Aerobic oxidation catalysis with stable radicals

Selective oxidation reactions are challenging when carried out on an industrial scale. Many traditional methods are undesirable from an environmental or safety point of view. There is a need to develop sustainable catalytic approaches that use molecular oxygen as the terminal oxidant. This review will discuss the use of stable radicals (primarily nitroxyl radicals) in aerobic oxidation catalysis. We will discuss the important advances that have occurred in recent years, highlighting the catalytic performance, mechanistic insights and the expanding synthetic utility of these catalytic systems.

Rapid magmatic processes accompany arc-continent collision: the Western Bismarck arc, Papua New Guinea

New U-Th-Ra, major and trace element, and Sr-Nd-Pb isotope data are presented for young lavas from the New Britain and Western Bismarck arcs in Papua New Guinea. New Britain is an oceanic arc, whereas the latter is the site of an arc-continent collision. Building on a recent study of the Manus Basin, contrasts between the two arcs are used to evaluate the processes and timescales of magma generation accompanying arc-continent collision and possible slab detachment. All three suites share many attributes characteristic of arc lavas that can be ascribed to the addition of a regionally uniform subduction component derived from the subducting altered oceanic crust and sediment followed by dynamic melting of the modified mantle. However, the Western Bismarck arc lavas diverge from the Pb isotope mixing array formed by the New Britain and the Manus Basin lavas toward elevated Pb-208/Pb-204. We interpret this to reflect a second and subsequent addition of sediment melt at crustal depth during collision. U-238 and Ra-226 excesses are preserved in all of the lavas and are greatest in the Western Bismarck arc. High-Mg andesites with high Sr/Y ratios in the westernmost arc are attributed to recent shallow mantle flux melting at the slab edge. Data for two historical rhyolites are also presented. Although these rhyolites formed in quite different tectonic settings and display different geochemical and isotopic compositions, both formed from mafic parents within millennia.

Enrichment of pathogenic alleles in the brittle cornea gene, ZNF469, in keratoconus

Keratoconus, a common inherited ocular disorder resulting in progressive corneal thinning, is the leading indication for corneal transplantation in the developed world. Genome-wide association studies have identified common SNPs 100 kb upstream of ZNF469 strongly associated with corneal thickness. Homozygous mutations in ZNF469 and PR domain-containing protein 5 (PRDM5) genes result in brittle cornea syndrome (BCS) Types 1 and 2, respectively. BCS is an autosomal recessive generalized connective tissue disorder associated with extreme corneal thinning and a high risk of corneal rupture. Some individuals with heterozygous PRDM5 mutations demonstrate a carrier ocular phenotype, which includes a mildly reduced corneal thickness, keratoconus and blue sclera. We hypothesized that heterozygous variants in PRDM5 and ZNF469 predispose to the development of isolated keratoconus. We found a significant enrichment of potentially pathologic heterozygous alleles in ZNF469 associated with the development of keratoconus (P = 0.00102) resulting in a relative risk of 12.0. This enrichment of rare potentially pathogenic alleles in ZNF469 in 12.5% of keratoconus patients represents a significant mutational load and highlights ZNF469 as the most significant genetic factor responsible for keratoconus identified to date.

Supported decision making: a review of the international literature

Supported decision making (SDM) refers to the process of supporting people, whose decision making ability may be impaired, to make decisions and so promote autonomy and prevent the need for substitute decision making. There have been developments in SDM but mainly in the areas of intellectual disabilities and end-of-life care rather than in mental health. The main aim of this review was to provide an overview of the available evidence relevant to SDM and so facilitate discussion of how this aspect of law, policy and practice may be further developed in mental health services. The method used for this review was a Rapid Evidence Assessment which involved: developing appropriate search strategies; searching relevant databases and grey literature; then assessing, including and reviewing relevant studies. Included studies were grouped into four main themes: studies reporting stakeholders’ views on SDM; studies identifying barriers to the implementation of SDM; studies highlighting ways to improve implementation; and studies on the impact of SDM. The available evidence on implementation and impact, identified by this review, is limited but there are important rights-based, effectiveness and pragmatic arguments for further developing and researching SDM for people with mental health problems.

The role of adiposity in cardiometabolic traits:a Mendelian randomization analysis

The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.

