Turning the Big Mac Index into the Medical MAC Index

Objective: The purpose of this study was to create a global medical earnings index, called the Medical MAC Index, to enable a comparison of what medical specialists earn in the countries included in the study.Design: The study gathered data on the earnings of specialist anaesthetists employed in state hospitals with five years’ work experience, across 49 developed and developing countries.Setting and subjects: The earnings of anaesthetists were deemed to be indicative of all medical specialities because anaesthesia is one of the largest specialities, and most state hospitals do not distinguish between medical specialities from an earnings perspective. It is likely that a specialist with five years’ work experience would have reached the higher echelons of state salary scales, but it is unlikely that he or she would have moved into a management role yet.Outcome measures: To calculate a Medical MAC Index for a specific country, the net earnings of anaesthetists in the countries included in the study were converted into USA dollars, and adjusted using Xpatulator’s purchasing power parity model, and then compared to the net earnings of an anaesthetist in that specific country. The specific country was the baseline. Countries above the line pay more, and those below the line, less.Results: The Medical MAC Index for South Africa showed that medical specialists employed by the state in South Africa earn more than they would in most developing countries, but their earnings lag behind those of many developed countries.Conclusion: South Africa could become more competitive if tax incentives were used to manipulate the data

Visualizing and trapping transient oligomers in amyloid assembly pathways

Oligomers which form during amyloid fibril assembly are considered to be key contributors towards amyloid disease. However, understanding how such intermediates form, their structure, and mechanisms of toxicity presents significant challenges due to their transient and heterogeneous nature. Here, we discuss two different strategies for addressing these challenges: use of (1) methods capable of detecting lowly-populated species within complex mixtures, such as NMR, single particle methods (including fluorescence and force spectroscopy), and mass spectrometry; and (2) chemical and biological tools to bias the amyloid energy landscape towards specific oligomeric states. While the former methods are well suited to following the kinetics of amyloid assembly and obtaining low-resolution structural information, the latter are capable of producing oligomer samples for high-resolution structural studies and inferring structure-toxicity relationships. Together, these different approaches should enable a clearer picture to be gained of the nature and role of oligomeric intermediates in amyloid formation and disease

Inspiratory muscle warm-up does not improve cycling time-trial performance

Purpose: This study examined the effects of an active cycling warm-up, with and without the addition of an inspiratory muscle warm-up (IMW), on 10-km cycling time-trial performance

Modulation of Amyloidogenic Protein Self-Assembly Using Tethered Small Molecules

Protein–protein interactions (PPIs) are involved in many of life’s essential biological functions yet are also an underlying cause of several human diseases, including amyloidosis. The modulation of PPIs presents opportunities to gain mechanistic insights into amyloid assembly, particularly through the use of methods which can trap specific intermediates for detailed study. Such information can also provide a starting point for drug discovery. Here, we demonstrate that covalently tethered small molecule fragments can be used to stabilize specific oligomers during amyloid fibril formation, facilitating the structural characterization of these assembly intermediates. We exemplify the power of covalent tethering using the naturally occurring truncated variant (ΔN6) of the human protein β2-microglobulin (β2m), which assembles into amyloid fibrils associated with dialysis-related amyloidosis. Using this approach, we have trapped tetramers formed by ΔN6 under conditions which would normally lead to fibril formation and found that the degree of tetramer stabilization depends on the site of the covalent tether and the nature of the protein–fragment interaction. The covalent protein–ligand linkage enabled structural characterization of these trapped, off-pathway oligomers using X-ray crystallography and NMR, providing insight into why tetramer stabilization inhibits amyloid assembly. Our findings highlight the power of “post-translational chemical modification” as a tool to study biological molecular mechanisms

A gentle introduction to the functional renormalization group: the Kondo effect in quantum dots

