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We review recent experiments in which superfluid $$^3$$ He has been studied under highly controlled confinement in nanofluidic sample chambers. We discuss the experimental challenges and their resolution. These methods open the way to a systematic investigation of the superfluidity of $$^3$$ He films, and the surface and edge excitations of topological superfluids.

BackgroundSexually transmitted infection (STI) diagnoses are increasing and efforts to reduce transmission have failed. There are major uncertainties in the evidence base surrounding the delivery of STI care for men.AimTo improve the sexual health of young men in the UK by determining optimal strategies for STI testing and careObjectivesTo develop an evidence-based clinical algorithm for STI testing in asymptomatic men; model mathematically the epidemiological and economic impact of removing microscopy from routine STI testing in asymptomatic men; conduct a pilot randomised controlled trial (RCT) of accelerated partner therapy (APT; new models of partner notification to rapidly treat male sex partners of people with STIs) in primary care; explore the acceptability of diverse venues for STI screening in men; and determine optimal models for the delivery of screening.DesignSystematic review of the clinical consequences of asymptomatic non-chlamydial, non-gonococcal urethritis (NCNGU); case–control study of factors associated with NCNGU; mathematical modelling of the epidemiological and economic impact of removing microscopy from asymptomatic screening and cost-effectiveness analysis; pilot RCT of APT for male sex partners of women diagnosed withChlamydia trachomatisinfection in primary care; stratified random probability sample survey of UK young men; qualitative study of men’s views on accessing STI testing; SPORTSMART pilot cluster RCT of two STI screening interventions in amateur football clubs; and anonymous questionnaire survey of STI risk and previous testing behaviour in men in football clubs.SettingsGeneral population, genitourinary medicine clinic attenders, general practice and community contraception and sexual health clinic attenders and amateur football clubs.ParticipantsMen and women.InterventionsPartner notification interventions: APTHotline [telephone assessment of partner(s)] and APTPharmacy [community pharmacist assessment of partner(s)]. SPORTSMART interventions: football captain-led and health adviser-led promotion of urine-based STI screening.Main outcome measuresFor the APT pilot RCT, the primary outcome, determined for each contactable partner, was whether or not they were considered to have been treated within 6 weeks of index diagnosis. For the SPORTSMART pilot RCT, the primary outcome was the proportion of eligible men accepting screening.ResultsNon-chlamydial, non-gonococcal urethritis is not associated with significant clinical consequences for men or their sexual partners but study quality is poor (systematic review). Men with symptomatic and asymptomatic NCNGU and healthy men share similar demographic, behavioural and clinical variables (case–control study). Removal of urethral microscopy from routine asymptomatic screening is likely to lead to a small rise in pelvic inflammatory disease (PID) but could save > £5M over 20 years (mathematical modelling and health economics analysis). In the APT pilot RCT the proportion of partners treated by the APTHotline [39/111 (35%)], APTPharmacy [46/100 (46%)] and standard patient referral [46/102 (45%)] did not meet national standards but exceeded previously reported outcomes in community settings. Men’s reported willingness to access self-sampling kits for STIs and human immunodeficiency virus infection was high. Traditional health-care settings were preferred but sports venues were acceptable to half of men who played sport (random probability sample survey). Men appear to prefer a ‘straightforward’ approach to STI screening, accessible as part of their daily activities (qualitative study). Uptake of STI screening in the SPORTSMART RCT was high, irrespective of arm [captain led 28/56 (50%); health-care professional led 31/46 (67%); poster only 31/51 (61%)], and costs were similar. Men were at risk of STIs but previous testing was common.ConclusionsMen find traditional health-care settings the most acceptable places to access STI screening. Self-sampling kits in football clubs could widen access to screening and offer a public health impact for men with limited local sexual health services. Available evidence does not support an association between asymptomatic NCNGU and significant adverse clinical outcomes for men or their sexual partners but the literature is of poor quality. Similarities in characteristics of men with and without NCNGU precluded development of a meaningful clinical algorithm to guide STI testing in asymptomatic men. The mathematical modelling and cost-effectiveness analysis of removing all asymptomatic urethral microscopy screening suggests that this would result in a small rise in adverse outcomes such as PID but that it would be highly cost-effective. APT appears to improve outcomes of partner notification in community settings but outcomes still fail to meet national standards. Priorities for future work include improving understanding of men’s collective behaviours and how these can be harnessed to improve health outcomes; exploring barriers to and facilitators of opportunistic STI screening for men attending general practice, with development of evidence-based interventions to increase the offer and uptake of screening; further development of APT for community settings; and studies to improve knowledge of factors specific to screening men who have sex with men (MSM) and, in particular, how, with the different epidemiology of STIs in MSM and the current narrow focus on chlamydia, this could negatively impact MSM’s sexual health.FundingThe National Institute for Health Research Programme Grants for Applied Research programme.

