Reproductive factors and risk of oesophageal and gastric cancer in the Million Women Study cohort.

BACKGROUND: Hormonal factors may influence risk for upper gastrointestinal cancers in women. We examined risk of oesophageal and gastric cancers in relation to reproductive factors in a large UK cohort, the Million Women Study. METHODS: Among 1,319,409 women aged on average 56 years at recruitment, 1186 incident cancers of the oesophagus and 1194 of the stomach were registered during 11.9 million person-years' observation. Adjusted relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS: Risks of both oesophageal and gastric cancer were significantly higher in postmenopausal than in pre- or peri-menopausal women (RRs 1.46, 1.07-2.00 and 1.59, 1.15-2.20, respectively; P≤0.01 for both); and, among postmenopausal women, risk was higher the younger women were at menopause (RR, 95% CI per 5 years younger at menopause 1.18, 1.05-1.34 for oesophageal cancer and 1.18, 1.04-1.34 for stomach cancer, P(trend)=0.01 for both). For factors relating to childbearing, including women's age at first birth, their number of children, and breastfeeding history, the only significant association was a higher risk of oesophageal cancer in nulliparous, compared with parous, women (RR 1.31, 1.11-1.55; P=0.002). When risks for squamous cell and adenocarcinomas of the oesophagus were compared, most did not differ significantly, but statistical power was limited. CONCLUSION: Both oesophageal and gastric cancer risks appeared to be related to menopausal status and age at menopause, but there was little consistent evidence for associations with factors related to childbearing.

Neutron imaging of an operational dilution refrigerator.

The invention of the 3He/4He dilution refrigerator opened a new chapter in experimental ultra-low temperature physics. Dilution refrigerators became essential for providing ultra-low temperature environments for nuclear demagnetisation experiments, superconducting-qubit quantum processors and highly sensitive bolometers used in fundamental physics experiments. Development of dilution refrigeration technology requires thorough understanding of the quantum mechanical processes that take place in liquid helium at ultra-low temperatures. For decades the quantum fluids research community provided valuable information to engineers and designers involved in the development of advanced dilution refrigerators. However, the lack of methods that allow the measurement of physical parameters of liquid helium during the operation of a dilution refrigerator was hindering development of the technology. Here we show direct imaging of an operational dilution refrigerator using neutron radiography. This allows direct observation of the dilution process in 3He/4He mixtures and opens an opportunity for direct measurement of the 3He concentration. We observe the refrigerator behaviour in different regimes, such as continuous circulation and single shot, and show that our method allows investigation of various failure modes. Our results demonstrate that neutron imaging applied to the study of dilution refrigeration processes can provide essential information for developers of ultra-low temperature systems. We expect that neutron imaging will become instrumental in the research and development of advanced dilution refrigerators.

Phase II study of single agent capecitabine in the treatment of metastatic non-pancreatic neuroendocrine tumours.

BACKGROUND: This study sought to determine the safety of single agent capecitabine, a pro-drug of 5FU, in patients with metastatic non-pancreatic neuroendocrine tumours (NETs). METHODS: Multicentre phase II, first-line study design. Oral capecitabine was administered on days 1-14 of 3-week cycles. RESULTS: Treatment was safe and well tolerated. Common toxicities were diarrhoea and fatigue. CONCLUSION: The study provides evidence to support the use of capecitabine as a substitute for infusional 5FU in the management of NETs.

Continuous low-dose cyclophosphamide and methotrexate combined with celecoxib for patients with advanced cancer.

