Program for the 19th Annual John F. Sonnett Memorial Lecture Series: Legal Remedies Against the Council\u27s Failure to Act

Program for Legal Remedies Against the Council\u27s Failure to Act by Judge Ole Due, President of the European Court of Justice (1988-1994).https://ir.lawnet.fordham.edu/events_programs_sonnett_miscellaneous/1005/thumbnail.jp

John F. Sonnett Memorial Lecture Series: Legal Remedies Against the Council\u27s Failure to Act

Lecture by President Ole Due of the European Court of Justice (1988-1994), regarding judicial activism in Europe and the United States. Includes biography and speaker introduction.https://ir.lawnet.fordham.edu/events_programs_sonnet_lectures/1004/thumbnail.jp

Circulating markers of extracellular matrix remodelling in severe COVID-19 patients

Background Abnormal remodelling of the extracellular matrix (ECM) has generally been linked to pulmonary inflammation and fibrosis and may also play a role in the pathogenesis of severe COVID-19. To further elucidate the role of ECM remodelling and excessive fibrogenesis in severe COVID-19, we examined circulating levels of mediators involved in various aspects of these processes in COVID-19 patients. Methods Serial blood samples were obtained from two cohorts of hospitalised COVID-19 patients (n = 414). Circulating levels of ECM remodelling mediators were quantified by enzyme immunoassays in samples collected during hospitalisation and at 3-month follow-up. Samples were related to disease severity (respiratory failure and/or treatment at the intensive care unit), 60-day total mortality and pulmonary pathology after 3-months. We also evaluated the direct effect of inactivated SARS-CoV-2 on the release of the different ECM mediators in relevant cell lines. Results Several of the measured markers were associated with adverse outcomes, notably osteopontin (OPN), S100 calcium-binding protein A12 and YKL-40 were associated with disease severity and mortality. High levels of ECM mediators during hospitalisation were associated with computed tomography thorax pathology after 3-months. Some markers (i.e. growth differential factor 15, galectin 3 and matrix metalloproteinase 9) were released from various relevant cell lines (i.e. macrophages and lung cell lines) in vitro after exposure to inactivated SARS-CoV-2 suggesting a direct link between these mediators and the causal agent of COVID-19. Conclusion Our findings highlight changes to ECM remodelling and particularly a possible role of OPN, S100A12 and YKL-40 in the pathogenesis of severe COVID-19

Integrative clustering reveals a novel split in the luminal A subtype of breast cancer with impact on outcome

Background: Breast cancer is a heterogeneous disease at the clinical and molecular level. In this study we integrate classifications extracted from five different molecular levels in order to identify integrated subtypes. Methods: Tumor tissue from 425 patients with primary breast cancer from the Oslo2 study was cut and blended, and divided into fractions for DNA, RNA and protein isolation and metabolomics, allowing the acquisition of representative and comparable molecular data. Patients were stratified into groups based on their tumor characteristics from five different molecular levels, using various clustering methods. Finally, all previously identified and newly determined subgroups were combined in a multilevel classification using a "cluster-of-clusters" approach with consensus clustering. Results: Based on DNA copy number data, tumors were categorized into three groups according to the complex arm aberration index. mRNA expression profiles divided tumors into five molecular subgroups according to PAM50 subtyping, and clustering based on microRNA expression revealed four subgroups. Reverse-phase protein array data divided tumors into five subgroups. Hierarchical clustering of tumor metabolic profiles revealed three clusters. Combining DNA copy number and mRNA expression classified tumors into seven clusters based on pathway activity levels, and tumors were classified into ten subtypes using integrative clustering. The final consensus clustering that incorporated all aforementioned subtypes revealed six major groups. Five corresponded well with the mRNA subtypes, while a sixth group resulted from a split of the luminal A subtype; these tumors belonged to distinct microRNA clusters. Gain-of-function studies using MCF-7 cells showed that microRNAs differentially expressed between the luminal A clusters were important for cancer cell survival. These microRNAs were used to validate the split in luminal A tumors in four independent breast cancer cohorts. In two cohorts the microRNAs divided tumors into subgroups with significantly different outcomes, and in another a trend was observed. Conclusions: The six integrated subtypes identified confirm the heterogeneity of breast cancer and show that finer subdivisions of subtypes are evident. Increasing knowledge of the heterogeneity of the luminal A subtype may add pivotal information to guide therapeutic choices, evidently bringing us closer to improved treatment for this largest subgroup of breast cancer.Peer reviewe

