Deprotection, tethering and activation of a one-legged metalloporphyrin on a chemically active metal surface: NEXAFS, synchrotron XPS and STM study of [SAc]P- Mn(III)Cl on Ag(100)

Abstract The structural and reactive properties of the acetyl-protected "one-legged" manganese porphyrin [SAc]P-Mn(III)Cl on Ag(100) have been studied by NEXAFS, synchrotron XPS and STM. Spontaneous surface-mediated de-protection occurs at 300 K accompanied by spreading of the resulting thio-tethered porphyrin across the metal surface. Loss of the axial chlorine ligand occurs at 498 K, without any de-metallation of the macrocycle, leaving the Mn center in a low co-ordination state. At low coverages the macrocycle is markedly tilted towards the silver surface, as is the phenyl group that forms part of the tethering "leg". In the monolayer region a striking transition occurs whereby the molecule rolls over, preserving the tilt angle of the phenyl group, strongly increasing that of the 2 macrocycle, decreasing the apparent height of the molecule and decreasing its footprint, thus enabling closer packing. These findings are in marked contrast with those previously reported for the corresponding more rigidly bound four-legged porphyrin [JACS 2009[JACS , 126, 1910 suggesting that the physico-chemical properties and potential applications of these versatile systems should be strongly dependent on the mode of tethering to the surface

Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment

Peer reviewedPublisher PD

Metal induced folding: Synthesis and conformational analysis of the lanthanide complexes of two 44-membered hydrazone macrocycles

Six new lanthanide complexes of two 44-membered macrocycles have been prepared and characterised in solution. An analysis of the conformations of the free macrocycles and their lanthanide complexes both in solution (2D NMR) and in solid state (X-ray crystallography) demonstrate that the complexation induces changes in folding of the macrocycles

Common Genetic Variants, Acting Additively, Are a Major Source of Risk for Autism

Background: Autism spectrum disorders (ASD) are early onset neurodevelopmental syndromes typified by impairments in reciprocal social interaction and communication, accompanied by restricted and repetitive behaviors. While rare and especially de novo genetic variation are known to affect liability, whether common genetic polymorphism plays a substantial role is an open question and the relative contribution of genes and environment is contentious. It is probable that the relative contributions of rare and common variation, as well as environment, differs between ASD families having only a single affected individual (simplex) versus multiplex families who have two or more affected individuals. Methods: By using quantitative genetics techniques and the contrast of ASD subjects to controls, we estimate what portion of liability can be explained by additive genetic effects, known as narrow-sense heritability. We evaluate relatives of ASD subjects using the same methods to evaluate the assumptions of the additive model and partition families by simplex/multiplex status to determine how heritability changes with status. Results: By analyzing common variation throughout the genome, we show that common genetic polymorphism exerts substantial additive genetic effects on ASD liability and that simplex/multiplex family status has an impact on the identified composition of that risk. As a fraction of the total variation in liability, the estimated narrow-sense heritability exceeds 60% for ASD individuals from multiplex families and is approximately 40% for simplex families. By analyzing parents, unaffected siblings and alleles not transmitted from parents to their affected children, we conclude that the data for simplex ASD families follow the expectation for additive models closely. The data from multiplex families deviate somewhat from an additive model, possibly due to parental assortative mating. Conclusions: Our results, when viewed in the context of results from genome-wide association studies, demonstrate that a myriad of common variants of very small effect impacts ASD liability

