We show that the Plebański-Demiański spacetime persists as a solution of general relativity when the theory is supplemented with both, a conformally coupled scalar theory and with quadratic curvature ...corrections. The quadratic terms are of two types and are given by quadratic combinations of the Riemann tensor as well as a higher curvature interaction constructed with a scalar field which is conformally coupled to quadratic terms in the curvature. The later is built in terms of a four-rank tensor Sμνλρ that depends on the Riemann tensor and the scalar field, and that transforms covariantly under local Weyl rescalings. Due to the generality of the Plebański-Demiański family, several new hairy black hole solutions are obtained in this higher curvature model. We pay particular attention to the C-metric spacetime and the stationary Taub-NUT metric, which in the hyperbolic case can be analytically extended leading to healthy, asymptotically AdS, wormhole configurations. Finally, we present a new general model for higher derivative, conformally coupled scalars, depending on an arbitrary function and that we have dubbed conformal K essence. We also construct spherically symmetric hairy black holes for these general models.
Myc oncoproteins are commonly upregulated in human cancers of different organ origins, stabilized by Aurora A, degraded through ubiquitin-proteasome pathway-mediated proteolysis, and exert oncogenic ...effects by modulating gene and protein expression. Histone deacetylases are emerging as targets for cancer therapy. Here we demonstrated that the class III histone deacetylase SIRT2 was upregulated by N-Myc in neuroblastoma cells and by c-Myc in pancreatic cancer cells, and that SIRT2 enhanced N-Myc and c-Myc protein stability and promoted cancer cell proliferation. Affymetrix gene array studies revealed that the gene most significantly repressed by SIRT2 was the ubiquitin-protein ligase NEDD4. Consistent with this finding, SIRT2 repressed NEDD4 gene expression by directly binding to the NEDD4 gene core promoter and deacetylating histone H4 lysine 16. Importantly, NEDD4 directly bound to Myc oncoproteins and targeted Myc oncoproteins for ubiquitination and degradation, and small-molecule SIRT2 inhibitors reactivated NEDD4 gene expression, reduced N-Myc and c-Myc protein expression, and suppressed neuroblastoma and pancreatic cancer cell proliferation. Additionally, SIRT2 upregulated and small-molecule SIRT2 inhibitors decreased Aurora A expression. Our data reveal a novel pathway critical for Myc oncoprotein stability, and provide important evidences for potential application of SIRT2 inhibitors for the prevention and therapy of Myc-induced malignancies.
Current staging methods for pancreatic cancer (PC) are inadequate, and biomarkers to aid clinical decision making are lacking. Despite the availability of the serum marker carbohydrate antigen 19.9 ...(CA19.9) for over two decades, its precise role in the management of PC is yet to be defined, and as a consequence, it is not widely used.
We assessed the relationship between perioperative serum CA19.9 levels, survival and adjuvant chemotherapeutic responsiveness in a cohort of 260 patients who underwent operative resection for PC.
By specifically assessing the subgroup of patients with detectable CA19.9, we identified potential utility at key clinical decision points. Low postoperative CA19.9 at 3 months (median survival 25.6 vs 14.8 months, P = 0.0052) and before adjuvant chemotherapy were independent prognostic factors. Patients with postoperative CA 19.9 levels >90 U/ml did not benefit from adjuvant chemotherapy (P = 0.7194) compared with those with a CA19.9 of ≤90 U/ml (median 26.0 vs 16.7 months, P = 0.0108). Normalization of CA19.9 within 6 months of resection was also an independent favorable prognostic factor (median 29.9 vs 14.8 months, P = 0.0004) and normal perioperative CA19.9 levels identified a good prognostic group, which was associated with a 5-year survival of 42%.
Perioperative serum CA19.9 measurements are informative in patients with detectable CA19.9 (defined by serum levels of >5 U/ml) and have potential clinical utility in predicting outcome and response to adjuvant chemotherapy. Future clinical trials should prioritize incorporation of CA19.9 measurement at key decision points to prospectively validate these findings and facilitate implementation.
