On the Complexity of Recognizing Iterated Differences of Polyhedra

The iterated difference of polyhedra $V = P_1 \backslash ( P_2 \backslash (... P_k ) ... )$ has been proposed independently in [Zwie-Aart-Wess92] and [Shon93] as a sufficient condition for $V$ to be exactly computable by a two-layered neural network. An algorithm checking whether $V$ included in $R^d$ is an iterated difference of polyhedra is proposed in [Zwie-Aart-Wess92]. However, this algorithm is not practically usable because it has a high computational complexity and it was only conjectured to stop with a negative answer when applied to a region which is not an iterated difference of polyhedra. This paper sheds some light on the nature of iterated difference of polyhedra. The outcomes are\,: (i) an algorithm which always stops after a small number of iterations, (ii) sufficient conditions for this algorithm to be polynomial and (iii) the proof that an iterated difference of polyhedra can be exactly computed by a two-layered neural network using only essential hyperplanes

Medication in older patients reviewed multiple ways (MORE) study

Background Polypharmacy in older patients can lead to potentially inappropriate prescribing. The risk of the latter calls for effective medication review to ensure proper medication usage and safety. Objective Provide insight on the similarities and differences of medication review done in multiple ways that may lead to future possibilities to optimize medication review. Setting This study was conducted in Zuyderland Medical Centre, the second largest teaching hospital in the Netherlands. Method This descriptive study compares the quantity and content of remarks identified by medication review performed by a geriatrician, outpatient pharmacist, and Clinical Decision Support System. The content of remarks is categorized in seven categories of possible pharmacotherapeutic problems: ‘indication without medication’, ‘medication without indication’, ‘contra-indication/interaction/side-effect’, ‘dosage problem’, ‘double medication’, ‘incorrect medication’ and ‘therapeutic drug monitoring’. Main outcome measure Number and content of remarks on medication review. Results The Clinical Decision Support System (1.8 ± 0.8 vs. 0.9 ± 0.9, p < 0.001) and outpatient pharmacist (1.8 ± 0.8 vs. 0.9 ± 0.9, p = 0.045) both noted remarks in significantly more categories than the geriatricians. The Clinical Decision Support System provided more remarks on ‘double medication’, ‘dosage problem’ and ‘contraindication/interaction/side effects’ than the geriatrician (p < 0.050), while the geriatrician did on ‘medication without indication’ (p < 0.001). The Clinical Decision Support System noted significantly more remarks on ‘contraindication/interaction/side effects’ and ‘therapeutic drug monitoring’ than the outpatient pharmacist, whereas the outpatient pharmacist reported more on ‘indication without medication’ and ‘medication without indication’ than the Clinical Decision Support System (p ≤ 0.007). Conclusion Medication review performed by a geriatrician, outpatient pharmacist, and Clinical Decision Support System provides different insights and should be combined to create a more comprehensive report on medication profiles

A single point mutation in the Listeria monocytogenes ribosomal gene rpsU enables SigB activation independently of the stressosome and the anti-sigma factor antagonist RsbV

Microbial population heterogeneity leads to different stress responses and growth behavior of individual cells in a population. Previously, a point mutation in the rpsU gene (rpsUG50C) encoding ribosomal protein S21 was identified in a Listeria monocytogenes LO28 variant, which leads to increased multi-stress resistance and a reduced maximum specific growth rate. However, the underlying mechanisms of these phenotypic changes remain unknown. In L. monocytogenes, the alternative sigma factor SigB regulates the general stress response, with its activation controlled by a series of Rsb proteins, including RsbR1 and anti-sigma factor RsbW and its antagonist RsbV. We combined a phenotype and proteomics approach to investigate the acid and heat stress resistance, growth rate, and SigB activation of L. monocytogenes EGDe wild type and the ΔsigB, ΔrsbV, and ΔrsbR1 mutant strains. While the introduction of rpsUG50C in the ΔsigB mutant did not induce a SigB-mediated increase in robustness, the presence of rpsUG50C in the ΔrsbV and the ΔrsbR1 mutants led to SigB activation and concomitant increased robustness, indicating an alternative signaling pathway for the SigB activation in rpsUG50C mutants. Interestingly, all these rpsUG50C mutants exhibited reduced maximum specific growth rates, independent of SigB activation, possibly attributed to compromised ribosomal functioning. In summary, the increased stress resistance in the L. monocytogenes EGDe rpsUG50C mutant results from SigB activation through an unknown mechanism distinct from the classical stressosome and RsbV/RsbW partner switching model. Moreover, the reduced maximum specific growth rate of the EGDe rpsUG50C mutant is likely unrelated to SigB activation and potentially linked to impaired ribosomal function

Workplace learning from a socio-cultural perspective: creating developmental space during the general practice clerkship