The functional renormalization group provides an efficient description of the interplay and competition of correlations on different energy scales in interacting Fermi systems. An exact hierarchy of flow equations yields the gradual evolution from a microscopic model Hamiltonian to the effective action as a function of a continuously decreasing energy cutoff. Practical implementations rely on suitable truncations of the hierarchy, which capture nonuniversal properties at higher energy scales in addition to the universal low-energy asymptotics. As a specific example we study transport properties through a single-level quantum dot coupled to Fermi liquid leads. In particular, we focus on the temperature T=0 gate voltage dependence of the linear conductance. A comparison with exact results shows that the functional renormalization group approach captures the broad resonance plateau as well as the emergence of the Kondo scale. It can be easily extended to more complex setups of quantum dots.Comment: contribution to Les Houches proceedings 2006, Springer styl

Inter-domain dynamics in the chaperone SurA and multi-site binding to its outer membrane protein clients

The periplasmic chaperone SurA plays a key role in outer membrane protein (OMP) biogenesis. E. coli SurA comprises a core domain and two peptidylprolyl isomerase domains (P1 and P2), but its mechanisms of client binding and chaperone function have remained unclear. Here, we use chemical cross-linking, hydrogen-deuterium exchange mass spectrometry, single-molecule FRET and molecular dynamics simulations to map the client binding site(s) on SurA and interrogate the role of conformational dynamics in OMP recognition. We demonstrate that SurA samples an array of conformations in solution in which P2 primarily lies closer to the core/P1 domains than suggested in the SurA crystal structure. OMP binding sites are located primarily in the core domain, and OMP binding results in conformational changes between the core/P1 domains. Together, the results suggest that unfolded OMP substrates bind in a cradle formed between the SurA domains, with structural flexibility between domains assisting OMP recognition, binding and release

Maternal effects on anogenital distance in a wild marmot population

Peer reviewedPublisher PD

Effect of thermal treatment on the growth, structure and luminescence of nitride-passivated silicon nanoclusters

Silicon nanoclusters (Si-ncs) embedded in silicon nitride films have been studied to determine the effects that deposition and processing parameters have on their growth, luminescent properties, and electronic structure. Luminescence was observed from Si-ncs formed in silicon-rich silicon nitride films with a broad range of compositions and grown using three different types of chemical vapour deposition systems. Photoluminescence (PL) experiments revealed broad, tunable emissions with peaks ranging from the near-infrared across the full visible spectrum. The emission energy was highly dependent on the film composition and changed only slightly with annealing temperature and time, which primarily affected the emission intensity. The PL spectra from films annealed for duration of times ranging from 2 s to 2 h at 600 and 800°C indicated a fast initial formation and growth of nanoclusters in the first few seconds of annealing followed by a slow, but steady growth as annealing time was further increased. X-ray absorption near edge structure at the Si K- and L3,2-edges exhibited composition-dependent phase separation and structural re-ordering of the Si-ncs and silicon nitride host matrix under different post-deposition annealing conditions and generally supported the trends observed in the PL spectra

The impact of socially-accountable, community-engaged medical education on graduates in the Central Philippines: implications for the global rural medical workforce

Introduction: Developing and retaining a high quality medical workforce, especially within low-resource countries has been a world-wide challenge exacerbated by a lack of medical schools, the maldistribution of doctors towards urban practice, health system inequities, and training doctors in tertiary centers rather than in rural communities. Aim: To describe the impact of socially-accountable health professional education on graduates; specifically: their motivation towards community-based service, preparation for addressing local priority health issues, career choices, and practice location. Methods: Cross-sectional survey of graduates from two medical schools in the Philippines: the University of Manila-School of Health Sciences (SHS-Palo) and a medical school with a more conventional curriculum. Results: SHS-Palo graduates had significantly (p < 0.05) more positive attitudes to community service. SHS-Palo graduates were also more likely to work in rural and remote areas (p < 0.001) either at district or provincial hospitals (p = 0.032) or in rural government health services (p < 0.001) as Municipal or Public Health Officers (p < 0.001). Graduates also stayed longer in both their first medical position (p = 0.028) and their current position (p < 0.001). Conclusions: SHS-Palo medical graduates fulfilled a key aim of their socially-accountable institution to develop a health professional workforce willing and able, and have a commitment to work in underserved rural communties