Kinetic Control of Interpenetration in Fe-Biphenyl-4,4 '-dicarboxylate Metal-Organic Frameworks by Coordination and Oxidation Modulation

Phase control in the self-assembly of metal–organic frameworks (MOFs) is often a case of trial and error; judicious control over a number of synthetic variables is required to select the desired topology and control features such as interpenetration and defectivity. Herein, we present a comprehensive investigation of self-assembly in the Fe–biphenyl-4,4′-dicarboxylate system, demonstrating that coordination modulation can reliably tune between the kinetic product, noninterpenetrated MIL-88D(Fe), and the thermodynamic product, two-fold interpenetrated MIL-126(Fe). Density functional theory simulations reveal that correlated disorder of the terminal anions on the metal clusters results in hydrogen bonding between adjacent nets in the interpenetrated phase and this is the thermodynamic driving force for its formation. Coordination modulation slows self-assembly and therefore selects the thermodynamic product MIL-126(Fe), while offering fine control over defectivity, inducing mesoporosity, but electron microscopy shows MIL-88D(Fe) persists in many samples despite not being evident by diffraction. Interpenetration control is also demonstrated using the 2,2′-bipyridine-5,5′-dicarboxylate linker; it is energetically prohibitive for it to adopt the twisted conformation required to form the interpenetrated phase, although multiple alternative phases are identified due to additional coordination of Fe cations to its N donors. Finally, we introduce oxidation modulation—the use of metal precursors in different oxidation states from that found in the final MOF—to kinetically control self-assembly. Combining coordination and oxidation modulation allows the synthesis of pristine MIL-126(Fe) with BET surface areas close to the predicted maximum for the first time, suggesting that combining the two may be a powerful methodology for the controlled self-assembly of high-valent MOFs

Follow-up after paediatric intensive care treatment: parental postraumatic stress

Aim: To study the prevalence of posttraumatic stress in parents after an acute admission to a paediatric intensive care unit (PICU) and to determine risk factors for the development of posttraumatic stress. Methods: Parents completed posttraumatic stress questionnaires three months after their child's discharge. This questionnaire measures both symptoms of posttraumatic stress disorder (PTSD) and enables determination of the full psychiatric diagnosis of PTSD. Medical and demographic data concerning their child were gathered from physical evaluations three months after discharge. Of 250 eligible families, 144 (57.6%) participated in this study. The questionnaires were completed by 140 mothers and 107 fathers. Results: More than three-quarters of the parents experienced persistent symptoms of PTSD. In 21 mothers (15.0%) and 10 fathers (9.3%), the full psychiatric diagnosis of PTSD was determined. In six families, both parents had PTSD. Furthermore, a significant positive correlation was found between symptoms of PTSD of the mothers and the fathers. No obvious medical risk factors could be distinguished. Conclusion: The unexpected admission of a child to a PICU is a stressful event associated with parental posttraumatic stress. Treatment should not end after discharge. Follow-up care is warranted and research should be focused on prevention of these symptoms. © 2007 The Author(s)

Spatial Learning and Wayfinding in an Immersive Environment: The Digital Fulldome

Previous work has examined whether immersive technologies can benefit learning in virtual environments, but the potential benefits of technology in this context are confounded by individual differences such as spatial ability. We assessed spatial knowledge acquisition in male and female participants using a technology not previously examined empirically: the digital fulldome. Our primary aim was to examine whether performance on a test of survey knowledge was better in a fulldome (N = 28, 12 males) relative to a large, flat screen display (N = 27, 13 males). Regression analysis showed that, compared to a flat screen display, males showed higher levels of performance on a test of survey knowledge after learning in the fulldome, but no benefit occurred for females. Furthermore, performance correlated with spatial visualization ability in male participants, but not in female participants. Thus, the digital fulldome is a potentially useful learning aid, capable of accommodating multiple users, but individual differences and use of strategy need to be considered

Competition of Escherichia coli DNA Polymerases I, II and III with DNA Pol IV in Stressed Cells