Goethite (α-FeOOH) is dispersed throughout the earth’s surface, and its propensity to recrystallize in aqueous solutions determines whether this mineral is a source or sink for critical trace ...elements in the environment. Under reducing conditions, goethite commonly coexists with aqueous Fe(II) (Fe(II)aq), which accelerates recrystallization by coupled electron transfer and atom exchange. Quantifying the amount of the mineral phase that exchanges its structural Fe(III) atoms with Fe(II)aq is complicated by recrystallization models with untested assumptions of whether, and to what extent, the recrystallized portion of the mineral continues to interact with the solution. Here, we reacted nanoparticulate goethite with 57Fe-enriched Fe(II)aq and used atom probe tomography (APT) to resolve the three-dimensional distribution of Fe isotopes in goethite at the sub nm scale. We found that the 57Fe tracer isotope is enriched in the bulk structure (tens of nanometers deep), with some samples having 57Fe penetration throughout at a level that is similar to the isotopic composition of Fe(II)aq. This suggests that some particles undergo near-complete recrystallization. In other cases, however, the distribution of 57Fe is more heterogeneous and generally concentrates near the particle periphery. Nanoparticle encapsulation and subsequent APT can hence capture hidden recrystallization mechanisms which are critical to predicting mineral reactivity in aqueous solutions.
K-associated anemic disease of the fetus and newborn (K-ADFN) is a rare but life-threatening disease in which maternal alloantibodies cross the placenta and can mediate an immune attack on fetal red ...blood cells expressing the K antigen. A considerably more common disease, D-associated hemolytic disease of the fetus and newborn (D-HDFN), can be prophylactically treated using polyclonal α-D antibody preparations. Currently, no such prophylactic treatment exists for K-associated fetal anemia, and disease is usually treated with intrauterine blood transfusions. Here we review current understanding of the biology of K-associated fetal anemia, how the maternal immune system is sensitized to fetal red blood cells, and what is understood about potential mechanisms of prophylactic HDFN interventions. Given the apparent challenges associated with preventing alloimmunization, we highlight novel strategies for treating sensitized mothers to prevent fetal anemia that may hold promise not only for K-mediated disease, but also for other pathogenic alloantibody responses.
Purpose
Soft skills which are a combination of personal qualities and interpersonal skills that help an employer perform their job are an increasingly important concern to businesses and academia, ...the purpose of this paper is to determine how students ranked the importance of soft skills and compare their rankings to retailing and tourism management faculty and businesses.
Design/methodology/approach
A cross-sectional survey of students, faculty and industry leaders was conducted using an existing survey instrument validated by Crawford et al. (2011). Faculty who were members of retailing and tourism management professional organizations were solicited to participate in the study. Retailing and tourism management students from the researchers’ university were sent a link to complete the survey. All participants were asked to rank the order of importance of the soft skills and their characteristics.
Findings
Variations in the importance of soft skills were reported between the three groups. Variations in the importance of the soft skills characteristics were also identified between the students, faculty, and industry leaders. While communication was identified as the most important soft skill by all three sample groups, experiences was the least important for students and leadership was the least important for faculty and industry leaders.
Research limitations/implications
A limitation of the study was the variation in the sample sizes between the student, faculty, and industry sample. The strength of this study lies in the ability to provide evidence for the need to compare soft skills research results for retailing and tourism management students. Soft skills are found to be important to all three groups, but differences indicate faculty and industry need to work together to clarify exactly what soft skills students need to successfully compete for employment in the retailing and tourism management field.
Originality/value
As the work world continues to change, employers seek workers who have soft skills that support their knowledge base. While technical skills are a current part of educational curricula, soft skills need to be emphasized at the university level so that students gain expertise that prepare them to be successful in this changing workplace.
Purpose
Adolescent-disordered eating behaviours and attitudes (DEBA) are noted to be increasing in prevalence internationally. The aim of this study was to explore the DEBAs among Jamaican ...adolescents and identify those adolescents most at risk.
Methods
521 high school participants (females,
n
= 292), ages 11–19 years, completed measures assessing socio-demographic factors, self-esteem, symptoms of anxiety and depression, behavioural factors, and anthropometry. Weight-related behaviours and attitudes were explored using the Eating Attitudes Test (EAT-26).
Results
Thirty-one percent of participants reported engaging in at least one disordered eating behaviour, with bingeing as the most common. Female participants had significantly higher mean body mass index (
p
< 0.01) and mean EAT-26 score (
p
< 0.05) compared to males. Adolescents with EAT-26 score ≥ 20 were more desirous of being thinner (
p
< 0.01) and having a lighter skin complexion (
p
< 0.05). A greater proportion of adolescents with an EAT-26 score ≥ 20 had engaged in self-harm (
p
< 0.05), had smoked cigarettes (
p
< 0.05), had been sexually active (
p
< 0.01), and gave a history of sexual abuse (
p
< 0.01). Adolescents with overweight/obesity reported higher use of chemical weight manipulation (laxatives, diuretics, and diet pills) (
p
= 0.01).
