615 research outputs found
Chthamalus williamsi Chan & Cheang, 2015, sp. nov.
No full textChthamalus williamsi sp. nov. Figures 2–5 Material examined. Holotype. NMNS-006534-00001. Intertidal rocks (low shores, at the same tidal zone as Megabalanus volcano) at Shi-Ti-Ping, Hualien, Taiwan (23 ° 29.30 ’N, 121 ° 30.30 ’E, 12 May 2009). Paratype. NMNS-006534-00002. Cheng Gong, Taitung, Taiwan (23 °05.46’N, 121 ° 22.33 ’E, 0 2 Sep. 2008). Paratype. ASIZCR-000328. Cheng Gong, Taitung, Taiwan (23 °05.46’N, 121 ° 22.33 ’E, 0 2 Sep. 2008). Diagnosis. Shell conical; 6 plates, external surfaces white, smooth or with faint ribs; scutum equilateral triangular, tergal articular margin straight, external surface of scutum with horizontal striations; tergum triangular, scutal articular margin straight, spur blunt. Description. Shell small, about 3.0 mm basal diameter, conical; 6 plates (rostrum, carina, paired lateral and paired rostral-lateral; Fig. 2 A–D), externally white, surface smooth or with faint ribs, inner operculum pale orangecoloured; carina and rostrum with a pair of alae, carina short and wide, alae large; rostrum long and narrow, alae large; rostral-lateral triangular, interior surface with central mid rib, radii wide; lateral base wide, alae and radii present (Fig. 2 D); scutum white, triangular, tergal articular margin straight, perpendicular to basal margin, articular ridge not prominent, long with length extending 2 / 3 length of tergal articular margin, articular furrow narrow, deep, occludent margin inclined with fine teeth, scutal adductor scar oval, obvious, external surface of scutum with horizontal striations (Fig. 2 E, F); tergum white, triangular, scutal articular margin straight, extending down to spur, spur blunt, wide, about ½ width of basal margin, articular furrow wide, shallow, basal margin slightly concave (Fig. 2 E, F), 5 fine depressor crests at basal margin, external surface striated. Cirrus I without conical spines on dorsal surface, posterior ramus 5 -segmented, anterior ramus 6 -segmented (Fig. 3 A), both rami with serrulate setae, setae without basal guard (Fig. 4 A–C); cirrus II, anterior ramus 5 - segmented, posterior ramus 7 -segmented (Fig. 3 B), both rami with 2 types of serrulate setae, bidentate and plumose setae, all setae without basal guard (Figs 4 D–F, 5 K, L); cirrus III with rami equal length, anterior ramus 14 -segmented, posterior ramus 12 -segmented (Figs 3 C, 4 G), intermediate segments of cirrus III composed of 5 pairs of long serrulate setae (Fig. 4 H, I); cirrus IV with anterior ramus 14 -segmented, posterior ramus 15 - segmented (Fig. 3 D); cirrus V with anterior ramus 18 -segmented, posterior ramus 15 -segmented (Fig. 3 E), intermediate segments of both rami with 3 pairs of long serrulate setae and 2 pairs of shorter setae (Fig. 4 J); cirrus VI with anterior ramus 19 -segmented, posterior ramus 17 -segmented, intermediate segments of anterior and posterior rami composed of 3 pairs of long serrulate setae and 2 pairs of shorter setae (Fig. 4 K); penis long, slender, sparse setae along length, tip with dense bundle of setae (Fig. 5 I, J). Maxilla bilobed, serrulate setae on both lobes (Fig. 5 A, B); maxillule notched, 3 large setae above notch, 16 setae below notch (Fig. 5 C, D); mandible with 4 teeth, fourth bidentate, lower margin straight, with 14 setae, inferior angle with pair of large setae (Fig. 5 E, F); labrum concave, notch absent, dense setae at mid region of cutting margin, latter with numerous fine teeth (Fig. 5 G, H). Etymology. Chthamalus williamsi is named in honour of Prof. Gray A. Williams, Director of the Swire Institute of Marine Sciences, School of Biological Science, the University of Hong Kong, for life-long friendship and mentorship with the first author and for his contributions to the intertidal ecology in the South China Sea. Distribution. Chthamalus williamsi sp. nov. is common inside crevices of the mid shore of the intertidal zone, and on the shell surfaces of the barnacle Megabalanus volcano (Pilsbry, 1916) and M. tintinnabulum (Linnaeus, 1758) on low shores of the eastern waters of Taiwan. Chthamalus williamsi has not been identified previously from Taiwan as it is not easily spotted, due to its small size and low shore location. This species is absent from the N and NE coasts of Taiwan although intensive sampling was conducted (Fig. 1), suggesting its distribution may be associated with the Kuroshio Current. Molecular analysis. From both maximum likelihood and Bayesian inference trees of a COI region, Chthamalus williamsi shows a distinct divergence from C. challengeri, C. dalli, C. moro, C. malayensis and C. sinensis (sequence divergence> 0.13 K 2 P distance from all the Chthamalus species compared; Table 1). Chthamalus sinensis and C. neglectus grouped in the same clade, suggesting C. neglectus is a synonym of C. sinensis (see Liu & Ren 2007 for synonyms of C. neglectus and C. sinensis).Published as part of Chan, Benny K. K. & Cheang, Chi Chiu, 2015, A new Chthamalus (Crustacea: Cirripedia) from the challengeri subgroup on Taiwan rocky intertidal shores, pp. 547-558 in Zootaxa 4000 (5) on pages 549-550, DOI: 10.11646/zootaxa.4000.5.4, http://zenodo.org/record/23674
Lights and Shadows in Immuno-Oncology Drug Development.