This paper reports on the results achieved within the European Metrology Research Programme project “Implementing the new kelvin—InK” in the low-temperature range below 1 K. One of the main objectives of the InK project was the determination of new thermodynamic temperature data for comparison with the Provisional Low Temperature Scale 2000 (PLTS-2000), to provide reliable $$T-T_{2000}$$ values. To this end, we have investigated three different types of primary thermometers: the current sensing noise thermometer, the primary magnetic field fluctuation thermometer and the Coulomb blockade thermometer. Based on a thorough investigation of the thermometers, detailed uncertainty budgets were established for the measurement of thermodynamic temperatures. Direct comparison measurements between all thermometers demonstrate the agreement of temperature measurements within less than 1 %. Our new $$T-T_{2000}$$ data confirm the correctness of the PLTS-2000 in the temperature range from 20 mK up to about 700 mK with relative combined standard uncertainties better than 0.62 %.

In this letter we describe the observation of a magnetic field dependent electronic gap, suggestive of local superconductivity, in the point-contact spectrum of micro-crystalline graphite. Magnetic field dependent point-contact spectroscopy was carried out at a temperature of $1.8\,\mathrm{K}$ using an etched aluminium tip. At zero field a gap structure in the differential conductance is observed, showing a gap of $\Delta = 4.2\,\mathrm{meV}$. On applying magnetic fields of up to $500\,\mathrm{mT}$, this gap gradually closes, following the theoretical prediction by Ginzburg and Landau for a fully flux-penetrated superconductor. By applying BCS-theory, we infer a critical superconducting temperature of $14\,\mathrm{K}$.

Summary The significance of asymptomatic non-chlamydial non-gonococcal urethritis (NCNGU) is unclear. Organisms associated with NCNGU, e.g. Mycoplasma genitalium, for which there is no widely available test, are linked to reproductive sequelae in women but UK guidance no longer recommends urethral smear microscopy to screen for asymptomatic NCNGU. This case-control study of heterosexual male genitourinary (GU) medicine clinic attenders aimed to identify clinical, demographic and sexual behaviour factors associated with asymptomatic NCNGU so that we could determine whether the presence or absence of symptoms provides a rational basis for deciding to whom we should offer microscopy and whom we should treat. Men with asymptomatic NCNGU were very similar to men with symptomatic NCNGU, except for more consistent condom use. Asymptomatic and symptomatic NCNGU could be different ends of the same clinical syndrome. Until the microbiological basis of NCNGU is understood, we recommend treatment of men with NCNGU irrespective of symptoms.

a b s t r a c t We report a chemical vapor sensor in which polymer swelling, upon analyte absorption, is used to deform an on-chip silicon Fabry-Perot interferometer (FPI). The magnitude of the deformation, recorded through the resonance wavelength shift, is proportional to the analyte concentration in accordance with a simplified analytical model and with finite element simulations. Conventional and phenyl-doped poly- dimethylsiloxane (PDMS) polymers are used to functionalize different interferometers, which are tested for the detection of two volatile organic compounds, i.e. m-xylene and cyclohexane. The detection of m-xylene concentrations down to 34 ppm—limited by our flow-meter setup—is achieved experimen- tally. Based on the sensitivities and the noise characteristics of the devices, limits of detection (LODs) of 1.6 ppm m-xylene and 6.3 ppm cyclohexane are expected.

