapses are common within several months. There are only a few prospective randomized clinical trials that have been completed with sufficient patients, but those that have been reported suggest that clearance of S. aureus from the nose is beneficial in some patient groups for the reduction in the incidence of nosocomial infections. There is no convincing evidence that mupirocin treatment reduces the incidence of surgical site infection. New antibiotics are needed to decolonize the nose because bacterial resistance to mupirocin is rising, and so it will become less effective. Furthermore, a more bactericidal antibiotic than mupirocin is needed, on the grounds that it might reduce the relapse rate, and so clear the patient of MRSA for a longer period of time than mupirocin

Evaluation of uncertainty in alignment tensors obtained from dipolar couplings

Residual dipolar couplings and their corresponding alignment tensors are useful for structural analysis of macromolecules. The error in an alignment tensor, derived from residual dipolar couplings on the basis of a known structure, is determined not only by the accuracy of the measured couplings but also by the uncertainty in the structure (structural noise). This dependence is evaluated quantitatively on the basis of simulated structures using Monte-Carlo type analyses. When large numbers of dipolar couplings are available, structural noise is found to result in a systematic underestimate of the magnitude of the alignment tensor. Particularly in cases where only few dipolar couplings are available, structural noise can cause significant errors in best-fitted alignment tensor values, making determination of the relative orientation of small fragments and evaluation of local backbone mobility from dipolar couplings difficult. An example for the protein ubiquitin demonstrates the inherent limitations in characterizing motions on the basis of local alignment tensor magnitudes

Poor Outcome in a Mitochondrial Neurogastrointestinal Encephalomyopathy Patient with a Novel TYMP Mutation: The Need for Early Diagnosis.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a devastating autosomal recessive disorder due to mutations in TYMP, which cause loss of function of thymidine phosphorylase (TP), nucleoside accumulation in plasma and tissues and mitochondrial dysfunction. The clinical picture includes progressive gastrointestinal dysmotility, cachexia, ptosis and ophthalmoparesis, peripheral neuropathy and diffuse leukoencephalopathy, which usually lead to death in early adulthood. Therapeutic options are currently available in clinical practice (allogeneic hematopoietic stem cell transplantation and carrier erythrocyte entrapped TP therapy) and newer, promising therapies are expected in the near future. However, successful treatment is strictly related to early diagnosis. We report on an incomplete MNGIE phenotype in a young man harboring the novel heterozygote c.199 C>T (Q67X) mutation in exon 2, and the previously reported c.866 A>C (E289A) mutation in exon 7 in TYMP. The correct diagnosis was achieved many years after the onset of symptoms and unfortunately, the patient died soon after diagnosis because of multiorgan failure due to severe malnutrition and cachexia before any therapeutic option could be tried. To date, early diagnosis is essential to ensure that patients have the opportunity to be treated. MNGIE should be suspected in all patients who present with both gastrointestinal and nervous system involvement, even if the classical complete phenotype is lacking

The different dimensions of livelihood impacts of Payments for Environmentals Services (PES) schemes: A systematic review

Through a systematic review of peer-reviewed and grey literature, this paper analyzes evidence of the livelihood impacts of Payments for Environmental Services (PES). Forty-six studies assessed PES livelihood impacts. The assessments presented more positive livelihood impacts than negative ones, focusing on financial benefits. Non-monetary and non-material impacts of PES were largely understudied. Most reviews focused on ES providers, hindering the understanding of broader societal impacts. The review yielded examples where participants lost from their participation or where improvements in one livelihood dimension paralleled deterioration in another. Consequently, we identified key research gaps in: i) understanding the social and cultural impacts of PES, ii) evaluating environmental and economic additionality from improving other ES at the expense of cultural ones, iii) and assessing PES impacts in terms of trade-offs between multiple livelihood dimensions. Moreover, increased knowledge is needed on the impact of PES on changes in household expenditure and choice, and on trade-offs between household income and inequality in ES provider communities. Finally, if PES schemes are implemented to sustainably improve livelihoods, targeting disaggregated populations, understanding equity and social power relations within and between ES providers and users, and better monitoring and evaluation systems that consider locally relevant livelihood dimensions are needed

