Remotely triggered scaffolds for controlled release of pharmaceuticals

Fe3O4-Au hybrid nanoparticles (HNPs) have shown increasing potential for biomedical applications such as image guided stimuli responsive drug delivery. Incorporation of the unique properties of HNPs into thermally responsive scaffolds holds great potential for future biomedical applications. Here we successfully fabricated smart scaffolds based on thermo-responsive poly(N-isopropylacrylamide) (pNiPAM). Nanoparticles providing localized trigger of heating when irradiated with a short laser burst were found to give rise to remote control of bulk polymer shrinkage. Gold-coated iron oxide nanoparticles were synthesized using wet chemical precipitation methods followed by electrochemical coating. After subsequent functionalization of particles with allyl methyl sulfide, mercaptodecane, cysteamine and poly(ethylene glycol) thiol to enhance stability, detailed biological safety was determined using live/dead staining and cell membrane integrity studies through lactate dehydrogenase (LDH) quantification. The PEG coated HNPs did not show significant cytotoxic effect or adverse cellular response on exposure to 7F2 cells (p < 0.05) and were carried forward for scaffold incorporation. The pNiPAM-HNP composite scaffolds were investigated for their potential as thermally triggered systems using a Q-switched Nd:YAG laser. These studies show that incorporation of HNPs resulted in scaffold deformation after very short irradiation times (seconds) due to internal structural heating. Our data highlights the potential of these hybrid-scaffold constructs for exploitation in drug delivery, using methylene blue as a model drug being released during remote structural change of the scaffold

On the importance of testing gravity at distances less than 1cm

If the mechanism responsible for the smallness of the vacuum energy is consistent with local quantum field theory, general arguments suggest the existence of at least one unobserved scalar particle with Compton wavelength bounded from below by one tenth of a millimeter. We show that this bound is saturated if vacuum energy is a substantial component of the energy density of the universe. Therefore, the success of cosmological models with a significant vacuum energy component suggests the existence of new macroscopic forces with range in the sub-millimeter region. There are virtually no experimental constraints on the existence of quanta with this range of interaction.Comment: 9 pages TeX, 2 eps figures, uses mtexsis.tex and epsf.tex. Entry in 1996 Gravity Research Foundation essay competition. To be published in the Journal of General Relativity and Gravitatio

Carboplatin/taxane-induced gastrointestinal toxicity: a pharmacogenomics study on the SCOTROC1 trial

Carboplatin/taxane combination is first-line therapy for ovarian cancer. However, patients can encounter treatment delays, impaired quality of life, even death because of chemotherapy-induced gastrointestinal (GI) toxicity. A candidate gene study was conducted to assess potential association of genetic variants with GI toxicity in 808 patients who received carboplatin/taxane in the Scottish Randomized Trial in Ovarian Cancer 1 (SCOTROC1). Patients were randomized into discovery and validation cohorts consisting of 404 patients each. Clinical covariates and genetic variants associated with grade III/IV GI toxicity in discovery cohort were evaluated in replication cohort. Chemotherapy-induced GI toxicity was significantly associated with seven single-nucleotide polymorphisms in the ATP7B, GSR, VEGFA and SCN10A genes. Patients with risk genotypes were at 1.53 to 18.01 higher odds to develop carboplatin/taxane-induced GI toxicity (P&#60;0.01). Variants in the VEGF gene were marginally associated with survival time. Our data provide potential targets for modulation/inhibition of GI toxicity in ovarian cancer patients

A Search for Scalar Chameleons with ADMX

Scalar fields with a "chameleon" property, in which the effective particle mass is a function of its local environment, are common to many theories beyond the standard model and could be responsible for dark energy. If these fields couple weakly to the photon, they could be detectable through the "afterglow" effect of photon-chameleon-photon transitions. The ADMX experiment was used in the first chameleon search with a microwave cavity to set a new limit on scalar chameleon-photon coupling excluding values between 2*10^9 and 5*10^14 for effective chameleon masses between 1.9510 and 1.9525 micro-eV.Comment: 4 pages, 3 figure

