Search

The Agulhas leakage is an important contributor to the global thermohaline conveyor system, adding warm and saline subtropical waters from the Indian Ocean to the South-east Atlantic Ocean. It has been proposed that weaker Agulhas leakage occurred during glacial stages, but that leakage was reinvigorated during deglaciations and was, in turn, potentially important for the development of interglacial warmth.Little is known about the longer-term evolution of Agulhas leakage during the Pliocene and Pleistocene (the last 5.3 Ma). In the Pliocene, the continental ice sheets were smaller in size, and the position and strength of key ocean and atmosphere circulation systems in the South Atlantic region were different. The Pliocene is also characterised by a series of gateway changes which are argued to have affected North Atlantic climate, but the response of the Agulhas leakage system remains unclear. It is also unclear whether the ‘early deglaciation’ signal is a specific component of the late Pleistocene 100 kyr cycles. Identifying how and when this signal developed could have important implications for understanding the impact of ocean circulation changes on the development of the mid-Pleistocene climate transition (MPT) ~1.2-0.6 Ma, when the period of the glacial-interglacial cycles shifted from ~41 kyr to ~100 kyr.Here we present initial results from a new Cape Basin site (Site U1479, 35°03.53′S; 17°24.06′E), which was recovered by IODP Expedition 361 in 2016 from the western slope of the Agulhas Bank (Hall et al., 2016). We combine reconstructions of sea surface temperatures (using the alkenone-derived UK37’ index) and sea surface salinity (from alkenone dD analysis) with details of planktonic foraminifera assemblages, to identify and understand variability in Agulhas leakage operating across both orbital and longer timescales. There is an overall cooling of ~4°C since the Pliocene, but it is focussed around ~2 Ma and from 1.2 Ma. Orbital scale and longer-term variability in SST, sea surface salinity and Agulhas leakage fauna are also determined, demonstrating that the Agulhas leakage system has evolved across a range of timescales through the Plio-Pleistocene, especially in association with the MPT.ReferencesHall, I.R., Hemming, S.R., LeVay, L.J., and the Expedition 361 Scientists, 2016. Expedition 361 Preliminary Report: South African Climates (Agulhas LGM Density Profile). International Ocean Discovery Program. http://dx.doi.org/10.14379/iodp.pr.361.2

Mutational analysis of SARS-CoV-2 can quantify their relative importance over time, enable the dominant mutations to be identified and facilitate near real-time detection, comparison, and tracking of evolving variants. Collected samples in Asturias an autonomous community of Spain with a large aged population, and high levels of migration and tourism was monitored and tracked from its beginning in February 2020 until its decline and stabilization in August 2021, were characterized using whole genomic sequence and single nucleotide polymorphism. Data held in the GISAID database was analyzed to establish patterns in the appearance and persistence of SARS-CoV-2 strains. Only 138 non-synonymous mutations occurring in more than 1% of the population of SARS-CoV-2 were found, identifying 10 major variants worldwide (7 arose before January 2021), 19 regional and 1 local. In Asturias only 17 different variants were found. After vaccination, no further regional majority variants were found. Only half of the defined variants circulated and no new variants were generated, indicating that infection control measures (fast diagnosis, prevention measures and vaccination) were efficient.

Objective: Compare the effectiveness and safety of the ECV when the procedure is performed by senior experienced obstetricians or by super-specialized professionals who composed a dedicated team. Design: Longitudinal prospective analysis. Setting: 1st of January of 2018 and 31st of December of 2019. Population: Pregnant women with non-cephalic presentation and no contraindication for vaginal delivery. Methods: Longitudinal prospective analysis of ECV performed in a tertiary hospital. From 1/1st/2018 to 10/1st/2019, ECV were performed by two senior experienced obstetricians who composed the dedicated team for ECV, designed as Group A. From 10/1st/2019 to 12/31st/2019, ECV was performed by two seniors obstetricians, designed as Group B. Ritodrine was administered during 30 minutes just before the procedure. Propofol was used for sedation. Main Outcome Measures: ECV success rate, ECV complication rate, cesarean section 24 h after ECV. Results: 186 pregnant women were recruited (150 patients in group A and 36 patients in group B). ECV success rate increased from 47.2% (31.7-63.2) in Group B to 74.0% (66.6-80.5) in Group A. The greatest increase in the success rate of ECV was seen in nulliparae, from 38.5% (21.8-57.6) in group B to 69.1% (59.4-77.6). Complications rate decreased from 22.2% (11.1-37.6) in Group B to 9.3% (5.5-14.8) in Group A. Conclusions: The introduction of an experienced dedicated team improves ECV success rate, especially in primiparas, and it also reduces ECV complications rate. Funding: The authors received no financial support for the research, authorship, and/or publication of this article. Keywords: Sedation, Experience, ECV, Breech presentation

