Olaparib in combination with pegylated liposomal doxorubicin for platinum-resistant ovarian cancer regardless of BRCA status: a GEICO phase II trial (ROLANDO study)

Inhibidor de PARP; Olaparib; Càncer d'ovari recurrent resistent al platíInhibidor de PARP; Olaparib; Cáncer de ovario recurrente resistente al platinoPARP inhibitor; Olaparib; Platinum-resistant recurrent ovarian cancerBackground There is limited evidence for the benefit of olaparib in platinum-resistant ovarian cancer (PROC) patients with BRCA wild-type tumors. This study investigated whether this combination of a DNA-damaging chemotherapy plus olaparib is effective in PROC regardless BRCA status. Patients and methods Patients with high-grade serous or endometrioid ovarian carcinoma and one previous PROC recurrence were enrolled regardless of BRCA status. Patients with ≤4 previous lines (up to 5 in BRCA-mut) with at least one previous platinum-sensitive relapse were included; primary PROC was allowed only in case of BRCA-mut. Patients initially received six cycles of olaparib 300 mg b.i.d. (biduum) + intravenous pegylated liposomal doxorubicin (PLD) 40 mg/m2 (PLD40) every 28 days, followed by maintenance with olaparib 300 mg b.i.d. until progression or toxicity. The PLD dose was reduced to 30 mg/m2 (PLD30) due to toxicity. The primary endpoint was progression-free survival (PFS) at 6 months (6m-PFS) by RECIST version 1.1. A proportion of 40% 6m-PFS or more was considered of clinical interest. Results From 2017 to 2020, 31 PROC patients were included. BRCA mutations were present in 16%. The median of previous lines was 2 (range 1-5). The overall disease control rate was 77% (partial response rate of 29% and stable disease rate of 48%). After a median follow-up of 10 months, the 6m-PFS and median PFS were 47% and 5.8 months, respectively. Grade ≥3 treatment-related adverse events occurred in 74% of patients, with neutropenia/anemia being the most frequent. With PLD30 serious AEs were less frequent than with PLD40 (21% versus 47%, respectively); moreover, PLD30 was associated with less PLD delays (32% versus 38%) and reductions (16% versus 22%). Conclusions The PLD–olaparib combination has shown significant activity in PROC regardless of BRCA status. PLD at 30 mg/m2 is better tolerated in the combination.This work was supported by Grupo Español de Investigación en Cáncer de Ovario (GEICO) (no grant number). AstraZeneca provided olaparib and awarded a grant to GEICO (no grant number) to pay the costs of the study but did not take part in the conduct of the current clinical trial or in the analysis and interpretation of the results. Pegylated ribosomal doxorubicin was provided by the sites according to local standard procedures

Lepra - Algunos aspectos Inmunológicos -

252 patients with Leprosy were studied. 108 males and 44 females with Lepromatous Leprosy, 48 males and 52 females with Tuberculoid Leprosy. The following studies were performed in their sera: electrophoretic pattern, quantification of circulating levels of C3. IgG, IgA and IgM. No specific electrophoretic pattern was seen. only the gamma fraction was elevated and this alteration was statiscally significative in Lepromatous Leprosy. IgG and IgM levels were elevated in Lepromatous Leprosy, this alteration is statistically significative. IgA appears slightly elevated in both typesof Leprosy. No alteration in the level of circulating C3 was seen.Se estudiaron 252 pacientes con Lepra: 156 hombres y 96 mujeres. 108 hombres y 48 mujeres con Lepra Lepromatosa; 48 hombres y 52 mujeres con Lepra Tuberculoide. En esta muestra se estudiaron su patrón electroforético. la concentración de C3 y los niveles circulantes de IgG, IgA e IgM. Se  encontró que no existe un patrón definido electroforético que pueda asociarse con la Lepra, solo la fracción gamma muestra niveles altos en Lepra Lepromatosa y esta alteración comparada con la población general tiene significancia estadística. Unicamente la IgG e IgM muestran aumentos considerables con significación estadística para Lepra Lepromatosa. IgA se encuentra aumentada en los dos tipos de Lepra. No se encontró ninguna alteración en los niveles circulantes de C3

