Smoke and 'Miros', Design and Magic

Magic is the essence of creativity; of action that operates outside the boundaries of plans, programs and exact- techniques. Following the launch of ‘Design and Magic’ (DTG, London), four of the contributing authors expand the idea that designers are failed magicians and magicians are failed designers. Magic in all its various guises is seen to present an infinite realm of possibilities for design, not least its link with a readymade meta- reality. The power of transformation that drives the creative practitioner is not dissimilar to the power of the alchemist in creating precious substances. Their rituals and tools might be different, but the effect is the same. Faced with the apparent contradictions of functionalist technology and magical product narratives, the paper seeks to demonstrate that design can re-engage with the emotional and poetic. It asks whether practitioners should pursue the notion of design as deception, fuelling a gluttony of material desire, or should they look to a higher order, where magic provides a holistic view, at least 180 degrees of which is not accounted for right now

14N and 15N coupling constants of the oxidized primary donor P-860 of bacterial photosynthesis obtained by electron spin echo envelope modulation spectroscopy

An electron spin echo modulation frequency analysis of P+-860 is performed in 14N chromatophores of Rhodospirillum rubrum, and in 15N substituted reaction centers from Rhodopseudomonas sphaeroides 2.4.1. For the 14N material two sets of nuclear quadrupole parameters are obtained. From the frequencies found for 15N reaction centers the perpendicular, parallel and isotropic hyperfine previous termcouplingnext term constants of three of the four bacteriochlorophyll nitrogen nuclei are inferred

Quantitative phosphoproteomics to unravel the cellular response to chemical stressors with different modes of action

Damage to cellular macromolecules and organelles by chemical exposure evokes activation of various stress response pathways. To what extent different chemical stressors activate common and stressor-specific pathways is largely unknown. Here, we used quantitative phosphoproteomics to compare the signaling events induced by four stressors with different modes of action: the DNA damaging agent: cisplatin (CDDP), the topoisomerase II inhibitor: etoposide (ETO), the pro-oxidant: diethyl maleate (DEM) and the immunosuppressant: cyclosporine A (CsA) administered at an equitoxic dose to mouse embryonic stem cells. We observed major differences between the stressors in the number and identity of responsive phosphosites and the amplitude of phosphorylation. Kinase motif and pathway analyses indicated that the DNA damage response (DDR) activation by CDDP occurs predominantly through the replication-stress-related Atr kinase, whereas ETO triggers the DDR through Atr as well as the DNA double-strand-break-associated Atm kinase. CsA shares with ETO activation of CK2 kinase. Congruent with their known modes of action, CsA-mediated signaling is related to down-regulation of pathways that control hematopoietic differentiation and immunity, whereas oxidative stress is the most prominent initiator of DEM-modulated stress signaling. This study shows that even at equitoxic doses, different stressors induce distinctive and complex phosphorylation signaling cascades.Toxicolog

Structural identification and biological activity of 7-methyl-10,11-ethylenedioxy-20(S)-camptothecin, a photodegradant of lurtotecan

An additional chromatographic peak was observed in plasma samples of patients receiving NX 211, a liposomal formulation of the topoisomerase I inhibitor lurtotecan. We have isolated and purified this product by sequential solid-phase extractions, and we report its structure and cytotoxicity relative to lurtotecan and related agents. Nuclear magnetic resonance data indicate that cleavage of the piperazino moiety occurred at the N-C bond of the B-ring, yielding 7-methyl-10,11-ethylenedioxy-20(S)-camptothecin (MEC). Tests of the growth inhibition potential of MEC in seven human tumor cell lines showed that the compound was approximately 2-18-fold more cytotoxic than lurtotecan, topotecan, and 7-ethyl-10-hydroxy-20(S)-camptothecin (SN-38). Subsequently, we found that MEC was the product of rapid photolysis of lurtotecan, with the rate of degradation inversely proportional to NX 211 concentrations, and greatly depends on light intensity. Furthermore, MEC concentrations were found to increase significantly in plasma samples exposed to laboratory light but not in blood. MEC was not produced from NX 211 in the presence of human liver microsomes, suggesting that it is not a product of cytochrome P-450 metabolism. Using a validated analytical method, trace levels of MEC were quantitated in blood samples of two patients. These observations confirm that the precautions for protection from light currently specified for preparation and administration of NX 211 dose solutions are critical. Procedures to minimize formation of MEC, by the use of amber vials for NX 211 and by preparation of dilutions immediately before clinical use in a fashion completely protected from light, are now being routinely implemented