The motivation for this study was to explore a conceptual framework to understand the outcomes and processes of motor performance in children. Vertical jumping, a fundamental movement skill, was used to compare children (ages 6–12 years) who were typically developing (TD) and those identified as having low motor proficiency (LMP). Jumps were analysed using force plate and 2D kinematic data. The hierarchal framework was applied starting with jump height and descending to the spatial and timing data that describe the global and local coordination processes. Children with LMP jumped lower than their TD peers. Of most interest for understanding the coordination, peak VCOM occurred earlier in the jumping movement for the LMP group. This is interpreted as coordination error and supported by reduced shank angular velocity immediately prior to take-off. These findings suggest a potential value for the vertical jump as a means for identifying coordination dysfunction in children.

The chemokine receptor CCR2 is a G protein-coupled receptor that is activated primarily by the endogenous CC chemokine ligand 2 (CCL2). Many different small-molecule antagonists have been developed to inhibit this receptor, as it is involved in a variety of diseases characterized by chronic inflammation. Unfortunately, all these antagonists lack clinical efficacy, and therefore a better understanding of their mechanism of action is warranted. In this study, we examined the pharmacological properties of small-molecule CCR2 antagonists in radioligand binding and functional assays. Six structurally different antagonists were selected for this study, all of which displaced the endogenous agonist (125)I-CCL2 from CCR2 with nanomolar affinity. Two of these antagonists, INCB3344 [N-(2-(((3S,4S)-1-((1r,4S)-4-(benzo[d][1,3]dioxol-5-yl)-4-hydroxycyclohexyl)-4-ethoxypyrrolidin-3-yl)amino)-2-oxoethyl)-3-(trifluoromethyl)benzamide] and CCR2-RA, were radiolabeled to study the binding site in greater detail. We discovered that [(3)H]INCB3344 and [(3)H]CCR2-RA bind to distinct binding sites at CCR2, the latter being the first allosteric radioligand for CCR2. Besides the binding properties of the antagonists, we examined CCR2 inhibition in multiple functional assays, including a novel label-free whole-cell assay. INCB3344 competitively inhibited CCL2-induced G protein activation, whereas CCR2-RA showed a noncompetitive or allosteric mode of inhibition. These findings demonstrated that the CCR2 antagonists examined in this study can be classified into two groups with different binding sites and thereby different modes of inhibition. We have provided further insights in CCR2 antagonism, and these insights are important for the development of novel CCR2 inhibitors.

See Change is Ireland’s national programme working to positively change social attitudes and behaviour so that there is a reduction of stigma and discrimination associated with mental health problems, ensuring that everyone in Ireland enjoys the same rights on an equal basis. See Change works within a number of interrelated settings: finding the conversation, joining in and working with people and communities on the ground. This is Ireland’s first ever national stigma reduction partnership and exists to inspire a disruptive social movement in Ireland to reduce the stigma and discrimination of mental health problems so that mental health problems are viewed as part and parcel of being human – in the workplace, at home, out and about, in the media and everywhere else.

Side-chain cyclic sulphates derived from a δ-lactone (1) provide easy access to complex tetrahydrofuran, tetrahydropyran and cyclohexane derivatives each with 5 adjacent chiral centres and at least 6 adjacent carbons bearing functional groups.

The contour lithography method [1] is used to improve the fabrication yield of previously demonstrated [2] microfluidic Fabry-Perot (FP) refractive index (RI) sensors. The sensors are then coated with polydimethylsiloxane (PDMS) based polymers to detect vapor analytes by solid-phase microextraction (SPME). Preliminary characterization of devices coated with two different polymers and exposed to xylenes vapors yields a maximum sensitivity of 0.015 nm/ppm and a detection limit below 120 ppm.

We report a method for real-time monitoring of vapor uptake by simultaneous detection of the refractive index, 𝑛 , and thickness, 𝑑 , of thin transparent films with a precision of 𝛿𝑛=10 −4 and 𝛿𝑑

Using a large-angle refractometer, the refractive indices of water, methanol, acetonitrile, acetone, ethanol, formaldehyde solution, 2-propanol, hexanes, 1-propanol, 2-butanol, tetrahydrofuran, dichloromethane, 1,4-dioxane, cyclohexane, N,N-dimethylformamide, ethylene glycol, N,N-dimethylacetamide, chloroform, glycerol, trichloroethylene, dimethylsulfoxide, p-xylene, ethylbenzene, toluene, m-xylene, benzene, and o-xylene were measured at 1550 nm and compared to literature values. In addition, the refractive indices of 48 aqueous sucrose solutions, 34 aqueous sodium chloride solutions, 40 DMSO-water, 40 ethylene glycol-water, and 40 glycerol-water mixtures were also measured at different concentrations and fit with third-order polynomial expressions. This study provides near-infrared refractive indices that were not previously available and may help with the calibration of refractive index sensors that operate at or near 1550 nm.