Economic Impact of Climate Determinants on Rice Farmlands in Davao Region, Philippines

Agriculture contributes largely to the economic growth of developing countries such as the Philippines. However, it is highly dependent on climate. The impending changes in climatic variables thus pose questions about its economic impacts on agricultural crops such as rice. There has been no study yet on the quantified positive or negative impact of changing weather patterns on the rice farmlands of Davao Region, Southern Philippines. Thus, this study used the Ricardian model in estimating the marginal effect of significant weather variables on the net revenue per hectare of rice farmlands in Davao Region. Farm net revenue per hectare was regressed on socio-demographic variables and on weather variables that affect rice growth, namely: rainfall, air temperature, air humidity, and wind speed. Primary survey on 44 rice farm households was conducted in 2015 for the socio-demographic variables and the computation of the farm net revenue per hectare, while secondary data for 2015 on the weather variables were obtained from the Philippine Atmospheric, Geophysical and Astronomical Services Administration (PAGASA) website. Results showed that air temperature and air humidity significantly affect the net revenue per hectare. Specifically, when air temperature increases beyond 27.03 °C, farm net revenue per hectare decreases. Farm net revenue also decreases when air humidity goes lower than 84.66%. Currently, the average air temperature and air humidity in the Davao Region are 26.75 °C and 85.18%, respectively. A unit increase in air temperature from the current average value reduces farm net revenue by PhP 116,420.50 per hectare, while a unit increase in air humidity raises farm net income by PhP 8,168.00 per hectare. This study recommends further educating people, particularly rice farmers, on mitigating the effects of changing weather conditions. Strategies and policies are crucial in order for farmers to adapt to these changing conditions

Recent variability of the global ocean carbon sink

We present a new observation-based estimate of the global oceanic carbon dioxide (CO2) sink and its temporal variation on a monthly basis from 1998 through 2011 and at a spatial resolution of 1×1. This sink estimate rests upon a neural network-based mapping of global surface ocean observations of the partial pressure of CO2 (pCO2) from the Surface Ocean CO2 Atlas database. The resulting pCO2 has small biases when evaluated against independent observations in the different ocean basins, but larger randomly distributed differences exist particularly in high latitudes. The seasonal climatology of our neural network-based product agrees overall well with the Takahashi et al. (2009) climatology, although our product produces a stronger seasonal cycle at high latitudes. From our global pCO2 product, we compute a mean net global ocean (excluding the Arctic Ocean and coastal regions) CO2 uptake flux of −1.42 ± 0.53 Pg C yr−1, which is in good agreement with ocean inversion-based estimates. Our data indicate a moderate level of interannual variability in the ocean carbon sink (±0.12 Pg C yr−1, 1𝜎) from 1998 through 2011, mostly originating from the equatorial Pacific Ocean, and associated with the El Nino–Southern Oscillation. Accounting for steady state riverine and Arctic Ocean carbon fluxes our estimate further implies a mean anthropogenic CO2 uptake of −1.99 ± 0.59 Pg C yr−1 over the analysis period. From this estimate plus the most recent estimates for fossil fuel emissions and atmospheric CO2 accumulation, we infer a mean global land sink of −2.82 ± 0.85 Pg C yr−1 over the 1998 through 2011 period with strong interannual variation

Aplicación de la RSE al proceso de desionización para producción de agua grado I-II y III en la empresa purificación y análisis de fluidos Ltda.