Seasonal differences in the effects of oscillatory and uni-directional flow on the growth and nitrate-uptake rates of juvenile Laminaria digitata (Phaeophyceae)

The influence of oscillatory versus unidirectional flow on the growth and nitrate-uptake rates of juvenile kelp, Laminaria digitata, was determined seasonally in experimental treatments that simulated as closely as possible natural environmental conditions. In winter, regardless of flow condition (oscillatory and unidirectional) or water velocity, no influence of water motion was observed on the growth rate of L. digitata. In summer, when ambient nitrate concentrations were low, increased water motion enhanced macroalgal growth, which is assumed to be related to an increase in the rate of supply of nutrients to the blade surface. Nitrate-uptake rates were significantly influenced by water motion and season. Lowest nitrate-uptake rates were observed for velocities <5 cm · s−1 and nitrate-uptake rates increased by 20%–50% under oscillatory motion compared to unidirectional flow at the same average speed. These data further suggested that the diffusion boundary layer played a significant role in influencing nitrate-uptake rates. However, while increased nitrate-uptake in oscillatory flow was clear, this was not reflected in growth rates and further work is required to understand the disconnection of nitrate-uptake and growth by L. digitata in oscillatory flow. The data obtained support those from related field-based studies, which suggest that in summer, when insufficient nitrogen is available in the water to saturate metabolic demand, the growth rate of kelps will be influenced by water motion restricting mass transfer of nitrogen.

Mutations in the H, F, or M proteins can facilitate resistance of measles virus to neutralizing human anti-MV sera

Although there is currently no evidence of emerging strains of measles virus (MV) that can resist neutralization by the anti-MV antibodies present in vaccinees, certain mutations in circulating wt MV strains appear to reduce the efficacy of these antibodies. Moreover, it has been hypothesized that resistance to neutralization by such antibodies could allow MV to persist. In this study, we use a novel in vitro system to determine the molecular basis of MV's resistance to neutralization. We find that both wild-type and laboratory strain MV variants that escape neutralization by anti-MV polyclonal sera possess multiple mutations in their H, F, and M proteins. Cytometric analysis of cells expressing viral escape mutants possessing minimal mutations and their plasmid-expressed H, F, and M proteins indicates that immune resistance is due to particular mutations that can occur in any of these three proteins that affect at distance, rather than directly, the native conformation of the MV-H globular head and hence its epitopes. A high percentage of the escape mutants contain mutations found in cases of Subacute Sclerosing Panencephalitis (SSPE) and our results could potentially shed light on the pathogenesis of this rare fatal disease.

Use of SLAM and PVRL4 and Identification of Pro-HB-EGF as Cell Entry Receptors for Wild Type Phocine Distemper Virus

Signalling lymphocyte activation molecule (SLAM) has been identified as an immune cell receptor for the morbilliviruses, measles (MV), canine distemper (CDV), rinderpest and peste des petits ruminants (PPRV) viruses, while CD46 is a receptor for vaccine strains of MV. More recently poliovirus like receptor 4 (PVRL4), also known as nectin 4, has been identified as a receptor for MV, CDV and PPRV on the basolateral surface of polarised epithelial cells. PVRL4 is also up-regulated by MV in human brain endothelial cells. Utilisation of PVRL4 as a receptor by phocine distemper virus (PDV) remains to be demonstrated as well as confirmation of use of SLAM. We have observed that unlike wild type (wt) MV or wtCDV, wtPDV strains replicate in African green monkey kidney Vero cells without prior adaptation, suggesting the use of a further receptor. We therefore examined candidate molecules, glycosaminoglycans (GAG) and the tetraspan proteins, integrin β and the membrane bound form of heparin binding epithelial growth factor (proHB-EGF),for receptor usage by wtPDV in Vero cells. We show that wtPDV replicates in Chinese hamster ovary (CHO) cells expressing SLAM and PVRL4. Similar wtPDV titres are produced in Vero and VeroSLAM cells but more limited fusion occurs in the latter. Infection of Vero cells was not inhibited by anti-CD46 antibody. Removal/disruption of GAG decreased fusion but not the titre of virus. Treatment with anti-integrin β antibody increased rather than decreased infection of Vero cells by wtPDV. However, infection was inhibited by antibody to HB-EGF and the virus replicated in CHO-proHB-EGF cells, indicating use of this molecule as a receptor. Common use of SLAM and PVRL4 by morbilliviruses increases the possibility of cross-species infection. Lack of a requirement for wtPDV adaptation to Vero cells raises the possibility of usage of proHB-EGF as a receptor in vivo but requires further investigation.