Trace level lead Pb(II) to parts per billion (ppb) in water was detected using silicon-on-insulator (SOI) microresonators. The SOI microchips were coated with tetrasulfide functionalized mesoporous silicates.

The use of low-temperature platforms with base temperatures below 1 K is rapidly expanding, for fundamental science, sensitive instrumentation and new technologies of potentially significant commercial impact. Precise measurement of the thermodynamic temperature of these low-temperature platforms is crucial for their operation. In this paper, we describe a practical and user-friendly primary current-sensing noise thermometer (CSNT) for reliable and traceable thermometry and the dissemination of the new kelvin in this temperature regime. Design considerations of the thermometer are discussed, including the optimization of a thermometer for the temperature range to be measured, noise sources and thermalization. We show the procedure taken to make the thermometer primary and contributions to the uncertainty budget. With standard laboratory instrumentation, a relative uncertainty of 1.53% is obtainable. Initial comparison measurements between a primary CSNT and a superconducting reference device traceable to the PLTS-2000 (Provisional Low Temperature Scale of 2000) are presented between 66 and 208 mK, showing good agreement within the k =1 calculated uncertainty.

We describe a simple large-angle interferometer that permits the independent measurements of thickness and refractive index of films in the 20-200 micron thickness range at a 10Hz DAQ rate.

The influence of confinement on the topological phases of superfluid 3He is studied using the torsional pendulum method. We focus on the phase transition between the chiral A-phase and the time-reversal-invariant B-phase, motivated by the prediction of a spatiallymodulated (stripe) phase at the A-B phase boundary. We confine superfluid 3He to a single 1.08 {\mu}m thick nanofluidic cavity incorporated into a high-precision torsion pendulum, and map the phase diagram between 0.1 and 5.6 bar. We observe only small supercooling of the A-phase, in comparison to bulk or when confined in aerogel. This has a non-monotonic pressure dependence, suggesting that a new intrinsic B-phase nucleation mechanism operates under confinement, mediated by the putative stripe phase. Both the phase diagram and the relative superfluid fraction of the A and B phases, show that strong coupling is present at all pressures, with implications for the stability of the stripe phase., Comment: 6 figures, 1 table + supplemental information

Infection is a leading cause of morbidity and mortality among haemodialysis patients. Some of the risk factors specific to this population include repeated access to the blood stream through venous cannulation for dialysis as well as a higher prevalent usage of prosthetic materials like haemodialysis catheters and arteriovenous grafts. In addition, defects in immunity and phagocytosis also contribute to the increased risk of infection. Both iron overload [1] and its treatment, desferrioxamine (DFO), predispose haemodialysis patients to infections [2, 3]. We describe here a fatal case of Cunninghamella bertholletiae infection in a haemodialysis patient with transfusional iron overload while receiving DFO.

Objectives Rates of sexually transmitted infections (STIs) in UK young people remain high in men and women. However, the National Chlamydia Screening Programme has had limited success in reaching men. The authors explored the acceptability of various medical, recreational and sports venues as settings to access self-collected testing kits for STIs and HIV among men in the general population and those who participate in sport. Methods A stratified random probability survey of 411 (weighted n¼632) men in Great Britain aged 18e35 years using computer-assisted personal and self-interviews. Results Young men engaged well with healthcare with 93.5% registered with, and 75.3% having seen, a general practitioner in the last year. 28.7% and 19.8% had previously screened for STIs and HIV, respectively. Willingness to access self-collected tests for STIs (85.1%) and HIV (86.9%) was high. The most acceptable pick-up points for testing kits were general practice 79.9%, GUM 66.8% and pharmacy 65.4%. There was a low acceptability of sport venues as pick-up points in men as a whole (11.7%), but this was greater among those who participated in sport (53.9%). Conclusions Healthcare settings were the most acceptable places for accessing STI and HIV self-testing kits. Although young men frequently access general practice, currently little STI screening occurs in this setting. There is considerable potential to screen large numbers of men and find high rates of infection through screening in general practice. While non-clinical settings are acceptable to a minority of men, more research is needed to understand how these venues could be used most effectively.