Tablas, graficasProponer el desarrollo de una herramienta de mejora ambiental para mitigar los efectos ambientales causados por la producción de agua desionizada grado I-II y III, basada en la norma SGE 21 en su numeral 6.6. La ISO 14000, que agrupa todos los estándares para el manejo responsable que las empresas le dan al medio ambiente; y la norma ISO 14001, la cual está dirigida a las personas, a la manera en que éstas se relacionan con los dispositivos, con las herramientas necesarias para su tarea en el entorno laboral, con los residuos, los cuales no siempre son tan evidentes, entre otros, se formula un proceso que permite manejar responsablemente los desechos generados por la planta de purificación de agua. También se trabajará como herramienta de verificación la norma ISO 19011, que proporcionará los parámetros y reglamentación del proceso en cuestión para las auditorías de seguimiento y mejora continúa. Las referencias para la medición de la calidad del producto y su residuo se tomarán de la norma USP.No Abstrac

Measuring the Economic Impact of Weather Determinants on Aquaculture in the Davao Region, Philippines

Aquaculture is an important determinant of economic growth in the Davao Region in the Southern Philippines because it contributes towards increasing employment and agribusiness development opportunities. However, the industry faces various issues that affect farm productivity. One of these challenges pertains to welfare effects emanating from changing patterns of weather variables. Hence, this research aimed to measure the impact of weather determinants on aquaculture production’s net income based on surveyed farms in the Davao Region. Based on the Ricardian approach, our econometric model specifies the dependent variable as net income (PhP/ha) and this is a function of weather variables such as precipitation, humidity, and agro-climatic and socio-demographic variables. From the results, weather and agro-climatic variability have statistically significant effects on aquaculture’s net income. More specifically, a unit increase in the standard deviation of rain value increases net income by PhP12,730. However, an increase in one standard deviation of average air humidity decreased net income by approximately PhP2,940. Finally, unit increases in the standard deviation of soil moisture and soil temperature translate to increases in net income by approximately PhP16,150 and PhP16,170. Thus, given the results, strategies that would enable aquaculture farmers to mitigate and adapt to changing weather conditions should be implemented. Also, weather stations should be updated and upgraded in order to provide accurate readings and forecasts so that aquaculture farmers’ decision making will be improved with regards to their farm practices

On the thermodynamics of the Swift–Hohenberg theory

We present the microbalance including the microforces, the first- and second-order microstresses for the Swift–Hohenberg equation concomitantly with their constitutive equations, which are consistent with the free-energy imbalance. We provide an explicit form for the microstress structure for a free-energy functional endowed with second-order spatial derivatives. Additionally, we generalize the Swift–Hohenberg theory via a proper constitutive process. Finally, we present one highly resolved three-dimensional numerical simulation to demonstrate the particular form of the resulting microstresses and their interactions in the evolution of the Swift–Hohenberg equation

Active flux seasonality of the small dominant migratory crustaceans and mesopelagic fishes in the Gulf of California during June and October

The biological carbon pump is the process that transports carbon vertically out of the mixed layer in the ocean. Besides the sinking flux of organic particles, active flux due to the daily vertical migration of zooplankton and micronekton promotes a significant carbon transport not fully accounted for or understood in the world’s oceans. The diversity and abundance of epipelagic and mesopelagic species in the Gulf of California has been extensively studied, but the role of micronekton in carbon export has not yet been investigated. We studied the carbon flux promoted by juvenile and adult mesopelagic fishes and crustaceans (Decapoda and Euphausiidae) during the transition from the cold to warm period (June) and the onset of the warm season (October) in 2018. We provide the first estimation of migrant biomass and respiratory flux of the most abundant migratory species of mesopelagic fishes, decapods and euphausiids in the Gulf of California. The micronekton species collected accounted for a large biomass of mesopelagic fishes and pelagic crustaceans. The average migrant biomass estimates were 151.5 ± 101.2 mg C·m−2 during June and 90.9 ± 75.3 mg C·m−2 during October. The enzymatic activity of the electron transfer system (ETS) was measured as an estimate of their respiratory rates. Average specific ETS activity was significantly different between fishes and decapods, and between fishes and euphausiids (p < 0.05). The respiratory flux of fishes was predominant in the Gulf of California, followed by pelagic decapods and euphausiids. Seasonal changes in respiratory flux were observed for fishes (June: 6.1 ± 1.5 mg C·m−2·d−1; October: 3.2 ± 1.8 mg C·m−2·d−1) and decapods (June: 0.4 mg C·m−2·d−1; October: 0.7 ± 0.05 mg C·m−2·d−1). Respiratory flux estimation by crustaceans (decapods and euphausiids) and fishes together was 6.86 mg C·m−2·d−1 during June, and 4.21 mg C·m−2·d−1 during October 2018, suggesting a functional role of this large micronektonic fauna in the biological carbon export in this region.3,26

