The selective recruitment of regulatory t cells to human colorectal cancer

Regulatory T cells (Treg) are enriched in tumour tissue relative to other compartments. Anti-tumour immunity is promoted through their depletion. It is hypothesised that Treg are recruited to human colorectal cancer (CRC) via a specific combination of chemokine receptors and integrins, blockade of which reduces tumour Treg recruitment, ameliorating the anti-tumour immune response. A systematic examination was conducted of receptors expressed by CRC-isolated Treg and the cognate ligands expressed by CRC. The effects of receptor inhibition were tested in murine models of colorectal cancer. Human CRC-infiltrating Treg exhibit a specific chemokine receptor signature, expressing significantly higher levels of CCR5 than conventional T cells. CRC expresses the ligands for CCR5 at significantly higher levels than distal tissue. Isolated Treg migrated towards CCR5 ligands in vitro and suppressed allogeneic T cell proliferation. CCR5 inhibition in murine models of CRC led to delayed tumour growth but had no effect on tumour Treg infiltration compared with vehicle control. CCR5 inhibition is unlikely to provide any significant reduction in the infiltration of Treg into human CRC. Given the effects CCR5 inhibition had on tumour growth, CCR5 antagonists command further investigation into their potential role as novel therapeutic agents in the treatment armoury against human CRC

First-order melting of a weak spin-orbit Mott insulator into a correlated metal

The electronic phase diagram of the weak spin-orbit Mott insulator (Sr(1-x)Lax)3Ir2O7 is determined via an exhaustive experimental study. Upon doping electrons via La substitution, an immediate collapse in resistivity occurs along with a narrow regime of nanoscale phase separation comprised of antiferromagnetic, insulating regions and paramagnetic, metallic puddles persisting until x~0.04. Continued electron doping results in an abrupt, first-order phase boundary where the Neel state is suppressed and a homogenous, correlated, metallic state appears with an enhanced spin susceptibility and local moments. As the metallic state is stabilized, a weak structural distortion develops and suggests a competing instability with the parent spin-orbit Mott state.Comment: 5 pages, 4 figure

Sound Coiled-Tubing Drilling Practices

This Coiled-Tubing Drilling (CTD) Sound Practices Manual provides tools needed by CTD engineers and supervisors to plan, design and perform safe, successful CTD operations. As emphasized throughout, both careful planning and attention to detail are mandatory for success. A bibliography of many useful CTD references is presented in Chapter 6. This manual is organized according to three processes: 1) Pre-Job Planning Process, 2) Operations Execution Process, and 3) Post-Job Review Process. Each is discussed in a logical and sequential format

Anisotropy of thermal conductivity oscillations in relation to the Kitaev spin liquid phase

In the presence of external magnetic field, the Kitaev model could either hosts gapped topological anyon or gapless Majorana fermions. In $\alpha$-RuCl$_3$, the gapped and gapless cases are only separated by a thirty-degree rotation of the in-plane magnetic field vector. The presence/absence of the spectral gap is key for understanding the thermal transport behavior in $\alpha$-RuCl$_3$. Here, we study the anisotropy of the oscillatory features of thermal conductivity in $\alpha$-RuCl$_3$. We examine the oscillatory features of thermal conductivities (k//a, k//b) with fixed external fields and found distinct behavior for the gapped (B//a) and gapless (B//b) scenarios. Furthermore, we track the evolution of thermal resistivity ($\lambda_{a}$) and its oscillatory features with the rotation of in-plane magnetic fields from B//b to B//a. The thermal resistivity $\lambda (B,\theta)$ display distinct rotational symmetries before and after the emergence of the field induced Kitaev spin liquid phase. These experiment data suggest close correlations between the oscillatory features of thermal conductivity, the underlying Kitaev spin liquid phase and the fermionic excitation it holds

Conversion of colonoscopy to flexible sigmoidoscopy: an unintended consequence of quality measurement in endoscopy

OBJECTIVE: To quantify the proportion of requests for colonoscopy that are performed as flexible sigmoidoscopy and documented reasons for this in ordinary UK hospital practice. To determine the effect these requests have on colonoscopy completion rate if they are included in the denominator of the calculated rate by individual endoscopist. DESIGN: Retrospective study of 22 months flexible sigmoidoscopy practice at a major UK teaching hospital. All flexible sigmoidoscopies performed had their associated request form examined. SETTING: UK NHS University Hospital. PATIENTS: All patients receiving outpatient flexible sigmoidoscopy from January 2013 to October 2014 with no exclusions. INTERVENTION: Conversion of colonoscopy to flexible sigmoidoscopy. MAIN OUTCOME MEASURES: Conversion of colonoscopy to flexible sigmoidoscopy, reason for conversion and adjusted colonoscopy completion rate. RESULTS: 71 of the 3526 flexible sigmoidoscopies performed (2.0%), representing 71 of 5905 colonoscopy requests (1.2%). Conversion reason was noted only in 26 (37%) of converted cases. Adjustment of colonoscopy completion rate to include conversions pushed four of our unit's 22 endoscopists below the UK national 90% standard. CONCLUSIONS: Conversion to flexible sigmoidoscopy occurs in 1.2% of patients originally booked for colonoscopy. The reason for this conversion is often unqualified and may be inappropriate. Conversion can affect the colonoscopy completion rate, and therefore, should be included in endoscopists’ overall performance statistics

A new class of large-amplitude radial-mode hot subdwarf pulsators

Using high-cadence observations from the Zwicky Transient Facility at low Galactic latitudes, we have discovered a new class of pulsating, hot compact stars. We have found four candidates, exhibiting blue colors (g − r ≤ −0.1 mag), pulsation amplitudes of >5%, and pulsation periods of 200–475 s. Fourier transforms of the light curves show only one dominant frequency. Phase-resolved spectroscopy for three objects reveals significant radial velocity, T eff, and log(g) variations over the pulsation cycle, which are consistent with large-amplitude radial oscillations. The mean T eff and log(g) for these stars are consistent with hot subdwarf B (sdB) effective temperatures and surface gravities. We calculate evolutionary tracks using MESA and adiabatic pulsations using GYRE for low-mass, helium-core pre-white dwarfs (pre-WDs) and low-mass helium-burning stars. Comparison of low-order radial oscillation mode periods with the observed pulsation periods show better agreement with the pre-WD models. Therefore, we suggest that these new pulsators and blue large-amplitude pulsators (BLAPs) could be members of the same class of pulsators, composed of young ≈0.25–0.35 M ⊙ helium-core pre-WDs.Published versio