Conclusions
Our data are consistent with the global figures showing both male and female adolescents endorsing disordered eating behaviours and attitudes (DEBAs). While this study highlights weight and shape dissatisfaction and associated DEBAs, it also raises the concern of an association with skin bleaching and elevated EAT-26 scores among Jamaican adolescents.
Level of evidence
Level V: cross-sectional descriptive study.
The serum/plasma proteome was explored for biomarkers to improve the diagnostic ability of CA19-9 in pancreatic adenocarcinoma (PC).
A Training Set of serum samples from 20 resectable and 18 stage IV ...PC patients, 54 disease controls (DCs) and 68 healthy volunteers (HVs) were analysed by surface-enhanced laser desorption and ionisation time-of-flight mass spectrometry (SELDI-TOF MS). The resulting protein panel was validated on 40 resectable PC, 21 DC and 19 HV plasma samples (Validation-1 Set) and further by ELISA on 33 resectable PC, 28 DC and 18 HV serum samples (Validation-2 Set). Diagnostic panels were derived using binary logistic regression incorporating internal cross-validation followed by receiver operating characteristic (ROC) analysis.
A seven-protein panel from the training set PC vs DC and from PC vs HV samples gave the ROC area under the curve (AUC) of 0.90 and 0.90 compared with 0.87 and 0.91 for CA19-9. The AUC was greater (0.97 and 0.99, P<0.05) when CA19-9 was added to the panels and confirmed on the validation-1 samples. A simplified panel of apolipoprotein C-I (ApoC-I), apolipoprotein A-II (ApoA-II) and CA19-9 was tested on the validation-2 set by ELISA, in which the ROC AUC was greater than that of CA19-9 alone for PC vs DC (0.90 vs 0.84) and for PC vs HV (0.96 vs 0.90).
A simplified diagnostic panel of CA19-9, ApoC-I and ApoA-II improves the diagnostic ability of CA19-9 alone and may have clinical utility.
Adjuvant chemotherapy improves survival for patients with resected pancreatic cancer. Elderly patients are under-represented in Phase III clinical trials, and as a consequence the efficacy of ...adjuvant therapy in older patients with pancreatic cancer is not clear. We aimed to assess the use and efficacy of adjuvant chemotherapy in older patients with pancreatic cancer.
We assessed a community cohort of 439 patients with a diagnosis of pancreatic ductal adenocarcinoma who underwent operative resection in centres associated with the Australian Pancreatic Cancer Genome Initiative.
The median age of the cohort was 67 years. Overall only 47% of all patients received adjuvant therapy. Patients who received adjuvant chemotherapy were predominantly younger, had later stage disease, more lymph node involvement and more evidence of perineural invasion than the group that did not receive adjuvant treatment. Overall, adjuvant chemotherapy was associated with prolonged survival (median 22.1 vs 15.8 months; P<0.0001). Older patients (aged ≥70) were less likely to receive adjuvant chemotherapy (51.5% vs 29.8%; P<0.0001). Older patients had a particularly poor outcome when adjuvant therapy was not delivered (median survival=13.1 months; HR 1.89, 95% CI: 1.27-2.78, P=0.002).
Patients aged ≥70 are less likely to receive adjuvant therapy although it is associated with improved outcome. Increased use of adjuvant therapy in older individuals is encouraged as they constitute a large proportion of patients with pancreatic cancer.
The N-Myc oncoprotein induces neuroblastoma, which arises from undifferentiated neuroblasts in the sympathetic nervous system, by modulating gene and protein expression and consequently causing cell ...differentiation block and cell proliferation. The class IIa histone deacetylase 5 (HDAC5) represses gene transcription, and blocks myoblast, osteoblast and leukemia cell differentiation. Here we showed that N-Myc upregulated HDAC5 expression in neuroblastoma cells. Conversely, HDAC5 repressed the ubiquitin-protein ligase NEDD4 gene expression, increased Aurora A gene expression and consequently upregulated N-Myc protein expression. Genome-wide gene expression analysis and protein co-immunoprecipitation assays revealed that HDAC5 and N-Myc repressed the expression of a common subset of genes by forming a protein complex, whereas HDAC5 and the class III HDAC SIRT2 independently repressed the expression of another common subset of genes without forming a protein complex. Moreover, HDAC5 blocked differentiation and induced proliferation in neuroblastoma cells. Taken together, our data identify HDAC5 as a novel co-factor in N-Myc oncogenesis, and provide the evidence for the potential application of HDAC5 inhibitors in the therapy of N-Myc-induced neuroblastoma and potentially other c-Myc-induced malignancies.
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