Local energetic frustration conservation in protein families and superfamilies

Energetic local frustration offers a biophysical perspective to interpret the effects of sequence variability on protein families. Here we present a methodology to analyze local frustration patterns within protein families and superfamilies that allows us to uncover constraints related to stability and function, and identify differential frustration patterns in families with a common ancestry. We analyze these signals in very well studied protein families such as PDZ, SH3, ɑ and β globins and RAS families. Recent advances in protein structure prediction make it possible to analyze a vast majority of the protein space. An automatic and unsupervised proteome-wide analysis on the SARS-CoV-2 virus demonstrates the potential of our approach to enhance our understanding of the natural phenotypic diversity of protein families beyond single protein instances. We apply our method to modify biophysical properties of natural proteins based on their family properties, as well as perform unsupervised analysis of large datasets to shed light on the physicochemical signatures of poorly characterized proteins such as the ones belonging to emergent pathogens.RGP thanks Professor Christine Orengo and Nicola Bordin for early discussions and data provision. RGP holds a fellowship from Grant IHMC22/00007 funded by the Instituto de Salud Carlos III (ISCIII) and by the European Union NextGenerationEU/PRTR. C.P. is supported by the fellowship “Juan de La Cierva - Formación” from the Spanish Ministry of Education and Science (ref. FJC2021-046655-I). DUF and MIF are supported by the Consejo de Investigaciones Cientificas y Tecnicas (CONICET). PGW is supported by the Center for Theoretical Biological Physics sponsored by the NSF grant PHY-2019745 and the D.R. Bullard-Welch Chair at the Rice University Grant C-0016.Peer ReviewedPostprint (published version

Olaparib in combination with pegylated liposomal doxorubicin for platinum-resistant ovarian cancer regardless of BRCA status : a GEICO phase II trial (ROLANDO study)

There is limited evidence for the benefit of olaparib in platinum-resistant ovarian cancer (PROC) patients with BRCA wild-type tumors. This study investigated whether this combination of a DNA-damaging chemotherapy plus olaparib is effective in PROC regardless BRCA status. Patients with high-grade serous or endometrioid ovarian carcinoma and one previous PROC recurrence were enrolled regardless of BRCA status. Patients with ≤4 previous lines (up to 5 in BRCA -mut) with at least one previous platinum-sensitive relapse were included; primary PROC was allowed only in case of BRCA -mut. Patients initially received six cycles of olaparib 300 mg b.i.d. (biduum) + intravenous pegylated liposomal doxorubicin (PLD) 40 mg/m 2 (PLD40) every 28 days, followed by maintenance with olaparib 300 mg b.i.d. until progression or toxicity. The PLD dose was reduced to 30 mg/m 2 (PLD30) due to toxicity. The primary endpoint was progression-free survival (PFS) at 6 months (6m-PFS) by RECIST version 1.1. A proportion of 40% 6m-PFS or more was considered of clinical interest. From 2017 to 2020, 31 PROC patients were included. BRCA mutations were present in 16%. The median of previous lines was 2 (range 1-5). The overall disease control rate was 77% (partial response rate of 29% and stable disease rate of 48%). After a median follow-up of 10 months, the 6m-PFS and median PFS were 47% and 5.8 months, respectively. Grade ≥3 treatment-related adverse events occurred in 74% of patients, with neutropenia/anemia being the most frequent. With PLD30 serious AEs were less frequent than with PLD40 (21% versus 47%, respectively); moreover, PLD30 was associated with less PLD delays (32% versus 38%) and reductions (16% versus 22%). The PLD-olaparib combination has shown significant activity in PROC regardless of BRCA status. PLD at 30 mg/m 2 is better tolerated in the combination