The uptake and release of sorbates into films and coatings is typically accompanied by changes of the films' refractive index and thickness. We provide a comprehensive model to calculate the concentration of the sorbate from the average refractive index and the film thickness, and validate the model experimentally. The mass fraction of the analyte partitioned into a film is described quantitatively by the Lorentz-Lorenz equation and the Clausius-Mosotti equation. To validate the model, the uptake kinetics of water and other solvents into SU-8 films (d = 40-45 μm) were explored. Large-angle interferometric refractometry measurements can be used to characterize films that are between 15 μm to 150 μm thick and, Fourier analysis, is used to determine independently the thickness, the average refractive index and the refractive index at the film-substrate interface at one-second time intervals. From these values the mass fraction of water in SU-8 was calculated. The kinetics were best described by two independent uptake processes having different rates. Each process followed one-dimensional Fickian diffusion kinetics with diffusion coefficients for water into SU-8 photoresist film of 5.67 × 10(-9) cm(2) s(-1) and 61.2 × 10(-9) cm(2) s(-1).

There is contrast between the surge in the quality of business and management research reported in successive Research Assessment Exercises and Britain's inconsistent contribution to the world's leading business and management journals over the last 40 years. A census of top journals since 1968 shows a relative decline of the English-speaking peoples and a rise in the contribution from parts of Southeast Asia and northern Europe. Unlike the USA and the euro-area, where the top researchers are mainly born and research trained in their own country, the UK's leading business and management researchers tend to be non-locals trained outside the UK.

In the present study, the diversity of a library of drug-metabolizing bacterial cytochrome P450 (P450) BM3 mutants was evaluated by a liquid chromatography-mass spectrometry (LC-MS)-based screening method. A strategy was designed to identify a minimal set of BM3 mutants that displays differences in regio- and stereoselectivities and is suitable to metabolize a large fraction of drug chemistry space. We first screened the activities of six structurally diverse BM3 mutants toward a library of 43 marketed drugs (encompassing a wide range of human P450 phenotypes, cLogP values, charges, and molecular weights) using a rapid LC-MS method with an automated method development and data-processing system. Significant differences in metabolic activity were found for the mutants tested and based on this drug library screen; nine structurally diverse probe drugs were selected that were subsequently used to study the metabolism of a library of 14 BM3 mutants in more detail. Using this alternative screening strategy, we were able to select a minimal set of BM3 mutants with high metabolic activities and diversity with respect to substrate specificity and regiospecificity that could produce both human relevant and BM3 unique drug metabolites. This panel of four mutants (M02, MT35, MT38, and MT43) was capable of producing P450-mediated metabolites for 41 of the 43 drugs tested while metabolizing 77% of the drugs by more than 20%. We observed this as the first step in our approach to use of bacterial P450 enzymes as general reagents for lead diversification in the drug development process and the biosynthesis of drug(-like) metabolites.

Opinions are divided on whether to screen asymptomatic men for non-chlamydial non-gonococcal urethritis (NCNGU). We systematically reviewed the literature to determine whether male asymptomatic NCNGU is associated with significant clinical outcomes for men and/or their sexual partners. We searched electronic databases and reference lists from retrieved articles and reviews. No studies reporting clinical outcomes in men with asymptomatic NCNGU were identified. Two eligible studies report rates of sexually transmitted infections (STIs) in female partners of men with asymptomatic NCNGU; Chlamydia trachomatis was detected in 2.4% and 8.3% of these women. The evidence available is insufficient in quality and breadth to enable us to conclude whether asymptomatic NCNGU is associated with significant health consequences for men or their sexual partners; however, clinical consequences of asymptomatic NCNGU are poorly investigated. Clinicians should be aware of the limitations of the evidence on which current screening guidelines for asymptomatic men are based.