Unstated factors in orthopaedic decision-making: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Total joint replacement (TJR) of the hip or knee for osteoarthritis is among the most common elective surgical procedures. There is some inequity in provision of TJR. How decisions are made about who will have surgery may contribute to disparities in provision. The model of shared decision-making between patients and clinicians is advocated as an ideal by national bodies and guidelines. However, we do not know what happens within orthopaedic practice and whether this reflects the shared model. Our study examined how decisions are made about TJR in orthopaedic consultations.</p> <p>Methods</p> <p>The study used a qualitative research design comprising semi-structured interviews and observations. Participants were recruited from three hospital sites and provided their time free of charge. Seven clinicians involved in decision-making about TJR were approached to take part in the study, and six agreed to do so. Seventy-seven patients due to see these clinicians about TJR were approached to take part and 26 agreed to do so. The patients' outpatient appointments ('consultations') were observed and audio-recorded. Subsequent interviews with patients and clinicians examined decisions that were made at the appointments. Data were analysed using thematic analysis.</p> <p>Results</p> <p>Clinical and lifestyle factors were central components of the decision-making process. In addition, the roles that patients assigned to clinicians were key, as were communication styles. Patients saw clinicians as occupying expert roles and they deferred to clinicians' expertise. There was evidence that patients modified their behaviour within consultations to complement that of clinicians. Clinicians acknowledged the complexity of decision-making and provided descriptions of their own decision-making and communication styles. Patients and clinicians were aware of the use of clinical and lifestyle factors in decision-making and agreed in their description of clinicians' styles. Decisions were usually reached during consultations, but patients and clinicians sometimes said that treatment decisions had been made beforehand. Some patients expressed surprise about the decisions made in their consultations, but this did not necessarily imply dissatisfaction.</p> <p>Conclusions</p> <p>The way in which roles and communication are played out in decision-making for TJR may affect the opportunity for shared decisions. This may contribute to variation in the provision of TJR. Making the importance of these factors explicit and highlighting the existence of patients' 'surprise' about consultation outcomes could empower patients within the decision-making process and enhance communication in orthopaedic consultations.</p

Compendium of Single Event Effects Results for Candidate Spacecraft Electronics for NASA

Susceptibility of a variety of candidate spacecraft electronics to proton and heavy ion induced single event effects is studied. Devices tested include digital, linear bipolar, and hybrid devices

De novo mutations in histone modifying genes in congenital heart disease

Congenital heart disease (CHD) is the most frequent birth defect, affecting 0.8% of live births1. Many cases occur sporadically and impair reproductive fitness, suggesting a role for de novo mutations. By analysis of exome sequencing of parent-offspring trios, we compared the incidence of de novo mutations in 362 severe CHD cases and 264 controls. CHD cases showed a significant excess of protein-altering de novo mutations in genes expressed in the developing heart, with an odds ratio of 7.5 for damaging mutations. Similar odds ratios were seen across major classes of severe CHD. We found a marked excess of de novo mutations in genes involved in production, removal or reading of H3K4 methylation (H3K4me), or ubiquitination of H2BK120, which is required for H3K4 methylation2–4. There were also two de novo mutations in SMAD2; SMAD2 signaling in the embryonic left-right organizer induces demethylation of H3K27me5. H3K4me and H3K27me mark `poised' promoters and enhancers that regulate expression of key developmental genes6. These findings implicate de novo point mutations in several hundred genes that collectively contribute to ~10% of severe CHD

Use Of Medical Tourism For Hip And Knee Surgery In Osteoarthritis: A Qualitative Examination Of Distinctive Attitudinal Characteristics Among Canadian Patients

Background Medical tourism is the term that describes patients’ international travel with the intention of seeking medical treatment. Some medical tourists go abroad for orthopaedic surgeries, including hip and knee resurfacing and replacement. In this article we examine the findings of interviews with Canadian medical tourists who went abroad for such surgeries to determine what is distinctive about their attitudes when compared to existing qualitative research findings about patients’ decision-making in and experiences of these same procedures in their home countries. Methods Fourteen Canadian medical tourists participated in semi-structured phone interviews, all of whom had gone abroad for hip or knee surgery to treat osteoarthritis. Transcripts were coded and thematically analysed, which involved comparing emerging findings to those in the existing qualitative literature on hip and knee surgery. Results Three distinctive attitudinal characteristics among participants were identified when interview themes were compared to findings in the existing qualitative research on hip and knee surgery in osteoarthritis. These attitudinal characteristics were that the medical tourists we spoke with were: (1) comfortable health-related decision-makers; (2) unwavering in their views about procedure necessity and urgency; and (3) firm in their desires to maintain active lives. Conclusions Compared to other patients reported on in the existing qualitative hip and knee surgery literature, medical tourists are less likely to question their need for surgery and are particularly active in their pursuit of surgical intervention. They are also comfortable with taking control of health-related decisions. Future research is needed to identify motivators behind patients’ pursuit of care abroad, determine if the attitudinal characteristics identified here hold true for other patient groups, and ascertain the impact of these attitudinal characteristics on surgical outcomes. Arthritis care providers can use the attitudinal characteristics identified here to better advise osteoarthritis patients who are considering seeking care abroad