Persistence of clones of coagulase-negative staphylococci among premature neonates in neonatal intensive care units: two-center study of bacterial genotyping and patient risk factors

From 1 January 1995 until 1 January 1996, we studied the molecular epidemiology of blood isolates of coagulase-negative staphylococci (CoNS) in the Neonatal Intensive Care Units (NICUs) of the Sophia Children's Hospital (SCH; Rotterdam, The Netherlands) and the Wilhelmina Children's Hospital (WCH; Utrecht, The Netherlands). The main goal of the present study was to detect putatively endemic clones of CoNS persisting in these NICUs. Pulsed-field gel electrophoresis was used to detect the possible presence of endemic clones of clinical significance. In addition, clinical data of patients in the SCH were analyzed retrospectively to identify risk factors for the acquisition of positive blood cultures. In both centers, endemic CoNS clones were persistently present. Thirty-three percent of the bacterial isolates derived from blood cultures in the SCH belonged to a single genotype. In the WCH, 45% of all bacterial strains belonged to a single clone. These clones were clearly different from each other, which implies that site specificity is involved. Interestingly, we observe that the clonal type in the SCH differed significantly from the incidentally occurring strains with respect to both the average pH and partial CO2 pressure of the patient's blood at the time of bacterial culture. We found that the use of intravascular catheters, low gestational age, and a long hospital stay were important risk factors for the development of a putative CoNS infection. When the antibiotic susceptibility of the bacterial isolates was assessed, a clear correlation between the nature of the antibiotics most frequently used as a first line of defense versus the resistance profile was observed. We conclude that the intensive use of antibiotics in an NICU setting with highly susceptible patients causes selection of multiresistant clones of CoNS which subsequently become endemic

Targeted social care for highly vulnerable pregnant women: Protocol of the Mothers of Rotterdam cohort study

Introduction: Social vulnerability is known to be related to ill health. When a pregnant woman is socially vulnerable, the ill health does not only affect herself, but also the health and development of her (unborn) child. To optimise care for highly vulnerable pregnant women, in Rotterdam, a holistic programme was developed in close collaboration between the university hospital, the local government and a non-profit organisation. This programme aims to organise social and medical care from pregnancy until the second birthday of the child, while targeting adult and child issues simultaneously. In 2014, a pilot in the municipality of Rotterdam demonstrated the significance of this holistic approach for highly vulnerable pregnant women. In the Mothers of Rotterdam' study, we aim to prospectively evaluate the effectiveness of the holistic approach, referred to as targeted social care. Methods and analysis: The Mothers of Rotterdam study is a pragmatic prospective cohort study planning to include 1200 highly vulnerable pregnant women for the comparison between targeted social care and care as usual. Effectiveness will be compared on the following outcomes: (1) child development (does the child show adaptive development at year 1?) and (2) maternal mental health (is maternal distress reduced at the end of the social care programme?). Propensity scores will be used to correct for baseline differences between both social care programmes. Ethics and dissemination: The prospective cohort study was approved by the Erasmus Medical Centre Ethics Committee (ref. no. MEC-2016-012) and the first results of the study are expected to be available in the second half of 2019 through publication in peer-reviewed international journals. Trial registration number NTR6271; Pre-results

Intragraft interleukin 2 mRNA expression during acute cellular rejection and left ventricular total wall thickness after heart transplantation