BACKGROUND Fetal smallness affects 10% of pregnancies. These fetuses are at a higher risk of adverse outcomes. Their management using estimated fetal weight (EFW) and feto-maternal Doppler has a high sensitivity for adverse outcomes; however, more than 60% of fetuses are electively delivered at 37-38 weeks. On the other hand, the classification using angiogenic factors (AF) seems to have a lower false positive rate. Here we present a protocol for the GRAFD trial, which compares the management of small fetuses at term using AF or Doppler. OBJECTIVE The primary objective is to demonstrate that classification based on AF is not inferior to EFW and Doppler to detect fetuses at risk of adverse perinatal outcomes. METHODS This is a multicentre, open-label, randomized controlled trial conducted in 20 hospitals across Spain. A total of 1,030 singleton pregnancies with an EFW ≤10th percentile at 36+0 to 37+6 weeks will be recruited and randomly allocated to either the control or the intervention group. In the control group, standard Doppler-based management will be used. In the intervention group, cases with a soluble fms-like tyrosine kinase to placental growth factor ratio (sFlt-1/PlGF) ≥38 will be classified as fetal growth restriction (FGR), otherwise as small for gestational age (SGA). In both arms, FGR will be delivered at ≥37 weeks and SGA at ≥40 weeks. We will assess the differences between groups calculating the relative risks (RR) and their 95% confidence intervals. RESULTS The study is in the recruitment and data collection phase. The study results are expected to be published in peer-reviewed journals and disseminated at international conferences by the end of 2022 or in early 2023. CONCLUSIONS The AF-based protocol may reduce the number of pregnancies with classified as FGR without worsening perinatal outcomes. Moreover, reducing the number of unnecessary labor inductions would reduce costs and the risks derived from possible iatrogenic complications. Additionally, fewer inductions would lower the rate of early-term neonates, thus improving neonatal outcomes and potentially reducing long-term infant morbidities. CLINICALTRIAL NCT04502823

Currently, the standard of care for luminal metastatic breast cancer is the combination of cyclin inhibitors with hormone therapy. Palbociclib and Ribociclib have been approved for marketing since 2017 and Abemaciclib since 2019 in Spain. In our center we have experience with the three cdk 4/6 inhibitors in different lines of treatment and patient profiles. We gather in the present work the unicentric experience with the three icdk 4/6. We have collected a total of 152 patients treated with the different cyclin inhibitors, achieving median PFS of 32.1 months for Palbociclib, 28.6 months for Ribociclib and 18.4 months for Abemaciclib. Overall survival data is still immature. The context of the patient and the disease has a significant impact on the results, as well as the line of treatment used. The toxicity profile of the three drugs does not differ from what the registry trials describe, with neutropenia being the most common side effect. We also describe dose reductions produced by the three icdk4/6. Conclusions: This is a real-life study with experience in a single center with the three icdk4/6 currently marketed with a cohort of more than 150 patients. We present data that conform to what was reported by the clinical trials PALOMA, MONALEESA and MONARCH. The data will be updated on the date of the congress for its presentation. Citation Format: Fernando Henao, Esteban Nogales Fernández, Lourdes Sevilla Ortega, Ruben De Toro Salas, Natalia Palazón Carrión, Maria del Carmen Álamo de la Gala, Alberto Sanchez-Camacho Mejías, Maria Luisa Sanchez Leon, Luis de la Cruz-Merino. Unicentric experience with icdk4/6 in metastatic breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-01-01.