No full textThe rapidly evolving landscape of immuno-oncology (IO) is redefining the treatment of a number of cancer types. IO treatments are becoming increasingly complex, with different types of drugs emerging beyond checkpoint inhibitors. However, many of the new drugs either do not progress from phase I-II clinical trials or even fail in late-phase trials. We have identified at least five areas in the development of promising IO treatments that should be redefined for more efficient designs and accelerated approvals. Here we review those critical aspects of IO drug development that could be optimized for more successful outcome rates in all cancer types. It is important to focus our efforts on the mechanisms of action, types of response and adverse events of these novel agents. The use of appropriate clinical trial designs with robust biomarkers of response and surrogate endpoints will undoubtedly facilitate the development and subsequent approval of these drugs. Further research is also needed to establish biomarker-driven strategies to select which patients may benefit from immunotherapy and identify potential mechanisms of resistance
Changes in expression of genes representing key biologic processes after neoadjuvant chemotherapy in breast cancer, and prognostic implications in residual disease
No full textPurpose: The primary aim was to derive evidence for or against the clinical importance of several biologic processes in patients treated with neoadjuvant chemotherapy (NAC) by assessing expression of selected genes with prior implications in prognosis or treatment resistance. The secondary aim was to determine the prognostic impact in residual disease of the genes' expression. Experimental Design: Expression levels of 24 genes were quantified by NanoString nCounter on formalin-fixed paraffinembedded residual tumors from 126 patients treated with NAC and 56 paired presurgical biopsies. The paired t test was used for testing changes in gene expression, and Cox regression and penalized elastic-net Cox Regression for estimating HRs. Results: After NAC, 12 genes were significantly up- and 8 downregulated. Fourteen genes were significantly associated with time to recurrence in univariable analysis in residual disease. In a multivariable model, ACACB, CD3D, MKI67, and TOP2A added prognostic value independent of clinical ER-, PgR-, and HER2- status. In ER+/HER2- patients, ACACB, PAWR, and ERBB2 predicted outcome, whereas CD3D and PAWR were prognostic in ER-/HER2- patients. By use of elastic-net analysis, a 6-gene signature (ACACB, CD3D, DECORIN, ESR1, MKI67, PLAU) was identified adding prognostic value independent of ER, PgR, and HER2. Conclusions: Most of the tested genes were significantly enriched or depleted in response to NAC. Expression levels of genes representing proliferation, stromal activation, metabolism, apoptosis, stemcellness, immunologic response, and Ras-ERK activation predicted outcome in residual disease. Themultivariable gene models identified could, if validated, be used to identify patients needing additional post-neoadjuvant treatment to improve prognosis
IgG4-Related Kidney Disease: A Curious Case of Interstitial Nephritis with Hypocomplementemia
No full textIgG4-related kidney disease has been relatively newly recognized over the last two decades as a combination of an autoimmune and allergic disorder, with elevated serum IgG4 level and hypocomplementemia among its characteristic features. Here we report the case of a man with interstitial nephritis presenting with acute kidney injury and hypocomplementemia but normal serum IgG4 level and provide a literature review of IgG4-related kidney disease. This case highlights the importance of IgG4-related kidney disease as an important differential diagnosis in any patient presenting with a clinical syndrome mimicking acute interstitial nephritis with hypocomplementemia. A high index of suspicion with a low threshold for performing a native kidney biopsy would be paramount as patients do respond well to corticosteroid therapy
Prognostic Value of Intrinsic Subtypes in Hormone Receptor–Positive Metastatic Breast Cancer Treated With Letrozole With or Without Lapatinib
