170 research outputs found

    The Role of Liberal Arts Education on Academic Choices: The American University in Cairo Case Study

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    Providing a qualified higher education is a crucial component of any developmental plan in any country. This paper tackles the issue of educational decisions and will mainly focus on presenting the American University in Cairo (AUC) as a case study. The paper addresses undergraduate college students’ choices of their subjects and fields of study during the first year of university and how liberal arts education influence such decisions. The main aim is to build valuable recommendations to ease the transition of students from high school to universities, help them rationally choose their area of study, facilitate the financial burden on students and their families, eliminate discrimination among students, and highlight the importance of inclusivity of various types of students in the academic institutions to have well-rounded candidates who serve the developmental plans of their country. The research proves the close relationship between the previously mentioned factors and students’ academic decisions. Using the liberal arts concepts while updating curriculums and policies may benefit students. Realize career plans and have compatible jobs. Assessing and improving the relevance of the Egyptian higher education system could be one of the leading forces behind the country’s development and growth

    Leukoerythroblastosis with Cytopenia as an Initial Presentation of Lung Adenocarcinoma

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    A 74-year-old male with a history of chronic lymphocytic leukemia (CLL) previously treated with fludarabine/cyclophosphamide/rituximab (FCR) 5 years ago, presented with progressive fatigue, mucocutaneous bleeding, and cytopenias (hemoglobin 51 g/L, platelets 8.0 × 109/L, lymphocytes 0.4 × 109/L). He had normal respiratory findings, and no lymphadenopathy or hepatosplenomegaly. Further workup revealed a small spiculated lung nodule and multiple sclerotic bony lesions. Due to bleeding/profound thrombocytopenia, lung biopsy was not feasible. Peripheral smear revealed leukoerythroblastosis with few nucleated red blood cells and left shift of granulocytes. Bone marrow (BM) aspirate yielded a dry tap with clusters of extrinsic atypical cells on touch preparations. BM core biopsy showed infiltration and near complete replacement by a population of highly atypical cells with surrounding fibrosis. Cells were positive for cytokeratins CK7 and CK8/18, Napsin A, and thyroid transcription factor-1, specific for a primary poorly differentiated lung adenocarcinoma. Leukoerythroblastosis in association with cytopenia often indicates a BM infiltration and warrants an early BM biopsy to rule out hematological and solid malignancies, particularly in CLL patients treated with FCR. In our case, a diagnosis of a lung adenocarcinoma was established by BM examination, the only clinically feasible diagnostic modality

    Molecular heterogeneity of non-small cell lung carcinoma patient-derived xenografts closely reflect their primary tumors

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    Availability of lung cancer models that closely mimic human tumors remains a significant gap in cancer research, as tumor cell lines and mouse models may not recapitulate the spectrum of lung cancer heterogeneity seen in patients. We aimed to establish a patient-derived tumor xenograft (PDX) resource from surgically resected non-small cell lung cancer (NSCLC). Fresh tumor tissue from surgical resection was implanted and grown in the subcutaneous pocket of non-obese severe combined immune deficient (NOD SCID) gamma mice. Subsequent passages were in NOD SCID mice. A subset of matched patient and PDX tumors and non-neoplastic lung tissues were profiled by whole exome sequencing, single nucleotide polymorphism (SNP) and methylation arrays, and phosphotyrosine (pY)-proteome by mass spectrometry. The data were compared to published NSCLC datasets of NSCLC primary and cell lines. 127 stable PDXs were established from 441 lung carcinomas representing all major histological subtypes: 52 adenocarcinomas, 62 squamous cell carcinomas, one adeno-squamous carcinoma, five sarcomatoid carcinomas, five large cell neuroendocrine carcinomas, and two small cell lung cancers. Somatic mutations, gene copy number and expression profiles, and pY-proteome landscape of 36 PDXs showed greater similarity with patient tumors than with established cell lines. Novel somatic mutations on cancer associated genes were identified but only in PDXs, likely due to selective clonal growth in the PDXs that allows detection of these low allelic frequency mutations. The results provide the strongest evidence yet that PDXs established from lung cancers closely mimic the characteristics of patient primary tumors