Escherichia coli has five DNA polymerases, one of which, the low-fidelity Pol IV or DinB, is required for stress-induced mutagenesis in the well-studied Lac frameshift-reversion assay. Although normally present at ∼200 molecules per cell, Pol IV is recruited to acts of DNA double-strand-break repair, and causes mutagenesis, only when at least two cellular stress responses are activated: the SOS DNA-damage response, which upregulates DinB ∼10-fold, and the RpoS-controlled general-stress response, which upregulates Pol IV about 2-fold. DNA Pol III was also implicated but its role in mutagenesis was unclear. We sought in vivo evidence on the presence and interactions of multiple DNA polymerases during stress-induced mutagenesis. Using multiply mutant strains, we provide evidence of competition of DNA Pols I, II and III with Pol IV, implying that they are all present at sites of stress-induced mutagenesis. Previous data indicate that Pol V is also present. We show that the interactions of Pols I, II and III with Pol IV result neither from, first, induction of the SOS response when particular DNA polymerases are removed, nor second, from proofreading of DNA Pol IV errors by the editing functions of Pol I or Pol III. Third, we provide evidence that Pol III itself does not assist with but rather inhibits Pol IV-dependent mutagenesis. The data support the remaining hypothesis that during the acts of DNA double-strand-break (DSB) repair, shown previously to underlie stress-induced mutagenesis in the Lac system, there is competition of DNA polymerases I, II and III with DNA Pol IV for action at the primer terminus. Up-regulation of Pol IV, and possibly other stress-response-controlled factor(s), tilt the competition in favor of error-prone Pol IV at the expense of more accurate polymerases, thus producing stress-induced mutations. This mutagenesis assay reveals the DNA polymerases operating in DSB repair during stress and also provides a sensitive indicator for DNA polymerase competition and choice in vivo

Living in a machine: Experiencing the world through a robotic avatar

Telepresence has become a main focus of research fuelled by the technological advancements in virtual reality hardware. In this paper we approach telepresence as a collection of sensory modalities and identify what the current state of the art allows with respect to user devices, robotic hardware and the mapping from one to the other

Some considerations in the design and interpretation of antimalarial drug trials in uncomplicated falciparum malaria

BACKGROUND: Treatments for uncomplicated falciparum malaria should have high cure rates. The World Health Organization has recently set a target cure rate of 95% assessed at 28 days. The use of more effective drugs, with longer periods of patient follow-up, and parasite genotyping to distinguish recrudescence from reinfection raise issues related to the design and interpretation of antimalarial treatment trials in uncomplicated falciparum malaria which are discussed here. METHODS: The importance of adequate follow-up is presented and the advantages and disadvantages of non-inferiority trials are discussed. The different methods of interpreting trial results are described, and the difficulties created by loss to follow-up and missing or indeterminate genotyping results are reviewed. CONCLUSION: To characterize cure rates adequately assessment of antimalarial drug efficacy in uncomplicated malaria requires a minimum of 28 days and as much as 63 days follow-up after starting treatment. The longer the duration of follow-up in community-based assessments, the greater is the risk that this will be incomplete, and in endemic areas, the greater is the probability of reinfection. Recrudescence can be distinguished from reinfection using PCR genotyping but there are commonly missing or indeterminate results. There is no consensus on how these data should be analysed, and so a variety of approaches have been employed. It is argued that the correct approach to analysing antimalarial drug efficacy assessments is survival analysis, and patients with missing or indeterminate PCR results should either be censored from the analysis, or if there are sufficient data, results should be adjusted based on the identified ratio of new infections to recrudescences at the time of recurrent parasitaemia. Where the estimated cure rates with currently recommended treatments exceed 95%, individual comparisons with new regimens should generally be designed as non-inferiority trials with sample sizes sufficient to determine adequate precision of cure rate estimates (such that the lower 95% confidence interval bound exceeds 90%)

Population mortality during the outbreak of Severe Acute Respiratory Syndrome in Toronto

