Abstract
High-pressure electrical resistivity measurements reveal that the mechanical deformation of ultra-hard WB
2
during compression induces superconductivity above 50 GPa with a maximum ...superconducting critical temperature,
T
c
of 17 K at 91 GPa. Upon further compression up to 187 GPa, the
T
c
gradually decreases. Theoretical calculations show that electron-phonon mediated superconductivity originates from the formation of metastable stacking faults and twin boundaries that exhibit a local structure resembling MgB
2
(hP3, space group 191, prototype AlB
2
). Synchrotron x-ray diffraction measurements up to 145 GPa show that the ambient pressure hP12 structure (space group 194, prototype WB
2
) continues to persist to this pressure, consistent with the formation of the planar defects above 50 GPa. The abrupt appearance of superconductivity under pressure does not coincide with a structural transition but instead with the formation and percolation of mechanically-induced stacking faults and twin boundaries. The results identify an alternate route for designing superconducting materials.
Measurements at appropriate spatial and temporal scales are essential for understanding and monitoring spatially heterogeneous environments with complex and highly variable emission sources, such as ...in urban areas. However, the costs and complexity of conventional air quality measurement methods means that measurement networks are generally extremely sparse. In this paper we show that miniature, low-cost electrochemical gas sensors, traditionally used for sensing at parts-per-million (ppm) mixing ratios can, when suitably configured and operated, be used for parts-per-billion (ppb) level studies for gases relevant to urban air quality. Sensor nodes, in this case consisting of multiple individual electrochemical sensors, can be low-cost and highly portable, thus allowing the deployment of scalable high-density air quality sensor networks at fine spatial and temporal scales, and in both static and mobile configurations.
In this paper we provide evidence for the performance of electrochemical sensors at the parts-per-billion level, and then outline results obtained from deployments of networks of sensor nodes in both an autonomous, high-density, static network in the wider Cambridge (UK) area, and as mobile networks for quantification of personal exposure. Examples are presented of measurements obtained with both highly portable devices held by pedestrians and cyclists, and static devices attached to street furniture. The widely varying mixing ratios reported by this study confirm that the urban environment cannot be fully characterised using sparse, static networks, and that measurement networks with higher resolution (both spatially and temporally) are required to quantify air quality at the scales which are present in the urban environment. We conclude that the instruments described here, and the low-cost/high-density measurement philosophy which underpins it, have the potential to provide a far more complete assessment of the high-granularity air quality structure generally observed in the urban environment, and could ultimately be used for quantification of human exposure as well as for monitoring and legislative purposes.
► Suitably configured electrochemical sensors can be used for air quality studies. ► Evidence of performance of electrochemical sensors at parts-per-billion levels. ► Sensors are sensitive, low noise, highly linear and generally highly selective. ► Measurement density (space and time) unachievable using current methods. ► Show low-cost air quality sensor networks are now feasible for widespread use.
We have studied a three-drug combination with cyclophosphamide, bortezomib and dexamethasone (CyBorD) on a 28-day cycle in the treatment of newly diagnosed multiple myeloma (MM) patients to assess ...response and toxicity. The primary endpoint of response was evaluated after four cycles. Thirty-three newly diagnosed, symptomatic patients with MM received bortezomib 1.3 mg/m(2) intravenously on days 1, 4, 8 and 11, cyclophosphamide 300 mg/m(2) orally on days 1, 8, 15 and 22 and dexamethasone 40 mg orally on days 1-4, 9-12 and 17-20 on a 28-day cycle for four cycles. Responses were rapid with a mean 80% decline in the sentinel monoclonal protein at the end of two cycles. The overall intent to treat response rate (>or= partial response) was 88%, with 61% of very good partial response or better (>or=VGPR) and 39% of complete/near complete response (CR/nCR). For the 28 patients who completed all four cycles of therapy, the CR/nCR rate was 46% and VGPR rate was 71%. All patients undergoing stem cell harvest had a successful collection. Twenty-three patients underwent stem cell transplantation (SCT) and are evaluable through day 100 with CR/nCR documented in 70% and >or=VGPR in 74%. In conclusion, CyBorD produces a rapid and profound response in patients with newly diagnosed MM with manageable toxicity.
To investigate whether antibiotic exposure during the first year of life is associated with increased childhood body mass index (BMI).
Secondary analysis from a multi-centre, multi-country, ...cross-sectional study (The International Study of Asthma and Allergies in Childhood Phase Three).
A total of 74 946 children from 31 centres in 18 countries contributed data on antibiotic use in the first 12 months of life and current BMI.
Parents/guardians of children aged 5-8 years completed questionnaires that included questions about their children's current height and weight, and whether in the child's first 12 months of life, they had received any antibiotics, paracetamol, were breastfed or the mother/female guardian smoked cigarettes, and whether the child had wheezed in the past 12 months. A general linear mixed model was used to determine the association of antibiotic exposure with BMI, adjusting for age, sex, centre, BMI measurement type (self-reported or measured), maternal smoking, breastfeeding, paracetamol use, gross national income and current wheeze.