PurposeThis research paper aims to examine the global trends in publishing in the leading marketing journals between 1964 and 2008, focusing on how public policy intervention in the assessment and funding of academic research has influenced Britain's relative productivity in the world's leading marketing journals.Design/methodology/approachThe method was an audit of contributions to the leading journals based on the authors' affiliation, country of origin and country in which they obtained their doctoral training.FindingsThe results show that the proportion of leading marketing publications by authors affiliated to British universities have held steady at about 2 per cent, while the productivity of several other countries has accelerated past Britain. However, to retain that share, Britain has increasingly depended upon importing people whose PhD is not British. This contrasts with some other European countries that are now more productive than Britain, but mainly recruit locals with local PhDs. The pattern of decline in the UK is related to the impact of Britain's research assessment exercise and the continuation of relatively weak social science research training.Research limitations/implicationsThe analysis is limited by only looking at one academic discipline and only the top few academic journals in the field.Practical implicationsThe findings have implications at several levels. At a national policy level it questions the value of the research assessment exercises that appear to have presided over a decline in research productivity. For institutions, it questions the value in investing in developing local talent when success has come to those who buy talent internationally. Perhaps, the major implication arises from Britain's academic productivity declining while neighbouring countries have grown in international excellence.Originality/valueAt a time when the continuation of expensive university research assessments is being questioned the research findings add value to the current debate in showing how that very process has accompanied academic decline.

In a paper in the last issue of Clinical Medicine, 1 some of the background to attitudes to newly dead bodies, the current context of an urgent need for organs for transplant and the objections to calling a proposal to address this 'presumed consent' were outlined. Here further concerns are explored.

We report low field DC SQUID NMR measurements down to 1.5 K of 3He adsorbed in the pores of the mesoporous molecular sieve MCM-41. In the first experiment measurements were made on 3He adsorbed onto the bare pore walls of MCM-41 with coverages ranging from $n_{^{3}\mathrm{He}}=0.86n_{1}$ to full pores at $n_{^{3}\mathrm{He}}=1.79n_{1}$ , where n 1 is the coverage for monolayer completion. A second experiment was performed with low 3He coverages ( $n_{^{3}\mathrm{He}}\sim0.01n_{1}$ ) on 4He preplated pores, where a crossover to a quasi-1D state is expected to occur at temperatures sufficiently below 700 mK. In both experiments relaxation times T 1 and T 2 * were measured as a function of temperature and coverage at frequencies from 80 to 240 kHz. The frequency dependence of the linewidth in the pure 3He experiment is extremely weak therefore T 2 * ≈T 2. The 1.5 K isotherm shows a small minimum in T 2 * at a coverage corresponding to monolayer completion. In the experiment with 4He preplating there was no significant change in T 1 or T 2 * when the 3He coverage was doubled from $n_{^{3}\mathrm{He}}=0.01n_{1}$ to 0.02n 1 at a 4He preplating of $n_{^{4}\mathrm{He}}=1.05n_{1}$ . This suggests that the relaxation times are dominated by single particle effects in the low density regime.

Measurements of the flow of thick 3He films over a highly polished silver surface, using a high precision torsional oscillator, have found unexpectedly long momentum relaxation times (Casey et al., Phys. Rev. Lett. 92, 255301, 2004). This results in a decoupling of the normal state helium film from the oscillator motion at low temperatures. In the ballistic regime the relaxation rate varies linearly with temperature. This result is explained by a theory in which the effect of surface roughness is incorporated into the transport equation as a disorder potential (Meyerovich and Stepaniants, J. Phys., Condens. Matter 12, 5575, 2000). This potential is fully characterised experimentally by AFM measurements of the surface roughness power spectrum, which we find to have a stretched exponential form. Incorporating the measured spectrum into the theory allows a direct comparison with the observed relaxation rate, with good agreement. The anomalous temperature dependence of the relaxation rate is accounted for by interference between bulk inelastic scattering and this weak surface elastic scattering. Decorating the substrate with scattering centres restores film-substrate coupling at the measurement frequency of 2.5 kHz. These results on the nature of quasiparticle scattering at rough surfaces may have implications in the understanding of the effects of confinement on superfluid 3He.

