The Human Right to Science and Foundational Technologies

Feeney et al. (2018) make a valid argument for restrictions on the exclusivity of foundational technologies such as CRISPR. The issue of balancing intellectual property right with access to scientific and technological advancements is certainly not new. In our commentary, we argue that the human right to science offers a more concrete basis for governments to balance their competing commitments in promoting scientific development on the one hand, and ensuring benefit-sharing on the other, in ways that advance social justice under non-ideal conditions

Impact of target warhead and linkage vector on inducing protein degradation:comparison of Bromodomain and Extra-Terminal (BET) degraders derived from triazolodiazepine (JQ1) and tetrahydroquinoline (I-BET726) BET inhibitor scaffolds

The design of proteolysis-targeting chimeras (PROTACs) is a powerful small-molecule approach for inducing protein degradation. PROTACs conjugate a target warhead to an E3 ubiquitin ligase ligand via a linker. Here we examined the impact of derivatizing two different BET bromodomain inhibitors, triazolodiazepine JQ1 and the more potent tetrahydroquinoline I-BET726, via distinct exit vectors, using different polyethylene glycol linkers to VHL ligand VH032. Triazolodiazepine PROTACs exhibited positive cooperativities of ternary complex formation and were more potent degraders than tetrahydroquinoline compounds, which showed negative cooperativities instead. Marked dependency on linker length was observed for BET-degrading and cMyc-driven antiproliferative activities in acute myeloid leukemia cell lines. This work exemplifies as a cautionary tale how a more potent inhibitor does not necessarily generate more potent PROTACs and underscores the key roles played by the conjugation. The provided insights and framework for structure–activity relationships of bivalent degraders are anticipated to have wide future applicability

An assessment of financial sector rescue programmes

We analyse the wide array of rescue programmes adopted in several countries, following Lehman Brothers’ default in September 2008, in order to support banks and other financial institutions. We first provide an overview of the programmes, comparing their characteristics, magnitudes and participation rates across countries. We then consider the effects of the programmes on banks’ risk and valuation, looking at the behaviour of CDS premia and stock prices. We then proceed to analyse the issuance of government guaranteed bonds by banks, examining their impact on banks’ funding and highlighting undesired effects and distortions. Finally, we briefly review the recent evolution of bank lending to the private sector. We draw policy implications, in particular as regards the way of mitigating the distortions implied by such programmes and the need for an exit strategy.bank asset guarantees, capital injection, banks, financial sector, financial crisis, bank consolidation, bank mergers and acquisitions, event studies, government guaranteed bonds, credit crunch, exit strategy

Spatial Distribution of PM\u3csub\u3e2.5\u3c/sub\u3e-Related Premature Mortality in China

PM2.5 is a major component of air pollution in China and has a serious threat to public health. It is very important to quantify spatial characteristics of the health effects caused by outdoor PM2.5 exposure. This study analyzed the spatial distribution of PM2.5 concentration (45.9 μg/m3 national average in 2016) and premature mortality attributed to PM2.5 in cities at the prefectural level and above in China in 2016. Using the Global Exposure Mortality Model (GEMM), the total premature mortality in China was estimated to be 1.55 million persons, and the per capita mortality was 11.2 per 10,000 persons in the year 2016, resulting in higher estimates compared to the integrated exposure-response model. We assessed the premature mortality attributed to PM2.5 through common diseases, including ischemic heart disease (IHD), cerebrovascular disease (CEV), chronic obstructive pulmonary disease (COPD), lung cancer (LC), and lower respiratory infections (LRI). The premature mortality due to IHD and CEV accounted for 68.5% of the total mortality, and the per capita mortality (per 10,000 persons) for all ages due to IHD was 3.86, the highest among diseases. For the spatial distribution of disease-specific premature mortality, the top two highest absolute numbers of premature mortality associated with IHD, CEV, LC, and LRI, respectively, were found in Chongqing and Beijing. In 338 cities of China, we have found a significant positive spatial autocorrelation of per capita premature mortality, indicating the necessity of coordinated regional governance for an efficient control of PM2.5. Plain Language Summary Fine particulate matter (PM2.5) concentrations have increased in general, in most developing countries in recent decades. In China, PM2.5 pollution has become a major component of air pollution and has serious health impacts. To obtain a comprehensive understanding of the national health impacts of PM2.5 in China, we have used the Global Exposure Mortality Model (GEMM) to estimate the premature mortality associated with PM2.5 exposure in 338 cities in China at the prefectural level and above. In addition, we analyzed the spatial distribution of premature mortality attributed to PM2.5 for five diseases, including ischemic heart disease (IHD), cerebrovascular disease (CEV), chronic obstructive pulmonary disease (COPD), lung cancer (LC), and lower respiratory infections (LRI). Our study finds that the total premature mortality associated with PM2.5 exposure in China for 2016 was 1.55 million persons. The top two highest absolute numbers of premature mortality associated with IHD, CEV, LC, and LRI, respectively were found in Chongqing and Beijing. Furthermore, cities with high per capita premature mortality tended to be spatially connected with other cities with high per capita premature mortality, indicating the coordinated regional governance should be adopted to reduce the impact of PM2.5 on human health

