Wetting of real engineering surfaces occurs in many industrial applications (liquid coating, lubrication, printing, painting, …). Forced and natural wetting can be beneficial in many cases, providing ...lubrication and therefore reducing friction and wear. However the wettability of surfaces can be strongly affected by surface roughness. This influence can be very significant for static and dynamic wetting
1. In this paper authors experimentally investigate the roughness influence on contact angle measurements and propose a simple model combining Wenzel and Cassie–Baxter theories with simple 2D roughness profile analysis. The modelling approach is applied to real homogeneous anisotropic surfaces, manufactured on a wide range of engineering materials including aluminium alloy, iron alloy, copper, ceramic, plastic (poly-methylmethacrylate: PMMA) and titanium alloy.
Empirically supported psychological treatments have been developed for a range of psychiatric disorders but there is evidence that patients are not receiving them in routine clinical care. ...Furthermore, even when patients do receive these treatments there is evidence that they are often not well delivered. The aim of this paper is to identify the barriers to the dissemination of evidence-based psychological treatments and then propose ways of overcoming them, hence potentially bridging the gap between research findings and clinical practice.
Calprotectin is a granulocyte neutrophil-predominant cytosolic protein. Fecal concentrations are elevated in intestinal inflammation and may predict relapse in quiescent inflammatory bowel disease. ...We aim to investigate fecal calprotectin (FC) as a biomarker in predicting the clinical course of acute severe ulcerative colitis (ASUC).
In 90 patients with ASUC requiring intensive in-patient medical therapy (January 2005-September 2007), we investigated the discriminant ability of FC to predict colectomy and corticosteroid and infliximab nonresponse. All patients received parenteral corticosteroids as first-line treatment; 21 (23.3%) were also treated with infliximab (5 mg/kg), after failure of corticosteroid therapy.
Of 90 patients, 31 (34.4%) required colectomy, including 11 (52.4%) of those treated with infliximab. Overall FC was high (1,020.0 microg/g interquartile range: 601.5-1,617.5). FC was significantly higher in patients requiring colectomy (1,200.0 vs. 887.0; P=0.04), with a trend toward significance when comparing corticosteroid nonresponders and responders (1,100.0 vs. 863.5; P=0.08), as well as between infliximab nonresponders and responders (1,795.0 vs. 920.5; P=0.06). Receiver-operator characteristic curve analysis yielded an area under the curve of 0.65 to predict colectomy (P=0.04), with a maximum likelihood ratio of 9.23, specificity 97.4%, and sensitivity 24.0% at a cutoff point of 1,922.5 microg/g. Kaplan-Meier analyses showed that using 1,922.5 microg/g over a median follow-up of 1.10 years, 87% of patients will need subsequent colectomy.
This is the first data set to demonstrate that FC levels are dramatically elevated in severe UC. These data raise the possibility that this biomarker can predict response to first or second-line medical therapy in this setting.
ABSTRACT White dwarf stars frequently experience external pollution by heavy elements, and yet the intrinsically carbon-enriched DQ spectral class members fail to exhibit this phenomenon, ...representing a decades-old conundrum. This study reports a high-resolution spectroscopic search for Ca ii in classical DQ white dwarfs, finding that these stars are stunted both in pollution frequency and heavy element mass fractions, relative to the wider population. Compared to other white dwarf spectral classes, the average external accretion rate is found to be at least three orders of magnitude lower in the DQ stars. Several hypotheses are considered which need to simultaneously account for (i) an apparent lack of accreted metals, (ii) a dearth of circumstellar planetary material, (iii) an observed deficit of unevolved companions in post-common envelope binaries, (iv) relatively low helium mass fractions, and remnant masses that appear smaller than for other spectral classes, (v) a high incidence of strong magnetism, and (vi) modestly older disc kinematics. Only one hypothesis is consistent with all these constraints, suggesting DQ white dwarfs are the progeny of binary evolution that altered both their stellar structures and their circumstellar environments. A binary origin is already suspected for the warmer and more massive DQ stars, and is proposed here as an inclusive mechanism to expose core carbon material, in a potential evolutionary unification for the entire DQ spectral class. In this picture, DQ stars are not descended from DA or DB white dwarfs that commonly host dynamically active planetary systems.
Pancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on ...analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours.
Aliment Pharmacol Ther 2011; 33: 946–953
Summary
Background Adalimumab is efficacious therapy for adults with Crohn’s disease (CD).
Aim To summarise the United Kingdom and Republic of Ireland ...paediatric adalimumab experience.
Methods British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) members with Inflammatory Bowel Disease (IBD) patients <18 years old commencing adalimumab with at least 4 weeks follow‐up. Patient demographics and details of treatment were then collected. Response and remission was assessed using the Paediatric Crohn’s Disease Activity Index (PCDAI)/Physicians Global Assessment (PGA).
Results Seventy‐two patients 70 CD, 1 ulcerative colitis (UC), 1 IBD unclassified (IBDU) from 19 paediatric‐centres received adalimumab at a median age of 14.8 (IQR 3.1, range 6.1–17.8) years; 66/70 CD (94%) had previously received infliximab. A dose of 80 mg then 40 mg was used for induction in 41(59%) and 40 mg fortnightly for maintenance in 61 (90%). Remission rates were 24%, 58% and 41% at 1, 6 and 12 months, respectively. Overall 43 (61%) went into remission at some point, with 24 (35%) requiring escalation of therapy. Remission rates were higher in those on concomitant immunosuppression cf. those not on immunosuppression 34/46 (74%) vs. 9/24 (37%), respectively, (χ28.8, P = 0.003). There were 15 adverse events (21%) including four (6%) serious adverse events with two sepsis related deaths in patients who were also on immunosuppression and home parenteral nutrition (3% mortality rate).