A 3He bilayer film adsorbed on graphite preplated with a bilayer of solid 4He has recently been shown to be a new heavy fermion system that can be tuned towards a quantum critical point (QCP) by varying the 3He coverage. We report new measurements of the temperature dependence of the magnetic susceptibility of this system over the temperature range 0.3 to 300 mK. The magnetisation of the 3He film is measured using pulsed NMR at a frequency of 60 kHz, on a SQUID detector setup with an untuned input circuit. The signal sensitivity attainable with this setup enables us to collect high-precision data with reasonable acquisition times, despite the low surface area of the sample (2 m2) and the small liquid susceptibility. The detailed NMR response provides an essential diagnostic tool to precisely adjust the 4He preplating. On cooling, the magnetisation evolves from Curie-law, through a distinct Kondo-like maximum at a temperature T*, to a weakly rising magnetisation far below the Curie law. This behaviour signifies the formation of the heavy fermion state of the coupled 3He layers. As the 3He coverage is increased towards the putative QCP, T* is tuned to lower temperature. These preliminary observations demonstrate the power of the technique, confirm previous results obtained in a different sample cell by a different method, and pave the way for a detailed study close to the QCP.

We present the preliminary results of our studies of superfluid 3He in a 0.6 μm thick slab using NMR. Below Tc the A phase is observed, and at low pressures the region of stability of the A phase extends down to the lowest temperatures reached, as described elsewhere. At pressures above 3.2 bar another, so far unidentified phase is observed at low temperatures. In this article we focus on the behavior of this phase and the transition between this phase and the A phase, all studied at 5.5 bar. The NMR response at low temperatures exhibits two possible frequency shifts and the transition is hysteretic in temperature.

We present the first study of the phase diagram of a thick film of superfluid 3He confined within a nanofabricated slab geometry. This cryogenic microfluidic chamber provides a well-defined environment for the superfluid, in which both the regular geometry and surface roughness may be fully characterised. The chamber is designed with a slab thickness d=0.6 μm and 3 mm thick walls to allow pressure tuning of the effective confinement between 0 and 5.5 bar. Over this range the zero temperature superfluid coherence length, ξ0, decreases by approximately a factor of two from 77 to 40 nm. Samples have so far been cooled to 350 μK. We use nuclear magnetic resonance (NMR) to ‘finger-print’ the superfluid order parameter, with the static field applied perpendicular to the slab. To enable us to resolve high quality NMR signals from the tiny amount of superfluid 3He in the slab, we have developed a spectrometer using a two stage SQUID amplifier with unprecedented sensitivity. Simple NMR zeugmatography allows the slab signal to be unambiguously distinguished from that of a small bulk liquid region near the fill line. The measured slab transition temperature, Tcslab, shows a suppression proportional to ξ02, as expected theoretically, but the absolute suppression is less than expected. Below Tcslab, an A-like phase is stable over a significant temperature range. A transition temperature, TAX, is measured on warming from a so far unidentified phase, occurring at lower temperatures, into the A-phase. At the pressures investigated (3 to 5.5 bar) the transition appears to occur at an approximately fixed value of the effective confinement d/ξ(TAX). In this geometry we predict that the A-phase will be stable to T=0 at zero pressure.

Brand extensions are increasingly used by multinational corporations in emerging markets such as China. However, understanding how consumers in the emerging markets evaluate brand extensions is hampered by a lack of research in the emerging markets contexts. To address the knowledge void, we built on an established brand extension evaluation framework in the West, namely Aaker and Keller (1990)1. Aaker , D. A. and Keller , K. L. 1990 . Consumer evaluations of brand extensions . Journal of Marketing , 54 ( 1 ) : 27 – 41 . [CrossRef], [Web of Science ®] View all references, and extended the model by incorporating two new factors: perceived fit based on brand image consistency and competition intensity in the brand extension category. The additions of two factors are made in recognition of the uniqueness of the considerations of consumers in the emerging markets in their brand extension evaluations. The extended model was tested by an empirical experiment using consumers in China. The results partly validated the Aaker and Keller model, and evidence that both newly added factors were significant in influencing consumers' evaluation of brand extensions was also found. More important, one new factor proposed, namely, consumer-perceived fit based on brand image consistency, was found to be more significant than all the factors in Aaker and Keller's original model, suggesting that the Aaker and Keller model may be limited in explaining how consumers in the emerging markets evaluate brand extensions. Further research implications and limitations are discussed in the paper.