BACKGROUND: Combined therapy of metronomic cyclophosphamide, methotrexate and high-dose celecoxib targeting angiogenesis was used in a phase II trial. METHODS: Patients with advanced cancer received oral cyclophosphamide 50 mg o.d., celecoxib 400 mg b.d. and methotrexate 2.5 mg b.d. for two consecutive days each week. Response was determined every 8 weeks; toxicity was evaluated according to CTC version 2.0. Plasma markers of inflammation, coagulation and angiogenesis were measured. RESULTS: Sixty-seven of 69 patients were evaluable for response. Twenty-three patients had stable disease (SD) after 8 weeks, but there were no objective responses to therapy. Median time to progression was 57 days. There was a low incidence of toxicities. Among plasma markers, levels of tissue factor were higher in the SD group of patients at baseline, and levels of both angiopoietin-1 and matrix metalloproteinase-9 increased in the progressive disease group only. There were no changes in other plasma markers. CONCLUSION: This metronomic approach has negligible activity in advanced cancer albeit with minimal toxicity. Analysis of plasma markers indicates minimal effects on endothelium in this trial. These data for this particular regimen do not support basic tenets of metronomic chemotherapy, such as the ability to overcome resistant tumours by targeting the endothelium.

On the crystal structures and phase transitions of hydrates in the binary dimethyl sulfoxide-water system.

Neutron powder diffraction data have been collected from a series of flash-frozen aqueous solutions of dimethyl sulfoxide (DMSO) with concentrations between 25 and 66.7 mol% DMSO. These reveal the existence of three stoichiometric hydrates, which crystallize on warming between 175 and 195 K. DMSO trihydrate crystallizes in the monoclinic space group P21/c, with unit-cell parameters at 195 K of a = 10.26619 (3), b = 7.01113 (2), c = 10.06897 (3) Å, ß = 101.5030 (2)° and V = 710.183 (3) Å3 (Z = 4). Two of the symmetry-inequivalent water molecules form a sheet of tiled four- and eight-sided rings; the DMSO molecules are sandwiched between these sheets and linked along the b axis by the third water molecule to generate water-DMSO-water tapes. Two different polymorphs of DMSO dihydrate have been identified. The α phase is monoclinic (space group P21/c), with unit-cell parameters at 175 K of a = 6.30304 (4), b = 9.05700 (5), c = 11.22013 (7) Å, ß = 105.9691 (4)° and V = 615.802 (4) Å3 (Z = 4). Its structure contains water-DMSO-water chains, but these are polymerized in such a manner as to form sheets of reniform eight-sided rings, with the methyl groups extending on either side of the sheet. On warming above 198 K, α-DMSO·2H2O undergoes a solid-state transformation to a mixture of DMSO·3H2O + anhydrous DMSO, and there is then a stable eutectic between these two phases at ∼203 K. The ß-phase of DMSO dihydrate has been observed in a rapidly frozen eutectic melt and in very DMSO-rich mixtures. It is observed to be unstable with respect to the α-phase; above ∼180 K, ß-DMSO·2H2O converts irreversibly to α-DMSO·2H2O. At 175 K, the lattice parameters of ß-DMSO·2H2O are a = 6.17448 (10), b = 11.61635 (16), c = 8.66530 (12) Å, ß = 101.663 (1)° and V = 608.684 (10) Å3 (Z = 4), hence this polymorph is just 1.16% denser than the α-phase under identical conditions. Like the other two hydrates, the space group appears likely, on the basis of systematic absences, to be P21/c, but the structure has not yet been determined. Our results reconcile 60 years of contradictory interpretations of the phase relations in the binary DMSO-water system, particularly between mole fractions of 0.25-0.50, and confirm empirical and theoretical studies of the liquid structure around the eutectic composition (33.33 mol% DMSO).

Sample environment for neutron scattering measurements of internal stresses in engineering materials in the temperature range of 6 K to 300 K.