e17598 Background: Rucaparib is a PARP inhibitor (PARPi) approved as maintenance therapy for platinum (Pt)-sensitive recurrent high-grade ovarian cancer (HGOC), and as treatment for BRCA-mutant HGOC patients. To date, there is little evidence about the efficacy and safety of rucaparib after prior exposure to PARPi. This subanalysis aims to describe the patients’ characteristics and treatment outcomes with rucaparib in women who were included in the rucaparib early access program (RAP) in Spain and had received a prior PARPi. Methods: A retrospective study was conducted by GEICO at 22 hospitals in Spain to analyze data of 51 women treated within the RAP (600 mg BID). Adult women with HGOC, fallopian tube, or primary peritoneal cancer, who had received at least one prior PARPi before rucaparib were analyzed. Patients’ characteristics, medical history, safety, efficacy, and dosing data were collected. Results: A total of 14 women, with a median age of 63 years old (42-78) were included in this subanalysis. Of them, 92.9% were diagnosed of epithelial ovarian cancer and 78.6% had mutations in BRCA1/ 2 genes. The median number of lines before rucaparib was 5 (3-8), while the number of lines before the first PARPi was 3 (2-5). Except for one woman who had received 2 prior PARPis before rucaparib, the others had received just 1. Most patients were given olaparib as the first PARPi (n = 12, 85.8%), while niraparib was the initial PARPi in the remaining cases (n = 2, 14.3%). The outcomes of the treatment with rucaparib in these patients are outlined in table 1. Rucaparib was given as maintenance therapy in 1 patient and as treatment in 13 patients, 12 of them being Pt-resistant. The progression-free survival (PFS) ranged from 0.23 to 9.12 months. Adverse events (AE) of any grade were detected in 78.6% of patients, whereas AE of grade ≥3 affected 28.6% of women. Rucaparib dose was interrupted in 57.1% and reduced in 42.9% of patients. Only 1 patient discontinued rucaparib due to toxicity. No new safety signals were detected. Conclusions: This is one of the first real-word studies reporting the use of rucaparib after treatment with another PARPi. Even in these heavily pre-treated patients who had received prior PARPi, rucaparib efficacy has been notable in some cases, and its safety profile is consistent with that reported in previous clinical trials. Future studies should focus on the selection of patients who could benefit from rucaparib after prior PARPi exposure. [Table: see text]

e17562 Background: Rucaparib is a PARP inhibitor approved for the treatment of high-grade ovarian cancer (HGOC). Clinical trials have demonstrated its benefit both as maintenance therapy (MTN) for platinum (Pt)-sensitive recurrent HGOC, and as treatment (Tx) in BRCA-mutated relapsed or recurrent HGOC patients. Here we analyze real-world data from the rucaparib early access program (RAP) in Spain with focus in the long-term responder patients (LTR). Methods: A retrospective observational study was performed by GEICO at 22 hospitals in Spain that had treated patients within the RAP. Adult women with HGOC, fallopian tube, or primary peritoneal cancer were included and received rucaparib (600 mg BID) in the MTN, Tx Pt-sensitive or Tx Pt-resistant setting. Patients’ characteristics, medical history, safety, efficacy, and dosing data were collected. In this analysis, long-term response was defined as progression-free survival (PFS) ≥12 months for the MTN group and ≥6 months for the Tx group. LTR were stratified based on the rucaparib indication (MTN/Tx). Results: Between July 2020 and February 2021, 51 patients were recruited: 18 received rucaparib as MTN and 33 as Tx. In the MTN group, 6 patients (33.3%) were LTR, with a median age of 65 years (54-79). Of them, 2 patients (33.2%) harbored BRCA or RAD51C mutations. The median number of prior lines was 3 (2-6), being ≥5 in 33.2%, and 50.0% received prior bevacizumab. ECOG PS was ≤1 in all these patients, 66.6% had measurable disease and 50.0% achieved a partial response to prior Pt-based chemotherapy. In the Tx group, 10 patients (30.3%) were LTR, with a median age of 71 years (47-86). All of them harbored BRCA and/or RAD51C mutations. The median number of prior lines was 6 (2-9), with 60.0% receiving ≥5 prior lines, and 50.0% received prior bevacizumab. Regarding Pt-status, 40.0% of patients were Pt-sensitive and 60.0% were Pt-resistant. The ECOG PS was ≥1 in 30.0% of patients and 60.0% had measurable disease. The median PFS of LTR was not achieved in the MTN group and was 10.9 months (95% CI: 7.0-16.7) in the Tx group. Adverse events (AE) of any grade were reported in 66.6% of LTR within the MTN group and in 100.0% within the Tx group, while AE of grade ≥3 occurred in 16.6% and 50.0%, respectively. Rucaparib dose was reduced in 50.0% of LTR in the MTN group and 80.0% in the Tx group. Discontinuation rate due to rucaparib toxicity was 20.0% in the Tx group and there were no discontinuations due to toxicity in the MTN group. No new safety signals were detected. At present, 3 and 1 patients are still receiving rucaparib as MTN and Tx, respectively. Conclusions: A durable response was achieved in a notable proportion of patients, even despite their unfavorable conditions at treatment initiation (heavily pre-treated patients, partial response or resistance to Pt, or high volume of disease). The safety profile of rucaparib in this real-world setting is consistent with that reported in clinical trials.