Photodynamic antimicrobial polymers for infection control

Hospital-acquired infections pose both a major risk to patient wellbeing and an economic burden on global healthcare systems, with the problem compounded by the emergence of multidrug resistant and biocide tolerant bacterial pathogens. Many inanimate surfaces can act as a reservoir for infection, and adequate disinfection is difficult to achieve and requires direct intervention. In this study we demonstrate the preparation and performance of materials with inherent photodynamic, surface-active, persistent antimicrobial properties through the incorporation of photosensitizers into high density poly(ethylene) (HDPE) using hot-melt extrusion, which require no external intervention except a source of visible light. Our aim is to prevent bacterial adherence to these surfaces and eliminate them as reservoirs of nosocomial pathogens, thus presenting a valuable advance in infection control. A two-layer system with one layer comprising photosensitizer-incorporated HDPE, and one layer comprising HDPE alone is also described to demonstrate the versatility of our approach. The photosensitizer-incorporated materials are capable of reducing the adherence of viable bacteria by up to 3.62 Log colony forming units (CFU) per square centimeter of material surface for methicillin resistant Staphylococcus aureus (MRSA), and by up to 1.51 Log CFU/cm2 for Escherichia coli. Potential applications for the technology are in antimicrobial coatings for, or materials comprising objects, such as tubing, collection bags, handrails, finger-plates on hospital doors, or medical equipment found in the healthcare setting.

Medication use review in Qatar: Are community pharmacists prepared for the extended professional role?

Background
The incidence of chronic illnesses is increasing globally. Non-adherence to medications and other medication-related problems are common among patients receiving long-term medications. Medication use review (MUR) is a service provision with an accredited pharmacist undertaking structured, adherence-centered reviews with patients receiving multiple medications. MUR services are not yet available in community pharmacies in Qatar.

Objective
The current study aims to evaluate community pharmacists' knowledge, attitudes, and perception towards establishing MUR as an extended role in patient care.

Setting
Private community pharmacies in Qatar including chains and independent pharmacies.

Methodology
A cross-sectional survey using a self-administered questionnaire was conducted among licensed community pharmacists from December 2012 to January 2013. Data analysis was conducted using descriptive and inferential statistics.

Main outcome measures
Knowledge, attitudes, and practices related to MUR concept and services.

Results A total of 123 participants responded to the survey (response rate 56 %). The mean total knowledge score was 71.4 ± 14.7 %. An overwhelming proportion of the participants (97 %) were able to identify the scope of MUR in relation to chronic illnesses and at enhancing the quality of pharmaceutical care. Furthermore, 80 % of the respondents were able to identify patients of priority for inclusion in an MUR program. However, only 43 % of the participants knew that acute medical conditions were not the principal focus of an MUR service, while at least 97 % acknowledged that the provision of MUR services is a great opportunity for an extended role of community pharmacists and that MUR makes excellent use of the pharmacist's professional skills in the community. The participants generally reported concerns about time, dedicated consultation area, and support staff as significant barriers towards MUR implementation.

Conclusion
This study suggests that community pharmacists in Qatar had sufficient knowledge about the concept of MUR and its scope, but there were still important deficiencies that warrant further education. The findings have important implications on policy and practice pertaining to the implementation of MUR as an extended role of pharmacists and as part of Qatar's National Health Strategy to move primary health care forward.

Ultrafast Electron Dynamics in Phenylalanine Initiated by Attosecond Pulses

In the last decade attosecond technology has opened up the investigation of ultrafast electronic processes in atoms, simple molecules and solids. Here we report the application of isolated attosecond pulses to prompt ionization of the amino acid phenylalanine, and the subsequent detection of ultrafast dynamics on a sub-4.5-fs temporal scale, which is shorter than the vibrational response of the molecule. The ability to initiate and observe such electronic dynamics in polyatomic molecules represents a crucial step forward in attosecond science, which is progressively moving towards the investigation of more and more complex systems.