Protein-mediated dethreading of a biotin-functionalised pseudorotaxane

In this article, we describe the synthesis of new biotin-functionalised naphthalene derivatives 3 and 4 and their complexation behaviour with avidin and neutravidin using a range of analytical techniques. We have shown using 2-(4prime or minute-hydroxyazobenzene)benzoic acid displacement and ITC experiments{,} that compounds 3 and 4 have the propensity to form reasonably high-affinity bioconjugates with avidin and neutravidin. We have also demonstrated using 1H NMR{,} UV-vis and fluorescence spectroscopy that the naphthalene moiety of 3 and 4 facilitates the formation of pseudorotaxane-like structures with 1 in water. We have then investigated the ability of avidin and neutravidin to modulate the complexation between 1 and 3 or 4. UV-vis and fluorescence spectroscopy has shown that in both cases the addition of the protein disrupts complexation between the naphthalene moieties of 3 and 4 with 1

Reexamining evidence-based practice in community corrections: beyond 'a confined view' of what works

This article aims to reexamine the development and scope of evidence-based practice (EBP) in community corrections by exploring three sets of issues. Firstly, we examine the relationships between the contested purposes of community supervision and their relationships to questions of evidence. Secondly, we explore the range of forms of evidence that might inform the pursuit of one purpose of supervision—the rehabilitation of offenders—making the case for a fuller engagement with “desistance” research in supporting this process. Thirdly, we examine who can and should be involved in conversations about EBP, arguing that both ex/offenders’ and practitioners’ voices need to be respected and heard in this debate

Ab initio calculation of the neutron-proton mass difference

The existence and stability of atoms rely on the fact that neutrons are more massive than protons. The measured mass difference is only 0.14\% of the average of the two masses. A slightly smaller or larger value would have led to a dramatically different universe. Here, we show that this difference results from the competition between electromagnetic and mass isospin breaking effects. We performed lattice quantum-chromodynamics and quantum-electrodynamics computations with four nondegenerate Wilson fermion flavors and computed the neutron-proton mass-splitting with an accuracy of $300$ kilo-electron volts, which is greater than $0$ by $5$ standard deviations. We also determine the splittings in the $\Sigma$, $\Xi$, $D$ and $\Xi_{cc}$ isospin multiplets, exceeding in some cases the precision of experimental measurements.Comment: 57 pages, 15 figures, 6 tables, revised versio

Hormonal impact of the 17α-hydroxylase/C17,20-lyase inhibitor abiraterone acetate (CB7630) in patients with prostate cancer

A series of three dose escalating studies were conducted to investigate the ability of the 17-hydroxylase/C17,20-lyase inhibitor abiraterone acetate, to cause maximum suppression of testosterone synthesis when delivered to castrate and noncastrate males with prostate cancer. Study A was a single dose study in castrate males. Study B was a single dose study in noncastrate males and study C was a multiple dose study in noncastrate males. The drug was given orally in a once-daily dose and blood samples taken to assess pharmacokinetic (PK) parameters and hormone levels in all patients. The study drug was well tolerated with some variability in PKs. Suppression of testosterone levels to <0.14 nmol l-1 was seen in four out of six castrate males treated with a single dose of 500 mg. At 800 mg given days 1–12 in noncastrate males, target suppression was achieved in three out of three patients, but a two- to three-fold increase of Luteinising Hormone (LH) levels in two out of three patients overcame suppression within 3 days. All patients in the multiple dose study developed an abnormal response to a short Synacthen test by day 11, although baseline cortisol levels remained normal. This is the first report of the use of a specific 17-hydroxylase/17,20-lyase inhibitor in humans. Repeated treatment of men with intact gonadal function with abiraterone acetate at a dose of 800 mg can successfully suppress testosterone levels to the castrate range. However, this level of suppression may not be sustained in all patients due to compensatory hypersecretion of LH. The enhanced testosterone suppression achieved in castrate men merits further clinical study as a second-line hormonal treatment for prostate cancer. Adrenocortical suppression may necessitate concomitant administration of replacement glucocorticoid

Pathways to “Evidence-Informed” Policy and Practice: A Framework for Action

Bowen and Zwi propose a new framework that can help researchers and policy makers to navigate the use of evidence

Obstacle crossing among people with Parkinson disease is influenced by concurrent music