Respiratory dysfunction three months after severe COVID-19 is associated with gut microbiota alterations

Background: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory infection, mounting evidence suggests that the gastrointestinal (GI) tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and are related to long-term respiratory dysfunction remains unknown. Methods: Plasma was collected during hospital admission and after three months from the NOR-Solidarity trial (n = 181) and analysed for markers of gut barrier dysfunction and inflammation. At the three-month follow-up, pulmonary function was assessed by measuring the diffusing capacity of the lungs for carbon monoxide (DLCO ). Rectal swabs for gut microbiota analyses were collected (n = 97) and analysed by sequencing the 16S rRNA gene. Results: Gut microbiota diversity was reduced in COVID-19 patients with respiratory dysfunction, defined as DLCO below the lower limit of normal three months after hospitalisation. These patients also had an altered global gut microbiota composition, with reduced relative abundance of 20 bacterial taxa and increased abundance of five taxa, including Veillonella, potentially linked to fibrosis. During hospitalisation, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO2 /fiO2 -(P/F ratio)Respiratory dysfunction three months after severe COVID-19 is associated with gut microbiota alterationsacceptedVersio

Penggunaan Media Gambar Dalam Meningkatkan Kemampuan Membaca Permulaan Siswa Kelas I SDN Uwedaka Kecamatan Pagimana Kabupaten Banggai

Pokok permasalahan dalam penelitian ini adalah rendahnya tingkat kemampuan membaca permulaan siswa kelas I SDN Uwedaka dalam pembelajaran Bahasa Indonesia. Tujuan Penelitian adalah untuk meningkatkan kemampuan membaca permulaan siswa kelas I SDN Uwedaka Kecamatan Pagimana Kabupaten Banggai. Berdasarkan hasil observasi yang didapatkan masih terdapat beberapa siswa yang sama sekali belum bisa membaca. Pembelajaran membaca permulaan di SDN Uwedaka selama ini hanya menggunakan media pembelajaran yang konvensional yaitu dengan menggunakan papan tulis, pembelajaran yang hanya berpusat pada guru, penggunaan media dalam pembelajaran sebagai alat bantu masih sangat terbatas, hal ini menyebabkan kemampuan membaca permulaan yang masih rendah dan terlihat hampir 65% siswa masih mengalami kesulitan membaca dalam proses belajar mengajar. Metode yang digunakan adalah metode deskriptif kualitatif dan kuantitatif. Data kualitatif didapatkan dari hasil tes dan observasi siswa dan guru. data kuantitatif didapatkan dari hasil tes belajar. Desain penelitian ini mengacu pada desain oleh Kemmis dan Mc Taggart yang terdiri dari empat tahapan, yaitu perencanaan, pelaksanaan tindakan, observasi dan refleksi. Data dikumpulkan melalui penilaian proses dan penilaian hasil setiap akhir tindakan. Penelitian ini dilakukan dalam dua siklus. Pada siklus I diperoleh nilai rata-rata siswa yaitu sebesar 67 dengan ketuntasan belajar klasikal sebesar 40% serta daya serap 66,6%. Pada siklus II, nilai rata-rata meningkat menjadi 83 dengan ketuntasan klasikal sebesar 100% serta daya serap klasikal sebesar 83,3%. Bersarkan hasil penelitian maka dapat disimpulkan bahwa penggunaan media gambar dapat meningkatkan kemampuan membaca permulaan terhadap siswa kelas I SDN Uwedaka Kecamatan Pagimana Kabupaten Banggai