No full textIMPORTANCE: The value of the intrinsic subtypes of breast cancer (luminal A, luminal B, human epidermal growth factor receptor 2 [currently known as ERBB2, but referred to as HER2 in this study]-enriched, and basal-like) in the metastatic setting is currently unknown. OBJECTIVE: To evaluate the association of the intrinsic subtypes of breast cancer with outcome and/or benefit in hormone receptor (HR)-positive metastatic breast cancer. DESIGN, SETTING, AND PARTICIPANTS: Unplanned retrospective analysis of 821 tumor samples (85.7% primary and 14.3% metastatic) from the EGF30008 phase 3 clinical trial (NCT00073528), in which postmenopausal women with HR-positive invasive breast cancer and no prior therapy for advanced or metastatic disease were randomized to letrozole with or without lapatinib, an epidermal growth factor receptor (EGFR)/HER2 tyrosine kinase inhibitor. Tumor samples were classified into each subtype using the research-based PAM50 classifier. Prior neoadjuvant/adjuvant antiestrogen therapy was allowed. Patients with extensive symptomatic visceral disease were excluded. Treatment effects were evaluated using interaction tests. MAIN OUTCOMES AND MEASURES: Primary and secondary end points were progression-free survival and overall survival. RESULTS: The median (range) age was 62 (31-94) years. Intrinsic subtype was the strongest prognostic factor independently associated with progression-free survival and overall survival in all patients, and in patients with HER2-negative (n = 644) or HER2-positive (n = 157) diseases. Median progression-free survival differed across the intrinsic subtypes of clinically HER2-negative disease: luminal A (16.9 [95% CI, 14.1-19.9] months), luminal B (11.0 [95% CI, 9.6-13.6] months), HER2-enriched (4.7 [95% CI, 2.7-10.8] months), and basal-like (4.1 [95% CI, 2.5-13.8] months). Median OS also differed across the intrinsic subtypes: luminal A (45 [95% CI, 41-not applicable {NA}] months), luminal B (37 [95% CI, 31-42] months), HER2-enriched (16 [95% CI, 10-NA] months), and basal-like (23 [95% CI, 12-NA] months). Patients with HER2-negative/HER2-enriched disease benefited from lapatinib therapy (median PFS, 6.49 vs 2.60 months; progression-free survival hazard ratio, 0.238 [95% CI, 0.066-0.863]; interaction P = .02). CONCLUSIONS AND RELEVANCE: This is the first study to reveal an association between intrinsic subtype and outcome in first-line HR-positive metastatic breast cancer. Patients with HR-positive/HER2-negative disease with a HER2-enriched profile may benefit from lapatinib in combination with endocrine therapy. The clinical value of intrinsic subtyping in hormone receptor-positive metastatic breast cancer warrants further investigation, but patients with luminal A/HER2-negative metastatic breast cancer might be good candidates for letrozole monotherapy in the first-line setting regardless of visceral disease and number of metastases
Does political uncertainty and political ideology place a discount on the M&A premiums?
No full textMestrado Bolonha em FinançasThis paper aims to study the relationship between political uncertainty and M&A
premium, with emphasis on close calls, political ideology, and political polarization of
extreme political parties. We cover a dataset from 2000 to 2022, covering 1646
announced deals in 29 different counties. Our results suggest that ideology can
significantly lower the M&A premium in countries that lean more to the right,
corresponding to a higher ideology variable. Overall, our findings support the argument
that investors place a discount on the premiums in M&A deals on account of the political
uncertainty of the target nation.Esta tese tem como objetivo estudar a relação entre a incerteza política e o prémio em
fusões e aquisições (M&A), com ênfase em disputas eleitorais renhidas, ideologia política
e polarização política de partidos políticos extremos. Analisamos um conjunto de dados
de 2000 a 2022, abrangendo 1646 negócios anunciados em 29 países diferentes. Os nossos
resultados sugerem que a ideologia pode diminuir significativamente o prémio de M&A
em países que tendem mais para a direita, correspondendo a uma ideologia mais forte. No
geral, as nossas conclusões apoiam o argumento de que os investidores aplicam um
desconto nos prémios em negócios de M&A devido à incerteza política do país-alvo.info:eu-repo/semantics/publishedVersio
Does political uncertainty and political ideology place a discount on the M&A premiums?
