The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Social disclosure and cost of equity in public companies in Brazil

Esta pesquisa tem por objetivo analisar a relação entre o nível de social disclosure e o custo de capital próprio em companhias abertas no Brasil. Assume-se a hipótese de que os programas sociais externos promovidos ou apoiados pelas empresas contribuem para a construção da imagem reputacional das organizações, compensando as externalidades, trazendo benefícios sob o ponto de vista econômico, pela relação negativa com o custo do capital. Para testar essa hipótese, foram coletados e analisados os relatórios de responsabilidade social de 83 empresas listadas na Bolsa de Valores, Mercadorias e Futuros de São Paulo (BM&FBovespa), no período de 2005 a 2009. Para avaliação do nível de social disclosure das empresas analisadas, foi utilizado um índice composto de 13 indicadores. O custo de capital próprio foi ajustado ao risco mediante o Capital Asset Pricing Model (CAPM) e testado por meio de regressão com dados em painel com efeitos fixos seccionais. Os resultados evidenciam que há relação negativa entre custo de capital próprio e nível de social disclosure, indicando, para o mercado acionário brasileiro, uma forma semiforte de eficiência de mercado. _________________________________________________________________________________ ABSTRACTThis study aims to analyze the relationship between the level of social disclosure and the cost of equity in public companies in Brazil. The hypothesis is that external social programs promoted or supported by a company increase the organization's reputation, compensate for externalities and bring economic benefits through the negative relationship with the cost of equity. To test this hypothesis, social responsibility reports of 83 companies listed on the São Paulo Stock, Mercantile and Futures Exchanges (Bolsa de Valores, Mercadorias e Futuros de São Paulo - BM&FBovespa) from the period 2005-2009 were collected and analyzed. A composite index of 13 indicators was used to evaluate the social disclosure level of the companies analyzed. The cost of equity was risk-adjusted using the capital asset-pricing model (CAPM) and regression tested using panel data with cross-sectional fixed effects. The results show a negative relationship between the cost of equity and level of social disclosure, indicating that the Brazilian stock market has a semi-strong form of market efficiency

When is two really company?: the effects of competition and regulation on corporate governance

In this paper we bring together agency, stakeholder, institutional and resource-dependence theories to study the direct and interactive effects of country regulation and competition on two dimensions of corporate governance: the overall quality of corporate governance of firms in a country, and firm-to-firm variations in corporate governance. Interactive conditions are more representative of the real-world context of corporate governance, and the contradictory pressures that firms face in such interactive conditions are better explained through the use of multiple theories of corporate governance. Using a dataset that spans 15 countries and includes 463 firms, we find that firm corporate governance is better in conditions where either regulation or competition is well-developed, by comparison with interactive conditions. We also find that while regulation enhances within- country convergence, it is likely that competition serves to enhance across-country convergence

cJUN N-terminal kinase (JNK) activation mediates islet amyloid-induced beta cell apoptosis in cultured human islet amyloid polypeptide transgenic mouse islets

Aims/hypothesisAggregation of human islet amyloid polypeptide (hIAPP) as islet amyloid is associated with increased beta cell apoptosis and reduced beta cell mass in type 2 diabetes. Islet amyloid formation induces oxidative stress, which contributes to beta cell apoptosis. The cJUN N-terminal kinase (JNK) pathway is a critical mediator of beta cell apoptosis in response to stress stimuli including oxidative stress and exogenous application of hIAPP. We determined whether amyloid formation by endogenous hIAPP mediates beta cell apoptosis through JNK activation and downstream signalling pathways.MethodshIAPP transgenic and non-transgenic mouse islets were cultured for up to 144 h in 16.7 mmol/l glucose to induce islet amyloid in the presence or absence of the amyloid inhibitor Congo Red or a cell-permeable JNK inhibitor. Amyloid, beta cell apoptosis, JNK signalling and activation of downstream targets in the intrinsic and extrinsic apoptotic pathways were measured.ResultsJNK activation occurred with islet amyloid formation in hIAPP transgenic islets after 48 and 144 h in culture. Neither high glucose nor the hIAPP transgene alone was sufficient to activate JNK independent of islet amyloid. Inhibition of islet amyloid formation with Congo Red reduced beta cell apoptosis and partially decreased JNK activation. JNK inhibitor treatment reduced beta cell apoptosis without affecting islet amyloid. Islet amyloid increased mRNA levels of markers of the extrinsic (Fas, Fadd) and intrinsic (Bim [also known as Bcl2l11]) apoptotic pathways, caspase 3 and the anti-apoptotic molecule Bclxl (also known as Bcl2l1) in a JNK-dependent manner.Conclusions/interpretationIslet amyloid formation induces JNK activation, which upregulates predominantly pro-apoptotic signals in both extrinsic and intrinsic pathways, resulting in beta cell apoptosis.<br /

Matrix Metalloproteinase-9 reduces islet amyloid formation by degrading islet amyloid polypeptide

Deposition of islet amyloid polypeptide (IAPP) as amyloid is a pathological hallmark of the islet in type 2 diabetes, which is toxic to &beta;-cells. We previously showed that the enzyme neprilysin reduces islet amyloid deposition and thereby reduces &beta;-cell apoptosis, by inhibiting fibril formation. Two other enzymes, matrix metalloproteinase (MMP)-2 and MMP-9, are extracellular gelatinases capable of degrading another amyloidogenic peptide, A&beta;, the constituent of amyloid deposits in Alzheimer disease. We therefore investigated whether MMP-2 and MMP-9 play a role in reducing islet amyloid deposition. MMP-2 and MMP-9 mRNA were present in mouse islets but only MMP-9 activity was detectable. In an islet culture model where human IAPP (hIAPP) transgenic mouse islets develop amyloid but nontransgenic islets do not, a broad spectrum MMP inhibitor (GM6001) and an MMP-2/9 inhibitor increased amyloid formation and the resultant &beta;-cell apoptosis. In contrast, a specific MMP-2 inhibitor had no effect on either amyloid deposition or &beta;-cell apoptosis. Mass spectrometry demonstrated that MMP-9 degraded amyloidogenic hIAPP but not nonamyloidogenic mouse IAPP. Thus, MMP-9 constitutes an endogenous islet protease that limits islet amyloid deposition and its toxic effects via degradation of hIAPP. Because islet MMP-9 mRNA levels are decreased in type 2 diabetic subjects, islet MMP-9 activity may also be decreased in human type 2 diabetes, thereby contributing to increased islet amyloid deposition and &beta;-cell loss. Approaches to increase islet MMP-9 activity could reduce or prevent amyloid deposition and its toxic effects in type 2 diabetes