OBJECTIVE: To assess whether diastolic graft function is influenced by intragraft interleukin 2 (IL-2) messenger RNA (mRNA) expression in rejecting cardiac allografts. DESIGN: 16 recipients of cardiac allografts were monitored during the first three months after transplantation. The presence of IL-2 mRNA in endomyocardial biopsies (n = 123) was measured by reverse transcriptase polymerase chain reaction. To determine heart function, concurrent M mode and two dimensional Doppler echocardiograms were analysed. RESULTS: Histological signs of acute rejection (International Society for Heart and Lung Transplantation (ISHLT) rejection grade > 2) were strongly associated with IL-2 mRNA expression (IL-2 mRNA was present in 12 of 20 endomyocardial biopsies (60%) with acute rejection and in 24 of 103 endomyocardial biopsies (23%) without acute rejection, p = 0.002). No significant relation was found between either histology or IL-2 mRNA expression alone and the studied echocardiographic parameters. However, stratification of the echocardiographic data into those of patients with and those without acute rejection showed that during acute rejection IL-2 mR

5 years of experience implementing a methicillin-resistant Staphylococcus aureus search and destroy policy at the largest university medical center in the Netherlands

OBJECTIVE: To evaluate the effectiveness of a rigorous search and destroy policy for controlling methicillin-resistant Staphylococcus aureus (MRSA) infection or colonization. DESIGN: Hospital-based observational follow-up study. SETTING: Erasmus University Medical Center Rotterdam, a 1,200-bed tertiary care center in Rotterdam, the Netherlands. METHODS: Outbreak control was accomplished by the use of active surveillance cultures for persons at risk, by the preemptive isolation of patients at risk, and by the strict isolation of known MRSA carriers and the eradication of MRSA carriage. For unexpected cases of MRSA colonization or infection, patients placed in strict isolation or contact isolation and healthcare workers (HCWs) were screened. We collected data from 2000-2004. RESULTS: During the 5-year study period, 51,907 MRSA screening culture

Prevalence of sensitization to the predatory mite Amblyseius cucumeris as a new occupational allergen in horticulture

Background: Protection against thrips, a common pest in bell pepper horticulture is effectively possible without pesticides by using the commercially available predatory mite Amblyseius cucumeris (Ac). The prevalence of sensitization to Ac among exposed greenhouse employees and its clinical relevance was studied. Methods: Four hundred and seventytwo employees were asked to fill in a questionnaire and were tested on location. Next to RAST, skin prick tests (SPTs) were performed with common inhalant allergens, the storage mite Tyrophagus putrescentiae (Tp) which serves as a temporary food source during the cultivation process and Ac. Furthermore, nasal challenge tests with Ac were carried out in 23 sensitized employees. Results: SPTs positive to Ac were found in 109 employees (23%). Work-related symptoms were reported by 76.1%. Sensitization to Tp was found in 62 employees of whom 48 were also sensitized to Ac. Immunoglobulin (Ig)E-mediated allergy to inhalant allergens appeared to be an important risk factor for sensitization to Ac. Employees with rhinitis symptoms showed a significantly higher response to all Ac doses during the nasal challenge test compared with employees without rhinitis symptoms. Conclusions: The predatory mite Ac is a new occupational allergen in horticulture which can cause an IgE-mediated allergy in exposed employees. It is biologically active on the mucous membranes of the nose and therefore clinically relevant for the development of work-related symptoms

Modulation of CD8\u3csup\u3e+\u3c/sup\u3e T cell responses to AAV vectors with IgG-derived MHC class II epitopes

Immune responses directed against viral capsid proteins constitute a main safety concern in the use of adeno-associated virus (AAV) as gene transfer vectors in humans. Pharmacological immunosuppression has been proposed as a solution to the problem; however, the approach suffers from several potential limitations. Using MHC class II epitopes initially identified within human IgG, named Tregitopes, we showed that it is possible to modulate CD8+ T cell responses to several viral antigens in vitro. We showed that incubation of peripheral blood mononuclear cells with these epitopes triggers proliferation of CD4+CD25+FoxP3+ T cells that suppress killing of target cells loaded with MHC class I antigens in an antigen- specific fashion, through a mechanism that seems to require cell-to-cell contact. Expression of a construct encoding for the AAV capsid structural protein fused to Tregitopes resulted in reduction of CD8+ T cell reactivity against the AAV capsid following immunization with an adenoviral vector expressing capsid. This was accompanied by an increase in frequency of CD4+CD25+FoxP3+ T cells in spleens and lower levels of inflammatory infiltrates in injected tissues. This proof-of-concept study demonstrates modulation of CD8+ T cell reactivity to an antigen using regulatory T cell epitopes is possible