In this report, the strategy and outcome of expanding SAR exploration to improve solubility and metabolic stability are discussed. Compound 35 exhibited excellent potency, selectivity over A(1) and improved solubility of >4 mg/mL at pH 8.0. In addition, compound 35 had good metabolic stability with a scaled intrinsic clearance of 3 mL/min/kg (HLM) and demonstrated efficacy in the haloperidol induced catalepsy model.

A novel series of potent zwitterionic uracil GnRH antagonists were discovered that showed reduced liability for CYP3A4 enzyme inhibition.

Incorporation of a carboxylic acid into a series of uracil derivatives as hGnRH-R antagonists resulted in a significant reduction of CYP3A4 inhibitory activity. Highly potent hGnRH antagonists with low CYP3A4 inhibitory liability, such as 8a and 8d, were identified. Thus, 8a had a K(i) of 2.2 nM at GnRH-R and an IC(50) of 36 microM at CYP3A4.

A series of N-pyrimidinyl-2-phenoxyacetamide adenosine A(2A) antagonists is described. SAR studies led to compound 14 with excellent potency (K(i) = 0.4 nM), selectivity (A(1)/A(2A) > 100), and efficacy (MED 10 mg/kg p.o.) in the rat haloperidol-induced catalepsy model for Parkinson's disease.

Some health-care institutions have ethics committees. The experience of the Ethical Issues Committee at the Royal College of Physicians is described. Ethics committees in institutions may be reactive or creative, must determine an agenda and must deal with dissent.

SAR studies were conducted around lead compound 1 using high-throughput parallel solution and solid phase synthesis. Our lead optimization efforts led to the identification of several CCR2b antagonists with potent activity in both binding and functional assays [Compound 71 CCR2b Binding IC 50 3.2 nM; MCP-1-Induced Chemotaxis IC 50 0.83 nM; Ca 2+ Flux IC 50 7.5 nM].

A series of trans-4-phenylpyrrolidine-3-carboxamides were synthesized and characterized as potent ligands of the human melanocortin-4 receptor. Interestingly, a pair of diastereoisomers 13b displayed potent functional agonist and antagonist activity, respectively. Thus, the 3S,4R-pyrrolidine 13b-1 possessed a Ki of 1.0 nM and an EC50 of 3.8 nM, while its 3R,4S-isomer 13b-2 exhibited a Ki of 4.7 and an IC50 of 64 nM. Both compounds were highly selective over other melanocortin receptor subtypes. The MC4R agonist 13b-1 also demonstrated efficacy in a diet-induced obesity model in rats.

Benzylamine and pyridinemethylamine derivatives were synthesized and characterized as potent and selective antagonists of the melanocortin-4 receptor (MC4R). These compounds were also profiled in rodents for their pharmacokinetic properties. Two compounds with diversified profiles in chemical structure, pharmacological activities, and pharmacokinetics, 10 and 12b, showed efficacy in an established murine cachexia model. For example, 12b had a K(i) value of 3.4 nM at MC4R, was more than 200-fold selective over MC3R, and had a good pharmacokinetic profile in mice, including high brain penetration. Moreover, 12b was able to stimulate food intake in the tumor-bearing mice and reverse their lean body mass loss. Our results provided further evidence that a potent and selective MC4R antagonist with appropriate pharmacokinetic properties might potentially be useful for the treatment of cancer cachexia.

A potent and selective antagonist of the melanocortin-4 receptor, 1-[2-[(1S)-(3-dimethylaminopropionyl)amino-2-methylpropyl]-6-methylphenyl]-4-[(2R)-methyl-3-(4-chlorophenyl)propionyl]piperazine (10d), was identified from a series piperazinebenzylamine attached with a N,N-dimethyl-beta-alanine side chain. This compound possessed high water solubility and exhibited good metabolic profiles. In animals, 10d showed moderate to good oral bioavailability and promoted food intake in tumor-bearing mice after oral administration.