Spatial Distribution of PM\u3csub\u3e2.5\u3c/sub\u3e-Related Premature Mortality in China

PM2.5 is a major component of air pollution in China and has a serious threat to public health. It is very important to quantify spatial characteristics of the health effects caused by outdoor PM2.5 exposure. This study analyzed the spatial distribution of PM2.5 concentration (45.9 μg/m3 national average in 2016) and premature mortality attributed to PM2.5 in cities at the prefectural level and above in China in 2016. Using the Global Exposure Mortality Model (GEMM), the total premature mortality in China was estimated to be 1.55 million persons, and the per capita mortality was 11.2 per 10,000 persons in the year 2016, resulting in higher estimates compared to the integrated exposure-response model. We assessed the premature mortality attributed to PM2.5 through common diseases, including ischemic heart disease (IHD), cerebrovascular disease (CEV), chronic obstructive pulmonary disease (COPD), lung cancer (LC), and lower respiratory infections (LRI). The premature mortality due to IHD and CEV accounted for 68.5% of the total mortality, and the per capita mortality (per 10,000 persons) for all ages due to IHD was 3.86, the highest among diseases. For the spatial distribution of disease-specific premature mortality, the top two highest absolute numbers of premature mortality associated with IHD, CEV, LC, and LRI, respectively, were found in Chongqing and Beijing. In 338 cities of China, we have found a significant positive spatial autocorrelation of per capita premature mortality, indicating the necessity of coordinated regional governance for an efficient control of PM2.5. Plain Language Summary Fine particulate matter (PM2.5) concentrations have increased in general, in most developing countries in recent decades. In China, PM2.5 pollution has become a major component of air pollution and has serious health impacts. To obtain a comprehensive understanding of the national health impacts of PM2.5 in China, we have used the Global Exposure Mortality Model (GEMM) to estimate the premature mortality associated with PM2.5 exposure in 338 cities in China at the prefectural level and above. In addition, we analyzed the spatial distribution of premature mortality attributed to PM2.5 for five diseases, including ischemic heart disease (IHD), cerebrovascular disease (CEV), chronic obstructive pulmonary disease (COPD), lung cancer (LC), and lower respiratory infections (LRI). Our study finds that the total premature mortality associated with PM2.5 exposure in China for 2016 was 1.55 million persons. The top two highest absolute numbers of premature mortality associated with IHD, CEV, LC, and LRI, respectively were found in Chongqing and Beijing. Furthermore, cities with high per capita premature mortality tended to be spatially connected with other cities with high per capita premature mortality, indicating the coordinated regional governance should be adopted to reduce the impact of PM2.5 on human health

Influencia de la calidad de servicio y confianza sobre la lealtad de los clientes en la florería Betania, Chiclayo 2018

La empresa Florería Betania, cuenta actualmente con una cartera de clientes importante; que ha sabido ganarse a través de diferentes factores que representan a dicha organización. Es por esa razón que en la presente investigación se desea conocer la influencia de la calidad de servicio y confianza sobre la lealtad de los clientes, con la finalidad de brindar dicha información a la empresa y al mismo tiempo enriquecer conocimientos. El propósito de la investigación es determinar la manera en que está influyendo la calidad de servicio y confianza en la lealtad de sus clientes, para que se pueda posicionar en el mercado empresarial y así mejoren en todos los aspectos como empresa para ganar un cliente satisfecho, tiene como objetivo general de este informe de tesis determinar la influencia de la calidad de servicio y la confianza sobre la lealtad en los clientes de Florería Betania Chiclayo; para esto se realizó una investigación de tipo descriptiva y a la vez cuantitativa, teniendo como resultado un nivel alto en la influencia que existe tanto en la calidad de servicio con lealtad y en la confianza con lealtad. Por ello se tuvo como resultado que es fundamental que el personal de la empresa esté siempre pendiente de lo que desea el cliente y cómo lo desea, y; así pueda quedar completamente satisfecho con su compra , realizándose la opción de recompra o recomendación con otras personas de su entorno para que la marca se posicione y de la mejor manera, lo cual se está dando de una manera positiva pero se debe seguir tr4abajando para obtener la total lealtad de los clientes, donde se concluye que sí existe una influencia de la calidad de servicio y confianza en la lealtad de los clientes en la Florería Betania