Computational discovery of electronic materials with structural prediction

This thesis examines structure-property relationships with a focus on two promising chemical areas for conductive applications, copper chalcogenides and lone pair containing materials. At the intersection of these two chemical spaces a structural prediction method is used to examine the Cu-Sn(II)-O ternary space for which no stoichiometric ternary is known. The predicted structures are found to have very high thermodynamic instability to competing phases, and relationships between structure and stability are examined. The same method was used to successfully predict the known structures of SnO and Cu2PbO2. The electronic and optical properties are investigated with ab-initio DFT for a pair of novel earth abundant mixed B-site cation delafossites. The properties of two recently discovered lone pair containing quaternary barium bismuth oxides are investigated and compared with collaborating experimental characterisation. The CuM(2/3)Sb(1/3)O2 (M = Zn/Mg) delafossites are both found to have high valence band effective masses and weak absorption of visible light, moving them away from potential application as photoconversion and p-type conductive materials. M(II) and Sb(V) s state incorporation to the conduction band is found to result in improved conduction band dispersion. Substitution of Nb and Ta into perovskite BaBiO3 is shown to successfully modulate band gaps and produce dispersive valence bands. Ba2BiTaO6 is indicated as a promising transparent conductor due to it's 3.1 eV band gap and high potential p-type mobilities

Telavancin for hospital-acquired pneumonia: Clinical response and 28-day survival

U.S. Food and Drug Administration draft guidance for future antibiotic clinical trials of bacterial nosocomial pneumonia recommends the use of diagnostic criteria according to American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines and the use of a primary endpoint of 28-day all-cause mortality. The effect of applying these guidelines on outcomes of phase III nosocomial pneumonia studies of telavancin was evaluated in a post hoc analysis. ATS/IDSA criteria were applied in a blind fashion to the original all-treated (AT) group. Clinical cure rates at final follow-up were determined in the refined AT and clinically evaluable (CE) groups (ATS/IDSA-AT and ATS/IDSA-CE, respectively). The exploratory endpoint of 28-day survival was evaluated for the ATS/IDSA-AT group. Noninferiority of telavancin versus vancomycin was demonstrated, with similar cure rates in the ATS/IDSA-AT (59% versus 59%) and ATS/IDSA-CE (83% versus 80%) groups. Cure rates favored telavancin in ATS/IDSA-CE patients where Staphylococcus aureus was the sole pathogen (86% versus 75%). Overall, 28-day survival rates were similar in the telavancin (76%) and vancomycin (77%) groups but lower in telavancin-treated patients with preexisting moderate-to-severe renal impairment (creatinine clearance [CL(CR)] of <50 ml/min). Telavancin should be administered to patients with moderate-to-severe renal impairment only if treatment benefit outweighs the risk or if no suitable alternatives are available

Clinical Consensus Conference: Survey on Gram-Positive Bloodstream Infections with a Focus on Staphylococcus aureus

The increased incidence over the past decade of bloodstream infections (BSIs) caused by gram-positive bacteria, particularly methicillin-resistant Staphylococcus aureus , highlights the critical need for a consistent approach to therapy. However, there is currently no international consensus on the diagnosis and management of gram-positive BSIs. The Clinical Consensus Conference on Gram-Positive Bloodstream Infections was convened as a session at the 9th International Symposium on Modern Concepts in Endocarditis and Cardiovascular Infections held in 2007. Participants discussed various aspects of the practical treatment of patients who present with gram-positive BSI, including therapeutic options for patients with BSIs of undefined origin, the selection of appropriate empirical therapy, and treatment of complicated and uncomplicated BSIs. The opinions of participants about these key issues are reflected in this articl

Clinical utility of telavancin for treatment of hospital-acquired pneumonia: focus on non-ventilator-associated pneumonia

BACKGROUND: Hospital-acquired pneumonia (HAP) is the most common health care-associated infection contributing to death. Studies have indicated that there may be differences in the causative pathogens and outcomes of ventilator-associated pneumonia (VAP) and non-ventilator-associated pneumonia (NV-HAP). However, with limited NV-HAP-specific data available, treatment is generally based on data from studies of VAP. The Phase 3 Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia (ATTAIN) studies were two double-blind randomized controlled trials that demonstrated the non-inferiority of telavancin to vancomycin for treatment of Gram-positive HAP. We conducted a post hoc subgroup analysis of patients enrolled in the ATTAIN studies who had NV-HAP. METHODS: Data from the two ATTAIN studies were pooled, and patients with NV-HAP were analyzed. The all-treated (AT) population consisted of all randomized patients who received ≥1 dose of study medication, and the clinically evaluable (CE) population consisted of AT patients who were protocol-adherent or who died on or after study day 3, where death was attributable to the HAP episode under study. The primary endpoint was clinical response (cure, failure, or indeterminate) at the follow-up/test of cure visit, conducted 7–14 days after the end of therapy. RESULTS: A total of 1,076 patients (71.6% of overall ATTAIN AT population) had NV-HAP (533 and 543 patients in the telavancin and vancomycin treatment groups, respectively). Clinical cure rates in the CE population were similar for patients with NV-HAP treated with telavancin and vancomycin (83.1% [201/242] and 84.1% [233/277], respectively). In patients with methicillin-resistant Staphylococcus aureus isolated at baseline, cure rates in the CE population were 74.8% (77/103) for telavancin and 79.3% (96/121) for vancomycin. The incidence of adverse events, serious adverse events, and deaths in patients with NV-HAP was similar whether patients received telavancin or vancomycin. CONCLUSION: This post hoc subgroup analysis of the ATTAIN studies demonstrated similar cure rates for telavancin and vancomycin for treatment of NV-HAP

Chemokine Receptor 5 Δ32 Allele in Patients with Severe Pandemic (H1N1) 2009

Because chemokine receptor 5 (CCR5) may have a role in pulmonary immune response, we explored whether patients with severe pandemic (H1N1) 2009 were more likely to carry the CCR5Δ32 allele than were members of the general population. We found a large proportion of heterozygosity for the CCR5Δ32 allele among white patients with severe disease

Methicillin-resistant Staphylococcus aureus in Neonatal Intensive Care Unit

A neonatal intensive care unit outbreak was caused by a strain of methicillin-resistant Staphylococcus aureus previously found in the community (ST45-MRSA-IV). Fifteen infected neonates were identified, 2 of whom died. This outbreak illustrates how a rare community pathogen can rapidly spread through nosocomial transmission

Genetic Polymorphisms and Drug Susceptibility in Four Isolates of Leishmania tropica Obtained from Canadian Soldiers Returning from Afghanistan

Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease transmitted by the bite of sandflies, resulting in sores on the skin. No vaccines are available, and treatment relies on chemotherapy. CL has been frequently diagnosed in military personnel deployed to Afghanistan and returning from duty. The parasites isolated from Canadian soldiers were characterized by pulsed field gels and by sequencing conserved genes and were identified as Leishmania tropica. In contrast to other Leishmania species, high allelic polymorphisms were observed at several genetic loci for the L. tropica isolates that were characterized. In vitro susceptibility testing in macrophages showed that all isolates, despite their genetic heterogeneity, were sensitive to most antileishmanial drugs (antimonials, miltefosine, amphotericin B, paromomycin) but were insensitive to fluconazole. This study suggests a number of therapeutic regimens for treating cutaneous leishmaniasis caused by L. tropica among patients and soldiers returning from Afghanistan. Canadian soldiers from this study were successfully treated with miltefosine