Boundary-layer friction in midlatitude cyclone

Results from an idealized three-dimensional baroclinic life-cycle model are interpreted in a potential vorticity (PV) framework to identify the physical mechanisms by which frictional processes acting in the atmospheric boundary layer modify and reduce the baroclinic development of a midlatitude storm. Considering a life cycle where the only non-conservative process acting is boundary-layer friction, the rate of change of depth-averaged PV within the boundary layer is governed by frictional generation of PV and the flux of PV into the free troposphere. Frictional generation of PV has two contributions: Ekman generation, which is directly analogous to the well-known Ekman-pumping mechanism for barotropic vortices, and baroclinic generation, which depends on the turning of the wind in the boundary layer and low-level horizontal temperature gradients. It is usually assumed, at least implicitly, that an Ekman process of negative PV generation is the mechanism whereby friction reduces the strength and growth rates of baroclinic systems. Although there is evidence for this mechanism, it is shown that baroclinic generation of PV dominates, producing positive PV anomalies downstream of the low centre, close to developing warm and cold fronts. These PV anomalies are advected by the large-scale warm conveyor belt flow upwards and polewards, fluxed into the troposphere near the warm front, and then advected westwards relative to the system. The result is a thin band of positive PV in the lower troposphere above the surface low centre. This PV is shown to be associated with a positive static stability anomaly, which Rossby edge wave theory suggests reduces the strength of the coupling between the upper- and lower-level PV anomalies, thereby reducing the rate of baroclinic development. This mechanism, which is a result of the baroclinic dynamics in the frontal regions, is in marked contrast with simple barotropic spin-down ideas. Finally we note the implications of these frictionally generated PV anomalies for cyclone forecasting

A SQUID-based microwave cavity search for dark-matter axions

Axions in the micro eV mass range are a plausible cold dark matter candidate and may be detected by their conversion into microwave photons in a resonant cavity immersed in a static magnetic field. The first result from such an axion search using a superconducting first-stage amplifier (SQUID) is reported. The SQUID amplifier, replacing a conventional GaAs field-effect transistor amplifier, successfully reached axion-photon coupling sensitivity in the band set by present axion models and sets the stage for a definitive axion search utilizing near quantum-limited SQUID amplifiers.Comment: 4 pages, 5 figures, submitted to PR

The effect of a sports chiropractic manual therapy intervention on the prevention of back pain, hamstring and lower limb injuries in semi-elite Australian Rules footballers: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Hamstring injuries are the most common injury in Australian Rules football. It was the aims to investigate whether a sports chiropractic manual therapy intervention protocol provided in addition to the current best practice management could prevent the occurrence of and weeks missed due to hamstring and other lower-limb injuries at the semi-elite level of Australian football.</p> <p>Methods</p> <p>Sixty male subjects were assessed for eligibility with 59 meeting entry requirements and randomly allocated to an intervention (n = 29) or control group (n = 30), being matched for age and hamstring injury history. Twenty-eight intervention and 29 control group participants completed the trial. Both groups received the current best practice medical and sports science management, which acted as the control. Additionally, the intervention group received a sports chiropractic intervention. Treatment for the intervention group was individually determined and could involve manipulation/mobilization and/or soft tissue therapies to the spine and extremity. Minimum scheduling was: 1 treatment per week for 6 weeks, 1 treatment per fortnight for 3 months, 1 treatment per month for the remainder of the season (3 months). The main outcome measure was an injury surveillance with a missed match injury definition.</p> <p>Results</p> <p>After 24 matches there was no statistical significant difference between the groups for the incidence of hamstring injury (OR:0.116, 95% CI:0.013-1.019, p = 0.051) and primary non-contact knee injury (OR:0.116, 95% CI:0.013-1.019, p = 0.051). The difference for primary lower-limb muscle strains was significant (OR:0.097, 95%CI:0.011-0.839, p = 0.025). There was no significant difference for weeks missed due to hamstring injury (4 v14, χ2:1.12, p = 0.29) and lower-limb muscle strains (4 v 21, χ2:2.66, p = 0.10). A significant difference in weeks missed due to non-contact knee injury was noted (1 v 24, χ2:6.70, p = 0.01).</p> <p>Conclusions</p> <p>This study demonstrated a trend towards lower limb injury prevention with a significant reduction in primary lower limb muscle strains and weeks missed due to non-contact knee injuries through the addition of a sports chiropractic intervention to the current best practice management.</p> <p>Trial registration</p> <p>The study was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12608000533392).</p