Internal stresses in materials have a considerable effect on material properties including strength, fracture toughness, and fatigue resistance. The ENGIN-X beamline is an engineering science facility at ISIS optimized for the measurement of strain and stress using the atomic lattice planes as a strain gauge. Nowadays, the rapidly rising interest in the mechanical properties of engineering materials at low temperatures has been stimulated by the dynamic development of the cryogenic industry and the advanced applications of the superconductor technology. Here we present the design and discuss the test results of a new cryogenic sample environment system for neutron scattering measurements of internal stresses in engineering materials under a load of up to 100 kN and in the temperature range of 6 K to 300 K. Complete cooling of the system starting from the room temperature down to the base temperature takes around 90 min. Understanding of internal stresses in engineering materials at cryogenic temperatures is vital for the modelling and designing of cutting-edge superconducting magnets and other superconductor based applications.

Segregated water observed in a putative fish embryo cryopreservative.

Development of new cryopreservation strategies has major potential in medicine and agriculture and is critical to the conservation of endangered species that currently cannot be preserved. A critical property of any potential cryopreservative solution is its ability to prevent cell-damaging ice formation during cooling and subsequent heating. This study focuses on the freezing behaviour of promising model cryoprotective solutions. We perform neutron scattering analysis, combined with computer modelling, of the water structure after quench cooling these solutions. It is found that water in this solution forms nano-clusters encapsulated by the surrounding matrix of cryoprotectant solute molecules. We posit that these small volumes inhibit ice formation, because water does not have space for the structural relaxation required to crystallize on the timescale of the cooling process.

A high temperature cell for simultaneous electrical resistance and neutron diffraction measurements.

An in situ cell that allows the electrical resistance of a sample pellet to be measured while performing neutron diffraction experiments has been developed at the ISIS pulsed neutron source. The sample is held between two spring loaded platinum electrodes embedded in a boron nitride clamp assembly with the resistance measured using the four-probe method. An outer quartz glass jacket allows the atmosphere within the sample enclosure to be controlled, and the entire device can be accommodated within a standard ISIS neutron furnace for measurements at temperatures up to 1270 K. The operation of this cell is illustrated using data for the structural, magnetic, and electrical properties of chalcopyrite CuFeS(2) collected over the temperature range of 398-873 K on the Polaris powder diffractometer at ISIS.

Bose-Einstein condensation in solid 4He.

We present neutron scattering measurements of the atomic momentum distribution n(k) in solid helium under a pressure p=41 bar (molar volume Vm=20.01+/-0.02 cm3/mol) and at temperatures between 80 and 500 mK. The aim is to determine whether there is Bose-Einstein condensation (BEC) below the critical temperature, Tc=200 mK, where a superfluid density has been observed. Assuming BEC appears as a macroscopic occupation of the k=0 state below Tc, we find a condensate fraction of n0=(-0.10+/-1.20)% at T=80 mK and n0=(0.08+/-0.78)% at T=120 mK, consistent with zero. The shape of n(k) also does not change on crossing Tc within measurement precision.

Measurement of the kinetic energy and lattice constant in hcp solid helium at temperatures 0.07-0.4 K.

The single atom kinetic energy kappa of high purity solid hcp 4He has been measured by neutron Compton scattering, at temperatures between 0.07 and 0.4 K and a pressure of 40 bar. Within statistical error of approximately 2% no change in kappa was observed. The values of kappa at approximately 0.07 K were the same in a single crystal and a polycrystalline sample and were also unaffected (within statistical error) by the addition of 10 ppm of 3He. The lattice constant was also found to be independent of temperature to within 1 part in 2000. These results suggest that the supersolid transition in 4He has a different microscopic origin to the superfluid transition in the liquid.

Surface fluctuations of normal and superfluid 3He probed by Wigner solid dynamics.

Electron scattering from surface fluctuations on normal and superfluid 3He has been measured by its effect on the linewidth of the low-wave-vector transverse magnetophonon mode of the electron crystal (the Wigner solid) floating on the helium surface. The relaxation rate becomes anomalously low below 70 mK, and reaches a plateau at about 3 times less than its expected value before dropping further at the superfluid transition. The absence of such anomalous behavior on 4He suggests that the effect is specific to liquid 3He.