Conclusions Adalimumab is useful in treatment of refractory paediatric patients with a remission rate of 61%. This treatment benefit should be balanced against side effects, including in this study a 3% mortality rate.
ABSTRACT
This article reports quasi-continuous transiting events towards WD 1054–226 at d = 36.2 pc and V = 16.0 mag, based on simultaneous, high-cadence, multiwavelength imaging photometry using ...ULTRACAM over 18 nights from 2019 to 2020 March. The predominant period is 25.02 h and corresponds to a circular orbit with blackbody Teq = 323 K, where a planetary surface can nominally support liquid water. The light curves reveal remarkable night-to-night similarity, with changes on longer time-scales, and lack any transit-free segments of unocculted starlight. The most pronounced dimming components occur every 23.1 min – exactly the 65th harmonic of the fundamental period – with depths of up to several per cent, and no evident colour dependence. Myriad additional harmonics are present, as well as at least two transiting features with independent periods. High-resolution optical spectra are consistent with stable, photospheric absorption by multiple, refractory metal species, with no indication of circumstellar gas. Spitzer observations demonstrate a lack of detectable dust emission, suggesting that the otherwise hidden circumstellar disc orbiting WD 1054–226 may be typical of polluted white dwarfs, and detected only via favourable geometry. Future observations are required to constrain the orbital eccentricity, but even if periastron is near the Roche limit, sublimation cannot drive mass loss in refractory parent bodies, and collisional disintegration is necessary for dust production.
The human epidermal growth factor receptor (HER) family consists of four members: ErbB-1 (HER1), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4). These receptors activate numerous downstream pathways ...in response to extracellular ligands, regulating diverse processes that include differentiation, migration, proliferation, and survival. Alterations in these genes play a role in the development and progression of many human cancers. In gastric carcinomas (GCs), expression of HER1 and HER2 is thought to be a prognostic factor and target of novel biologic agents. The effect of HER3 or HER4 expression in GC has not been sufficiently studied. In this study, we explored the gene and protein expression of the HER family in GC to establish new potential prognostic factors.
Immunohistochemistry and fluorescence in situ hybridization were performed in 221 patients with GC using tissue microarray. Correlation between the expression or amplification of HER genes and the clinicopathologic parameters was statistically analyzed.
Alterations of members of the HER family were significantly associated with the parameters involved in tumor progression, including depth of tumor invasion, involved lymph nodes, and tumor stage. In addition, HER2 amplification and HER3 expression were significantly related to worse survival.
These results reveal that all members of the HER family are expressed in GC. Furthermore, expression of HER2 and HER3 is a significant predictor of poor survival in GC. Therefore, the development of HER-targeted agents and agents targeting downstream signaling pathways provides new possibilities in the treatment of GC.
ABSTRACT
Based on HARPS-N radial velocities (RVs) and TESS photometry, we present a full characterization of the planetary system orbiting the late G dwarf TOI-561. After the identification of three ...transiting candidates by TESS, we discovered two additional external planets from RV analysis. RVs cannot confirm the outer TESS transiting candidate, which would also make the system dynamically unstable. We demonstrate that the two transits initially associated with this candidate are instead due to single transits of the two planets discovered using RVs. The four planets orbiting TOI-561 include an ultra-short period (USP) super-Earth (TOI-561 b) with period Pb = 0.45 d, mass Mb = 1.59 ± 0.36 M⊕ and radius Rb = 1.42 ± 0.07 R⊕, and three mini-Neptunes: TOI-561 c, with Pc = 10.78 d, Mc = 5.40 ± 0.98 M⊕, Rc = 2.88 ± 0.09 R⊕; TOI-561 d, with Pd = 25.6 d, Md = 11.9 ± 1.3 M⊕, Rd = 2.53 ± 0.13 R⊕; and TOI-561 e, with Pe = 77.2 d, Me = 16.0 ± 2.3 M⊕, Re = 2.67 ± 0.11 R⊕. Having a density of 3.0 ± 0.8 g cm−3, TOI-561 b is the lowest density USP planet known to date. Our N-body simulations confirm the stability of the system and predict a strong, anti-correlated, long-term transit time variation signal between planets d and e. The unusual density of the inner super-Earth and the dynamical interactions between the outer planets make TOI-561 an interesting follow-up target.
We integrated clinical, genomic, and transcriptomic data from 224 primaries and 95 metastases from 289 patients to characterize progression of pancreatic ductal adenocarcinoma (PDAC). Driver gene ...alterations and mutational and expression-based signatures were preserved, with truncations, inversions, and translocations most conserved. Cell cycle progression (CCP) increased with sequential inactivation of tumor suppressors, yet remained higher in metastases, perhaps driven by cell cycle regulatory gene variants. Half of the cases were hypoxic by expression markers, overlapping with molecular subtypes. Paired tumor heterogeneity showed cancer cell migration by Halstedian progression. Multiple PDACs arising synchronously and metachronously in the same pancreas were actually intra-parenchymal metastases, not independent primary tumors. Established clinical co-variates dominated survival analyses, although CCP and hypoxia may inform clinical practice.
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•Higher cell cycle progression in PDAC metastases; increases with driver gene loss•Half of PDACs are hypoxic and are associated with subtypes and treatment response•Paired tumors show molecular conservation and Halstedian progression•Multiple PDACs arising in the same pancreas are intra-parenchymal metastases
Connor et al. molecularly characterize primary and metastatic PDAC and show conserved alterations between primary and metastatic lesions. Clinical features outperform molecular alterations in survival analyses, but cell cycle progression and hypoxia signatures may inform clinical practice.
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