<p>Abstract</p> <p>Background</p> <p>Extraordinary infection control measures limited access to medical care in the Greater Toronto Area during the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak. The objective of this study was to determine if the period of these infection control measures was associated with changes in overall population mortality due to causes other than SARS.</p> <p>Methods</p> <p>Observational study of death registry data, using Poisson regression and interrupted time-series analysis to examine all-cause mortality rates (excluding deaths due to SARS) before, during, and after the SARS outbreak. The population of Ontario was grouped into the Greater Toronto Area (N = 2.9 million) and the rest of Ontario (N = 9.3 million) based upon the level of restrictions on delivery of clinical services during the SARS outbreak.</p> <p>Results</p> <p>There was no significant change in mortality in the Greater Toronto Area before, during, and after the period of the SARS outbreak in 2003 compared to the corresponding time periods in 2002 and 2001. The rate ratio for all-cause mortality during the SARS outbreak was 0.99 [95% Confidence Interval (CI) 0.93–1.06] compared to 2002 and 0.96 [95% CI 0.90–1.03] compared to 2001. An interrupted time series analysis found no significant change in mortality rates in the Greater Toronto Area associated with the period of the SARS outbreak.</p> <p>Conclusion</p> <p>Limitations on access to medical services during the 2003 SARS outbreak in Toronto had no observable impact on short-term population mortality. Effects on morbidity and long-term mortality were not assessed. Efforts to contain future infectious disease outbreaks due to influenza or other agents must consider effects on access to essential health care services.</p

Proton-Coupled Electron-Transfer Mechanism for the Radical Scavenging Activity of Cardiovascular Drug Dipyridamole

Dipyridamole (DIP) is a well-known pharmaceutical drug used as a coronary vasodilator and anti-platelet agent in clinics for treating several cardiovascular diseases. Primarily, the therapeutic effects of the drug are attributed to its antioxidant potency. In this research, we aim to declare the unknown antioxidant mechanism of DIP as well as its potent chain-breaking antioxidant activity in polar aqueous medium inside the cells, using different experimental methods and theoretical quantum calculations. Data demonstrated the higher antioxidant capacity of DIP against ROS and free radicals in polar cell's interior. DIP is capable of generating long living and noninvasive DIP• radicals in oxidant condition that leads to an effective “chain-breaking antioxidant” activity. Quantum computational data indicated that DIP antioxidant has more favorable ionization potential than trolox which means DIP has higher antioxidant activity. Also, data showed that the direct hydrogen-transfer is not a favorable process to construct DIP• because of high barrier energy, though electron-transfer process can more easily to produce DIP•+ with the lowest barrier energy. Altogether, the electron donating potency of DIP to reduce ferric ion, having the low anodic oxidation peak potential, producing long lived stable DIP• radicals and protecting myoblast cells from oxidation, proposed the excellent “chain-breaking antioxidant” potency via electron-transfer mechanism of this vasodilator DIP drug in polar aqueous medium

The Role of Interleukin-1 and Interleukin-18 in Pro-Inflammatory and Anti-Viral Responses to Rhinovirus in Primary Bronchial Epithelial Cells

Human Rhinovirus (HRV) is associated with acute exacerbations of chronic respiratory disease. In healthy individuals, innate viral recognition pathways trigger release of molecules with direct anti-viral activities and pro-inflammatory mediators which recruit immune cells to support viral clearance. Interleukin-1alpha (IL-1α), interleukin-1beta (IL-1β) and interleukin-18 (IL-18) have critical roles in the establishment of neutrophilic inflammation, which is commonly seen in airways viral infection and thought to be detrimental in respiratory disease. We therefore investigated the roles of these molecules in HRV infection of primary human epithelial cells. We found that all three cytokines were released from infected epithelia. Release of these cytokines was not dependent on cell death, and only IL-1β and IL-18 release was dependent on caspase-1 catalytic activity. Blockade of IL-1 but not IL-18 signaling inhibited up-regulation of pro-inflammatory mediators and neutrophil chemoattractants but had no effect on virus induced production of interferons and interferon-inducible genes, measured at both mRNA and protein level. Similar level of virus mRNA was detected with and without IL-1RI blockade. Hence IL-1 signaling, potentially involving both IL-1β and IL-1α, downstream of viral recognition plays a key role in induction of pro-inflammatory signals and potentially in recruitment and activation of immune cells in response to viral infection instigated by the epithelial cells, whilst not participating in direct anti-viral responses

Specifying the design for customer learning in the mixed reality experience

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