Options for a negotiated financial settlement range among the most contentious issues raised by the withdrawal of the United Kingdom from the European Union. This article critically assesses the legal arguments underlying mutual financial claims. It then examines specific matters arising within the financial chapter of the bilateral negotiations, taking stock of the progress to date.

The silent spread of outsourcing in the processing of visa applications is a much under-researched phenomenon. Drawing on quantitative and qualitative data throughout the 2011–2015 period, this research offers empirical evidence of the oligopolistic structure of the Schengen visa processing market, exposing that European Union Member States rely extensively on non-EU transnational corporations. External service providers do not intervene in the qualitative assessment of the applicant, yet they dominate all the remaining stages of the visa process, thus affecting temporary migration. This study overcomes the facilitators-gatekeepers divide and contributes to a better understanding of the complex role visa processing companies play in the transnational network governance of migration.

Increasing bacterial resistance is strictly correlated to the increasing use of antibiotics, currently constituting a public health problem. The aim of this study was to describe the consumption of antibiotics in Asturias, an autonomous community in northwestern Spain, and compare the results obtained with data from elsewhere in Spain and other European countries. A descriptive study was carried out on the use of antibacterial drugs for systemic use, ATC code J01 in Asturias in 2011-2015. Data were obtained from the prescription-billing information system charged to the Health Service of Asturias. The consumption data are expressed in daily doses per 1,000 inhabitants and day (DHD), and number of packages per thousand inhabitants per day. The average weighted consumption of antibiotics for systemic use in the Asturian community was 26.23 daily doses per 1000 inhabitants per day (DHD) in 2015. This figure was higher than that of the EU/EEA population, which was 22.4 DHD, and that of the whole of Spain at 22.2 DHD. There is a wide variability in consumption among the different areas of the Asturian region. This variability is common to the rest of the country and Europe. It can be explained by the influence of the data used in the indicators and by the variability in medical practice. Priority should be given to homologating consumer-monitoring information systems and implementing national strategies aimed at providing more information to medical practitioners, encouraging the appropriate use of antibiotics so as to reduce variability, consumption and resistance.

Lawyers are important actors shaping the abortion debate in Mexico. Of 250 private and public sector criminal lawyers surveyed from four regions, the majority knew about abortion laws in their states. At least 80% agreed with abortion in cases of rape, risk to a woman's life or health, and fetal malformations. Overall, 61% agreed with the Mexico City law and 84% would defend a woman denied a legal abortion. In multivariate analysis, being very knowledgeable of abortion laws was a significant predictor of more "progressive" abortion opinions, support for the Mexico City law, and support for the health indication.