Open accessMultitasking situations exacerbate gait impairments and increase the risk of falling among people with Parkinson disease (PD). This study compared obstacle negotiation among 10 subjects with PD and 10 nonparkinsonian control (CTRL) subjects in two test conditions differentiated by the presence of music played through a personal music player. Subjects walked the length of a 10 m walkway at a self-selected pace, crossing a 0.15 m obstacle placed at the midpoint of the walkway. The results indicated that subjects with PD crossed the obstacle slower than CTRL subjects and that concurrent music differentially altered obstacle crossing behaviors for the CTRL subjects and subjects with PD. Subjects with PD further decreased obstacle-crossing velocities and maintained spatial parameters in the music condition. In contrast, CTRL subjects maintained all spatiotemporal parameters of obstacle crossing with music. The alterations to crossing behaviors observed among the subjects with PD support our previous suggestion that listening to music while walking may be an attentionally demanding task.Ye

Hole depletion and localization due to disorder in insulating PrBa2Cu3O7-d: a Compton scattering study

The (mostly) insulating behaviour of PrBa2Cu3O7-d is still unexplained and even more interesting since the occasional appearance of superconductivity in this material. Since YBa2Cu3O7-d is nominally iso-structural and always superconducting, we have measured the electron momentum density in these materials. We find that they differ in a striking way, the wavefunction coherence length in PrBa2Cu3O7-d being strongly suppressed. We conclude that Pr on Ba-site substitution disorder is responsible for the metal-insulator transition. Preliminary efforts at growth with a method to prevent disorder yield 90K superconducting PrBa2Cu3O7-d crystallites.Comment: 4 pages, 3 figures, revised version submitted to PR

Using research to influence sexual and reproductive health practice and implementation in Sub-Saharan Africa: a case-study analysis

Background Research institutions and donor organizations are giving growing attention to how research evidence is communicated to influence policy. In the area of sexual and reproductive health (SRH) and HIV there is less weight given to understanding how evidence is successfully translated into practice. Policy issues in SRH can be controversial, influenced by political factors and shaped by context such as religion, ethnicity, gender and sexuality. Methods The case-studies presented in this paper analyse findings from SRH/HIV research programmes in sub-Saharan Africa: 1) Maternal syphilis screening in Ghana, 2) Legislative change for sexual violence survivors In Ghana, 3) Male circumcision policy in South Africa, and 4) Male circumcision policy in Tanzania. Our analysis draws on two frameworks, Sumner et al’s synthesis approach and Nutley’s research use continuum. Results The analysis emphasises the relationships and communications involved in using research to influence policy and practice and recognises a distinction whereby practice is not necessarily influenced as a result of policy change – especially in SRH – where there are complex interactions between policy actors. Conclusion Both frameworks demonstrate how policy networks, partnership and advocacy are critical in shaping the extent to which research is used and the importance of on-going and continuous links between a range of actors to maximize research impact on policy uptake and implementation. The case-studies illustrate the importance of long-term engagement between researchers and policy makers and how to use evidence to develop policies which are sensitive to context: political, cultural and practical

Effects of gestational age at birth on cognitive performance : a function of cognitive workload demands

Objective: Cognitive deficits have been inconsistently described for late or moderately preterm children but are consistently found in very preterm children. This study investigates the association between cognitive workload demands of tasks and cognitive performance in relation to gestational age at birth. Methods: Data were collected as part of a prospective geographically defined whole-population study of neonatal at-risk children in Southern Bavaria. At 8;5 years, n = 1326 children (gestation range: 23–41 weeks) were assessed with the K-ABC and a Mathematics Test. Results: Cognitive scores of preterm children decreased as cognitive workload demands of tasks increased. The relationship between gestation and task workload was curvilinear and more pronounced the higher the cognitive workload: GA2 (quadratic term) on low cognitive workload: R2 = .02, p<0.001; moderate cognitive workload: R2 = .09, p<0.001; and high cognitive workload tasks: R2 = .14, p<0.001. Specifically, disproportionally lower scores were found for very (<32 weeks gestation) and moderately (32–33 weeks gestation) preterm children the higher the cognitive workload of the tasks. Early biological factors such as gestation and neonatal complications explained more of the variance in high (12.5%) compared with moderate (8.1%) and low cognitive workload tasks (1.7%). Conclusions: The cognitive workload model may help to explain variations of findings on the relationship of gestational age with cognitive performance in the literature. The findings have implications for routine cognitive follow-up, educational intervention, and basic research into neuro-plasticity and brain reorganization after preterm birth