There was a significant interaction between sex and early-life antibiotic exposure. Early-life antibiotic exposure was associated with increased childhood BMI in boys (+0.107 kg m(-2), P<0.0001), but not in girls (-0.008 kg m(-2), P=0.75) after controlling for age, centre and BMI measurement type. The association remained in boys (+0.104 kg m(-2), P<0.0007), after adjustment for maternal smoking, breastfeeding, paracetamol use and current wheeze. There was no interaction between age, maternal smoking, breastfeeding, paracetamol use, gross national income and current wheeze in the association between early antibiotic exposure and BMI.
Exposure to antibiotics during the first 12 months of life is associated with a small increase in BMI in boys aged 5-8 years in this large international cross-sectional survey. By inference this provides additional support for the importance of gut microbiota in modulating the risk of obesity, with a sex-specific effect.
Although an African origin of the modern human species is generally accepted, the evolutionary processes involved in the spedation, geographical spread, and eventual extinction of archaic humans ...outside of Africa are much debated. An additional complexity has been the recent evidence of limited interbreeding between modern humans and the Neandertals and Denisovans. Modern human migrations and interactions began during the buildup to the Last Glacial Maximum, starting about 100,000 years ago. By examining the history of other organisms through glacial cycles, valuable models for evolutionary biogeography can be formulated. According to one such model, the adoption of a new refugium by a subgroup of a species may lead to important evolutionary changes.
Aims. The shape of low-frequency radio continuum spectra of normal galaxies is not well understood, the key question being the role of physical processes such as thermal absorption in shaping them. ...In this work we take advantage of the LOFAR Multifrequency Snapshot Sky Survey (MSSS) to investigate such spectra for a large sample of nearby star-forming galaxies. Methods. Using the measured 150 MHz flux densities from the LOFAR MSSS survey and literature flux densities at various frequencies we have obtained integrated radio spectra for 106 galaxies characterised by different morphology and star formation rate. The spectra are explained through the use of a three-dimensional model of galaxy radio emission, and radiation transfer dependent on the galaxy viewing angle and absorption processes. Results. Our galaxies’ spectra are generally flatter at lower compared to higher frequencies: the median spectral index αlow measured between ≈50 MHz and 1.5 GHz is −0.57 ± 0.01 while the high-frequency one αhigh, calculated between 1.3 GHz and 5 GHz, is −0.77 ± 0.03. As there is no tendency for the highly inclined galaxies to have more flattened low-frequency spectra, we argue that the observed flattening is not due to thermal absorption, contradicting the suggestion of Israel & Mahoney (1990, ApJ, 352, 30). According to our modelled radio maps for M 51-like galaxies, the free-free absorption effects can be seen only below 30 MHz and in the global spectra just below 20 MHz, while in the spectra of starburst galaxies, like M 82, the flattening due to absorption is instead visible up to higher frequencies of about 150 MHz. Starbursts are however scarce in the local Universe, in accordance with the weak spectral curvature seen in the galaxies of our sample. Locally, within galactic disks, the absorption effects are distinctly visible in M 51-like galaxies as spectral flattening around 100–200 MHz in the face-on objects, and as turnovers in the edge-on ones, while in M 82-like galaxies there are strong turnovers at frequencies above 700 MHz, regardless of viewing angle. Conclusions. Our modelling of galaxy spectra suggests that the weak spectral flattening observed in the nearby galaxies studied here results principally from synchrotron spectral curvature due to cosmic ray energy losses and propagation effects. We predict much stronger effects of thermal absorption in more distant galaxies with high star formation rates. Some influence exerted by the Milky Way’s foreground on the spectra of all external galaxies is also expected at very low frequencies.
Patients with multiple myeloma progressing on current therapies have limited treatment options. Pomalidomide (CC4047), an immunomodulatory drug, has significant activity in relapsed myeloma and ...previous studies suggest activity in lenalidomide refractory disease. To better define its efficacy in this group, we treated a cohort of lenalidomide refractory patients. Pomalidomide was given orally (2 mg) daily, continuously in 28-day cycles along with dexamethasone (40 mg) given weekly. Responses were assessed by the International Myeloma Working Group Criteria. Thirty-four patients were enrolled. The best response was very good partial response in 3 (9%), partial response (PR) in 8 (23%), best responses (MR) in 5 (15%), stable disease in 12 (35%) and progressive disease in 6 (18%), for an overall response rate of 47%. Of the 14 patients that were considered high risk, 8 (57%) had responses including 4 PR and 4 MR. The median time to response was 2 months and response duration was 9.1 months, respectively. The median overall survival was 13.9 months. Toxicity was primarily hematologic, with grade 3 or 4 toxicity seen in 18 patients (53%) consisting of anemia (12%), thrombocytopenia (9%) and neutropenia (26%). The combination of pomalidomide and dexamethasone (Pom/dex) is highly active and well tolerated in patients with lenalidomide-refractory myeloma.