In opposition to Mexico City's legalization of first-trimester abortion, 17 Mexican states (53 percent) have introduced initiatives or reforms to ban abortion entirely, and other states have similar legislation pending. We conducted an opinion survey in eight states--four where constitutional amendments have already been approved and four with pending amendments. Using logistic regression analyses, we found that higher education, political party affiliation, and awareness of reforms/initiatives were significantly associated with support for the Mexico City law. Legal abortion was supported by a large proportion of respondents in cases of rape (45-70 percent), risk to a woman's life (55-71 percent), and risk to a woman's health (48-68 percent). A larger percentage of respondents favored the Mexico City law, which limits elective legal abortion to the first 12 weeks of gestation (32-54 percent), than elective abortion without regard to gestational limit (14-31 percent).

We report the MRI findings in a 3-week-old boy with D-transposition of the great arteries and an abnormal origin of the right subclavian artery from the pulmonary artery. This anomaly of the subclavian arteries is called isolation. It is infrequent in patients with a right aortic arch, but exceedingly rare in those with a left aortic arch. This is a unique report of the MRI findings in this congenital abnormality of the aortic arch.

The flow of patients between Primary Care (PC) and Specialized care (SC) is a common process. It carries many implications for the patient, physician and health system. In Urology, only benign prostatic hyperplasia (BPH) has referral criteria. Urinary incontinence, prostate cancer (PCa), and urological ultrasound, are in the process. The aim of this paper is to communicate, with critical analysis, the characteristics of the information recorded in the referral visit (clinical reasons / rationale) and the effectiveness for urology consultation.Observational, descriptive and quantitative study of the referral visits made between PC/SC (Urology) in the health care area of our hospital (December 2010-September 2012). We studied: Referral Visit Database (RVD), consultation document, HORUS system, and specific referral visit survey questionnaire. RESULTS. Referral visits account for 67.89% (all first consultations), 14.79% of the total number of visits. 78% were male (mean age 53 y.o). 11.84% recorded reason for consultation (98% in referral document) with normal priority (94.67%). 34% of them were for BPH. HORUS is not exploited for the referral visit. 40% start the diagnostic process with insufficient exams. 18.1% are listed as closed process / completed. Patient satisfaction was evaluated (20%). Key points in the improvement are: improve referral visit reason for consultations, to know patient's expectations, and to develop protocols (guidelines, and/or referral criteria). CONCLUSIONS. The referral process is complex. The computer system does not include the referral reason for consultation. Institutional agreement between PC/SC Urology must be reached to ensure uniformity in the implementation and support.

Background: Urinary incontinence (UI) is a major cause of morbidity in the world and is believed to affect up to 46% of the female population Our objective was to analyze the papers that describe stem-cell treatments for UI in women. Methods: We performed a systematic review of the literature from 1946 to date that reports on clinical trials that use stem cells to treat women with urinary incontinence. Results: Nine articles (7 observational and 2 randomized studies) met the inclusion criteria. No major adverse effects were observed in any of the studies. However, the efficacy results differ widely, as the methodology used for studies was very different, as described below. Conclusion: Stem-cell therapy is promising but still experimental, and further study is needed to identify certain factors. These facts include the ideal type of patient eligible for treatment (apparently those in whom intrinsic urethral dysfunction predominates), and to determine if treatment should be isolated or combined with other cells or procedures, which are the optimal doses and if it is a cost effective procedure.

We report the MRI findings in a 3-month-old boy with isolated left ventricular apical hypoplasia. This is a recently described congenital abnormality that consists of an odd, spherically shaped left ventricle due to absence of the ventricular apex. To our knowledge, isolated left ventricular apical hypoplasia has not been reported in a child.

MicroRNAs (miRNAs) are small, non-coding RNAs (18-25 nucleotides) that post-transcriptionally modulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs. In this context, the present study aimed to evaluate the in vitro effects of miR-153 inhibition in the breast carcinoma cell line MDA-MB-231. Forty-eight hours after MDA-MB-231 cells were transfected with the miR-153 inhibitor, an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was utilized to determine the effects of miR-153 on cell viability. Flow cytometry analysis and assessment of caspase 3/7 activity were adopted to determine whether miR-153 affects the proliferation rates and apoptosis levels of MDA-MB-231 cells. Our results showed that silencing of miR-153 significantly inhibited growth when compared to controls at 48 hours, reducing proliferation by 37.6%, and inducing apoptosis. Further studies are necessary to corroborate our findings and examine the potential use of this microRNA in future diagnostic and therapeutic interventions.