No full textMestrado Bolonha em FinançasThis paper aims to study the relationship between political uncertainty and M&A
premium, with emphasis on close calls, political ideology, and political polarization of
extreme political parties. We cover a dataset from 2000 to 2022, covering 1646
announced deals in 29 different counties. Our results suggest that ideology can
significantly lower the M&A premium in countries that lean more to the right,
corresponding to a higher ideology variable. Overall, our findings support the argument
that investors place a discount on the premiums in M&A deals on account of the political
uncertainty of the target nation.Esta tese tem como objetivo estudar a relação entre a incerteza política e o prémio em
fusões e aquisições (M&A), com ênfase em disputas eleitorais renhidas, ideologia política
e polarização política de partidos políticos extremos. Analisamos um conjunto de dados
de 2000 a 2022, abrangendo 1646 negócios anunciados em 29 países diferentes. Os nossos
resultados sugerem que a ideologia pode diminuir significativamente o prémio de M&A
em países que tendem mais para a direita, correspondendo a uma ideologia mais forte. No
geral, as nossas conclusões apoiam o argumento de que os investidores aplicam um
desconto nos prémios em negócios de M&A devido à incerteza política do país-alvo.info:eu-repo/semantics/publishedVersio
Dissecting the predictive value of MAPK/AKT/estrogen-receptor phosphorylation axis in primary breast cancer to treatment response for tamoxifen over exemestane: a Translational Report of the Intergroup Exemestane Study (IES)-PathIES
No full textPurpose
The prognostic and predictive values of the MAPK/AKT/ERα phosphorylation axis (pT202/T204MAPK, pT308AKT, pS473AKT, pS118ERα and pS167ERα) in primary tumours were assessed to determine whether these markers can differentiate between patient responses for switching adjuvant endocrine therapy after 2–3 years from tamoxifen to exemestane and continued tamoxifen monotherapy in the Intergroup Exemestane Study (IES).
Methods
Of the 4724 patients in IES, 1506 were managed in a subset of centres (N = 89) participating in PathIES. These centres recruited 1282 (85%, 1282/1506) women into PathIES of whom 1036 had phospho-marker data. All phospho-markers were analysed by immunohistochemistry staining. Multivariable Cox proportional hazards models of the phospho-markers for disease-free survival (DFS) and overall survival (OS) were adjusted for clinicopathological factors. Treatment effects on the biomarker expression were determined by interaction tests. Benjamini–Hochberg adjustment for multiple testing with a false discovery rate of 10% was applied (pBH).
Results
Phospho-T202/T204MAPK, pS118ERα and pS167ERα were all found to be correlated (pBH = 0.0002). These markers were not associated with either DFS or OS when controlling for the established clinicopathological factors. Interaction terms between the phospho-markers and treatment strategies for either DFS or OS were not statistically significant (pBH > 0.05 for all).
Conclusions
This PathIES study confirmed previously described associations between the phosphorylation site markers of AKT, MAPK and ERα activity in postmenopausal breast cancer patients. No prognostic correlations between the phosphorylation markers and clinical outcome were found, nor were they predictive for clinical outcomes among patients who switched therapy over those treated with tamoxifen alone
Hedge Portfolios in Markets with Price Discontinuities
No full textWe consider a market consisting of multiple assets under jump-diffusion dynamics with European style options written on these assets. It is well-known that such markets are incomplete in the Harrison and Pliska sense. We derive a pricing relation by adopting a Radon-Nikodym derivative based on the exponential martingale of a correlated Brownian motion process and a multivariate compound Poisson process. The parameters in the Radon-Nikodym derivative define a family of equivalent martingale measures in the model, and we derive the corresponding integro-partial differential equation for the option price. We also derive the pricing relation by setting up a hedge portfolio containing an appropriate number of options to "complete" the market. The market prices of jump-risks are priced in the hedge portfolio and we relate these to the choice of the parameters in the Radon-Nikodym derivative used in the alternative derivation of the integro-partial differential equation.incomplete markets; equivalent martingale measure; compound Poisson processes; Radon-Nikodym derivative; multi-asset options; integro-partial differential equation
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