Quantification of Plasma and Urine Thymidine and 2'-Deoxyuridine by LC-MS/MS for the Pharmacodynamic Evaluation of Erythrocyte Encapsulated Thymidine Phosphorylase in Patients with Mitochondrial Neurogastrointestinal Encephalomyopathy.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare disorder caused by mutations in TYMP, leading to a deficiency in thymidine phosphorylase and a subsequent systemic accumulation of thymidine and 2'-deoxyuridine. Erythrocyte-encapsulated thymidine phosphorylase (EE-TP) is under clinical development as an enzyme replacement therapy for MNGIE. Bioanalytical methods were developed according to regulatory guidelines for the quantification of thymidine and 2'-deoxyuridine in plasma and urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for supporting the pharmacodynamic evaluation of EE-TP. Samples were deproteinized with 5% perchloric acid (v/v) and the supernatants analyzed using a Hypercarb column (30 × 2.1 mm, 3 µm), with mobile phases of 0.1% formic acid in methanol and 0.1% formic acid in deionized water. Detection was conducted using an ion-spray interface running in positive mode. Isotopically labelled thymidine and 2'-deoxyuridine were used as internal standards. Calibration curves for both metabolites showed linearity (r > 0.99) in the concentration ranges of 10-10,000 ng/mL for plasma, and 1-50 µg/mL for urine, with method analytical performances within the acceptable criteria for quality control samples. The plasma method was successfully applied to the diagnosis of two patients with MNGIE and the quantification of plasma metabolites in three patients treated with EE-TP

Families with infants: a general approach to solve hard partition problems

We introduce a general approach for solving partition problems where the goal is to represent a given set as a union (either disjoint or not) of subsets satisfying certain properties. Many NP-hard problems can be naturally stated as such partition problems. We show that if one can find a large enough system of so-called families with infants for a given problem, then this problem can be solved faster than by a straightforward algorithm. We use this approach to improve known bounds for several NP-hard problems as well as to simplify the proofs of several known results. For the chromatic number problem we present an algorithm with $O^*((2-\varepsilon(d))^n)$ time and exponential space for graphs of average degree $d$. This improves the algorithm by Bj\"{o}rklund et al. [Theory Comput. Syst. 2010] that works for graphs of bounded maximum (as opposed to average) degree and closes an open problem stated by Cygan and Pilipczuk [ICALP 2013]. For the traveling salesman problem we give an algorithm working in $O^*((2-\varepsilon(d))^n)$ time and polynomial space for graphs of average degree $d$. The previously known results of this kind is a polyspace algorithm by Bj\"{o}rklund et al. [ICALP 2008] for graphs of bounded maximum degree and an exponential space algorithm for bounded average degree by Cygan and Pilipczuk [ICALP 2013]. For counting perfect matching in graphs of average degree~$d$ we present an algorithm with running time $O^*((2-\varepsilon(d))^{n/2})$ and polynomial space. Recent algorithms of this kind due to Cygan, Pilipczuk [ICALP 2013] and Izumi, Wadayama [FOCS 2012] (for bipartite graphs only) use exponential space.Comment: 18 pages, a revised version of this paper is available at http://arxiv.org/abs/1410.220

The use of ICT in the assessment of modern languages: the English context and European viewpoints

The ever increasing explosion of highly attractive multimedia resources on offer has boosted the use of information and communication technology (ICT) in the teaching and learning of modern languages. The use of ICT to assess languages is less frequent, however, although online testing is starting to develop. This paper examines the national context for the assessment of modern foreign language proficiency in England, outlines the kinds of assessment currently available and the development of electronic forms of assessment and compares the above with the survey results of a European Union (EU) funded project on current good practice in online assessment of languages in other European countries. The findings indicate that speaking is inadequately served by online testing as tests currently focus primarily on receptive language skills. The implications for future successful online testing include the incorporation of interactive skills and effective formative feedback