Workplace learning in undergraduate medical education has predominantly been studied from a cognitive perspective, despite its complex contextual characteristics, which influence medical students’ learning experiences in such a way that explanation in terms of knowledge, skills, attitudes and single determinants of instructiveness is unlikely to suffice. There is also a paucity of research which, from a perspective other than the cognitive or descriptive one, investigates student learning in general practice settings, which are often characterised as powerful learning environments. In this study we took a socio-cultural perspective to clarify how students learn during a general practice clerkship and to construct a conceptual framework that captures this type of learning. Our analysis of group interviews with 44 fifth-year undergraduate medical students about their learning experiences in general practice showed that students needed developmental space to be able to learn and develop their professional identity. This space results from the intertwinement of workplace context, personal and professional interactions and emotions such as feeling respected and self-confident. These forces framed students’ participation in patient consultations, conversations with supervisors about consultations and students’ observation of supervisors, thereby determining the opportunities afforded to students to mind their learning. These findings resonate with other conceptual frameworks and learning theories. In order to refine our interpretation, we recommend that further research from a socio-cultural perspective should also explore other aspects of workplace learning in medical education

Evaluation of antimicrobial effectiveness of pimaricin-loaded thermosensitive nanohydrogels in grape juice

Pimaricin-loaded poly(N-isopropylacrylamide) nanohydrogels with and without acrylic acid, were evaluated as food-spoilage inhibitors in a model system and a real food product: grape juice. Pimaricin was proposed as a non-allergenic alternative to sulphites for protecting juices against recontamination. However, pimaricin may degrade under conditions and treatments (heating, acidification, lighting) commonly applied in producing fresh juices. Nanohydrogel encapsulation may be a feasible procedure to avoid pimaricin degradation, improving its antimicrobial activity. Pimaricin-free nanohydrogels did not affect the growth of the indicator yeast either in the food model system or in grape juice. Conversely, pimaricin-loaded nanohydrogels effectively inhibited the growth of the indicator yeast. In some cases, the inhibition was extended even further than using free pimaricin. For instance, in the food model system, pimaricin-loaded nanohydrogels with acrylic acid (NPPNIPA-20AA(5)) prevented the yeast growth for more than 81 h while free pimaricin was only effective for 12 h. Despite pimaricin-loaded nanohydrogels without acrylic acid (NPPNIPA(5)) were able to reduce maximum yeast growth, as in all treatments with pimaricin, the extent of the inhibitory effect was not significantly (p>0.05) different to that achieved with free pimaricin. In grape juice, both free pimaricin and NPPNIPA-20AA(5) treatment completely inhibited the growth of the indicator yeast until the end of the bioassay. However, the latter provided similar inhibition levels using a smaller amount of pimaricin due to PNIPA-20AA(5) protection and its controlled release from the nanohydrogel. Therefore, nanohydrogel encapsulation may help to optimise antifungal treatments and decrease the incidence of food allergies.Funded by grant (MAT 2006-11662-CO3-CO2-C01/MAT 2010-21509-C03-01/EUI 2008-00115) from the “Ministerio de Educación y Ciencia” (Spain). Grant (SFRH/BPD/87910/2012) from the Fundação para a Ciência e Tecnologia (FCT, Portugal). Marie Curie COFUND Postdoctoral Research Fellow

Production of medium-chain fatty acids and higher alcohols by a synthetic co-culture grown on carbon monoxide or syngas

Synthesis gas, a mixture of CO, H2, and CO2, is a promising renewable feedstock for bio-based production of organic chemicals. Production of medium-chain fatty acids can be performed via chain elongation, utilizing acetate and ethanol as main substrates. Acetate and ethanol are main products of syngas fermentation by acetogens. Therefore, syngas can be indirectly used as a substrate for the chain elongation process.ERC Grant (Project 323009) and the Gravitation Grant (Project 024.002.002) of the Netherlands Ministry of Education, Culture and Science, and the Netherlands Science Foundation (NWO

Bistability and Bacterial Infections

Bacterial infections occur when the natural host defenses are overwhelmed by invading bacteria. The main component of the host defense is impaired when neutrophil count or function is too low, putting the host at great risk of developing an acute infection. In people with intact immune systems, neutrophil count increases during bacterial infection. However, there are two important clinical cases in which they remain constant: a) in patients with neutropenic-associated conditions, such as those undergoing chemotherapy at the nadir (the minimum clinically observable neutrophil level); b) in ex vivo examination of the patient's neutrophil bactericidal activity. Here we study bacterial population dynamics under fixed neutrophil levels by mathematical modelling. We show that under reasonable biological assumptions, there are only two possible scenarios: 1) Bacterial behavior is monostable: it always converges to a stable equilibrium of bacterial concentration which only depends, in a gradual manner, on the neutrophil level (and not on the initial bacterial level). We call such a behavior type I dynamics. 2) The bacterial dynamics is bistable for some range of neutrophil levels. We call such a behavior type II dynamics. In the bistable case (type II), one equilibrium corresponds to a healthy state whereas the other corresponds to a fulminant bacterial infection. We demonstrate that published data of in vitro Staphylococcus epidermidis bactericidal experiments are inconsistent with both the type I dynamics and the commonly used linear model and are consistent with type II dynamics. We argue that type II dynamics is a plausible mechanism for the development of a fulminant infection