Objective: Our objective was to evaluate the published literature and reach a consensus on the treatment of patients with ACTH-dependent Cushing’s syndrome, because there is no recent consensus on ...the management of this rare disorder.
Participants: Thirty-two leading endocrinologists, clinicians, and neurosurgeons with specific expertise in the management of ACTH-dependent Cushing’s syndrome representing nine countries were chosen to address 1) criteria for cure and remission of this disorder, 2) surgical treatment of Cushing’s disease, 3) therapeutic options in the event of persistent disease after transsphenoidal surgery, 4) medical therapy of Cushing’s disease, and 5) management of ectopic ACTH syndrome, Nelson’s syndrome, and special patient populations.
Evidence: Participants presented published scientific data, which formed the basis of the recommendations. Opinion shared by a majority of experts was used where strong evidence was lacking.
Consensus Process: Participants met for 2 d, during which there were four chaired sessions of presentations, followed by general discussion where a consensus was reached. The consensus statement was prepared by a steering committee and was then reviewed by all authors, with suggestions incorporated if agreed upon by the majority.
Conclusions: ACTH-dependent Cushing’s syndrome is a heterogeneous disorder requiring a multidisciplinary and individualized approach to patient management. Generally, the treatment of choice for ACTH-dependent Cushing’s syndrome is curative surgery with selective pituitary or ectopic corticotroph tumor resection. Second-line treatments include more radical surgery, radiation therapy (for Cushing’s disease), medical therapy, and bilateral adrenalectomy. Because of the significant morbidity of Cushing’s syndrome, early diagnosis and prompt therapy are warranted.
Despite its ubiquitous presence in the built environment, concrete's molecular-level properties are only recently being explored using experimental and simulation studies. Increasing societal ...concerns about concrete's environmental footprint have provided strong motivation to develop new concrete with greater specific stiffness or strength (for structures with less material). Herein, a combinatorial approach is described to optimize properties of cement hydrates. The method entails screening a computationally generated database of atomic structures of calcium-silicate-hydrate, the binding phase of concrete, against a set of three defect attributes: calcium-to-silicon ratio as compositional index and two correlation distances describing medium-range silicon-oxygen and calcium-oxygen environments. Although structural and mechanical properties correlate well with calcium-to-silicon ratio, the cross-correlation between all three defect attributes reveals an indentation modulus-to-hardness ratio extremum, analogous to identifying optimum network connectivity in glass rheology. We also comment on implications of the present findings for a novel route to optimize the nanoscale mechanical properties of cement hydrate.
This review of challenging diagnostic issues concerning high-grade endometrial carcinomas is derived from the authors' review of the literature followed by discussions at the Endometrial Cancer ...Workshop sponsored by the International Society of Gynecological Pathologists in 2016. Recommendations presented are evidence-based, insofar as this is possible, given that the levels of evidence are weak or moderate due to small sample sizes and nonuniform diagnostic criteria used in many studies. High-grade endometrioid carcinomas include FIGO grade 3 endometrioid carcinomas, serous carcinomas, clear cell carcinomas, undifferentiated carcinomas, and carcinosarcomas. FIGO grade 3 endometrioid carcinoma is diagnosed when an endometrioid carcinoma exhibits >50% solid architecture (excluding squamous areas), or when an architecturally FIGO grade 2 endometrioid carcinoma exhibits marked cytologic atypia, provided that a glandular variant of serous carcinoma has been excluded. The most useful immunohistochemical studies to make the distinction between these 2 histotypes are p53, p16, DNA mismatch repair proteins, PTEN, and ARID1A. Endometrial clear cell carcinomas must display prototypical architectural and cytologic features for diagnosis. Immunohistochemical stains, including, Napsin A and p504s can be used as ancillary diagnostic tools; p53 expression is aberrant in a minority of clear cell carcinomas. Of note, clear cells are found in all types of high-grade endometrial carcinomas, leading to a tendency to overdiagnose clear cell carcinoma. Undifferentiated carcinoma (which when associated with a component of low-grade endometrioid carcinoma is termed "dedifferentiated carcinoma") is composed of sheets of monotonous, typically dyscohesive cells, which can have a rhabdoid appearance; they often exhibit limited expression of cytokeratins and epithelial membrane antigen, are usually negative for PAX8 and hormone receptors, lack membranous e-cadherin and commonly demonstrate loss of expression of DNA mismatch repair proteins and SWI-SNF chromatin remodeling proteins. Carcinosarcomas must show unequivocal morphologic evidence of malignant epithelial and mesenchymal differentiation.
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