The relationship between aortic wall distensibility and rupture of infrarenal abdominal aortic aneurysm

AbstractObjective: A more accurate means of prediction of abdominal aortic aneurysm (AAA) rupture would improve the clinical and cost effectiveness of prophylactic repair. The purpose of this study was to determine whether AAA wall distensibility can be used to predict time to rupture independently of other recognized risk factors. Methods: A prospective, six-center study of 210 patients with AAA in whom blood pressure (BP), maximum AAA diameter (Dmax), and AAA distensibility (pressure strain elastic modulus [Ep] and stiffness [β]) were measured at 6 months with an ultrasound scan-based echo-tracking technique. A stepwise, time-dependent, Cox proportional hazards model was used to determine the effect on time to rupture of age, gender, BP, Dmax, BP, Ep, β, and change in Dmax, Ep, and β adjusted for time between follow-up visits. Results: Median (interquartile range) AAA diameter was 48 mm (41 to 54 mm), median age was 72 years (68 to 77 years), and median follow-up period was 19 months (9 to 30 months). In the Cox model, female gender (hazards ratio [HR], 2.78; 95% CI, 1.23 to 6.28; P =.014), larger Dmax (HR, 1.36 for 10% increase in Dmax; 95% CI, 1.12 to 1.66; P =.002), higher diastolic BP (HR, 1.13 for 10% increase in BP; 95% CI, 1.13 to 1.92; P =.004), and a decrease in Ep (increase in distensibility) over time (HR, 1.38 for 10% decrease in Ep over 6 months; 95% CI, 1.08 to 1.78; P =.010) significantly reduced the time to rupture (had a shorter time to rupture). Conclusion: Women have a shorter time to AAA rupture. The measurement of AAA distensibility, diastolic BP, and diameter may provide a more accurate assessment of rupture risk than diameter alone. (J Vasc Surg 2003;37:112-7.

Impact of Gulf Stream SST biases on the global atmospheric circulation

The UK Met Office Unified Model in the Global Coupled 2 (GC2) configuration has a warm bias of up to almost 7K in the Gulf Stream SSTs in the winter season, which is associated with surface heat flux biases and potentially related to biases in the atmospheric circulation. The role of this SST bias is examined with a focus on the tropospheric response by performing three sensitivity experiments. The SST biases are imposed on the atmosphere-only configuration of the model over a small and medium section of the Gulf Stream, and also the wider North Atlantic. Here we show that the dynamical response to this anomalous Gulf Stream heating (and associated shifting and changing SST gradients) is to enhance vertical motion in the transient eddies over the Gulf Stream, rather than balance the heating with a linear dynamical meridional wind or meridional eddy heat transport. Together with the imposed Gulf Stream heating bias, the response affects the troposphere not only locally but also in remote regions of the Northern Hemisphere via a planetary Rossby wave response. The sensitivity experiments partially reproduce some of the differences in the coupled configuration of the model relative to the atmosphere-only configuration and to the ERA-Interim reanalysis. These biases may have implications for the ability of the model to respond correctly to variability or changes in the Gulf Stream. Better global prediction therefore requires particular focus on reducing any large western boundary current SST biases in these regions of high ocean-atmosphere interaction