    Targeting targeted agents: open issues for clinical trial design

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    Molecularly targeted agents for the treatment of solid tumors had entered the market in the last 5 years, with a great impact upon both the scientific community and the society. Many randomized phase III trials conducted in recent years with new targeted agents, despite previous data coming from preclinical research and from phase II trials were often promising, have produced disappointingly negative results. Some other trials have actually met their primary endpoint, demonstrating a statistically significant result favouring the experimental treatment. Unfortunately, with a few relevant exceptions, this advantage is often small, if not negligible, in absolute terms. The difference between statistical significance and clinical relevance should always be considered when translating clinical trials' results in the practice. The reason why this 'revolution' did not significantly impact on cancer treatment to displace chemotherapy from the patient' bedside is in part due to complicated, and in many cases, unknown, mechanisms of action of such drugs; indeed, the traditional way the clinical investigators were used to test the efficacy of 'older' chemotherapeutics, has become 'out of date' from the methodological perspective. As these drugs should be theoretically tailored upon featured bio-markers expressed by the patients, the clinical trial design should follow new rules based upon stronger hypotheses than those developed so far. Indeed, the early phases of basic and clinical drug development are crucial in the correct process which is able to correctly identify the target (when present). Targeted trial designs can result in easier studies, with less, better selected, and supported by stronger proofs of response evidences, patients, in order to not waste time and resources

    Biallelic variants in SLC38A3 encoding a glutamine transporter cause epileptic encephalopathy

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    The solute carrier (SLC) superfamily encompasses >400 transmembrane transporters involved in the exchange of amino acids, nutrients, ions, metals, neurotransmitters and metabolites across biological membranes. SLCs are highly expressed in the mammalian brain; defects in nearly 100 unique SLC-encoding genes (OMIM: https://www.omim.org) are associated with rare Mendelian disorders including developmental and epileptic encephalopathy (DEE) and severe neurodevelopmental disorders (NDDs). Exome sequencing and family-based rare variant analyses on a cohort with NDD identified two siblings with DEE and a shared deleterious homozygous splicing variant in SLC38A3. The gene encodes SNAT3, a sodium-coupled neutral amino acid transporter and a principal transporter of the amino acids asparagine, histidine, and glutamine, the latter being the precursor for the neurotransmitters GABA and glutamate. Additional subjects with a similar DEE phenotype and biallelic predicted-damaging SLC38A3 variants were ascertained through GeneMatcher and collaborations with research and clinical molecular diagnostic laboratories. Untargeted metabolomic analysis was performed to identify novel metabolic biomarkers. Ten individuals from seven unrelated families from six different countries with deleterious biallelic variants in SLC38A3 were identified. Global developmental delay, intellectual disability, hypotonia, and absent speech were common features while microcephaly, epilepsy, and visual impairment were present in the majority. Epilepsy was drug-resistant in half. Metabolomic analysis revealed perturbations of glutamate, histidine, and nitrogen metabolism in plasma, urine, and cerebrospinal fluid of selected subjects, potentially representing biomarkers of disease. Our data support the contention that SLC38A3 is a novel disease gene for DEE and illuminate the likely pathophysiology of the disease as perturbations in glutamine homeostasis

    Patients' preferences for subcutaneous trastuzumab versus conventional intravenous infusion for the adjuvant treatment of HER2-positive early breast cancer: final analysis of 488 patients in the international, randomized, two-cohort PrefHer study

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    PrefHer revealed compelling and consistent patient preference for subcutaneous (s.c.) trastuzumab, regardless of delivery by single-use injection device or hand-held syringe. s.c. trastuzumab was well-tolerated and safety data, including immunogenicity, were consistent with previous reports. No new safety signals were identified compared with the known intravenous trastuzumab profile in early breast cance

    A review of perspectives on the use of randomization in phase II oncology trials

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    Historically, phase II oncology trials assessed a treatment’s efficacy by examining its tumor response rate in a single-arm trial. Then, approximately 25 years ago, certain statistical and pharmacological considerations ignited a debate around whether randomized designs should be utilized instead. Here, based upon an extensive literature review, we review the arguments on either side of this debate. In particular, we describe the numerous factors that relate to the reliance of single-arm trials on historical control data, and detail the trial scenarios in which there was general agreement on preferential utilization of single-arm or randomized design frameworks, such as the use of single-arm designs when investigating treatments for rare cancers. We then summarize the latest figures on phase II oncology trial design, contrasting current design choices against historical recommendations on best practice. Ultimately, we find several ways in which the design of recently completed phase II trials does not appear to align with said recommendations. For example, despite advice to the contrary, only 66.2% of the assessed trials that employed progression-free survival as a primary or co-primary outcome used a randomized comparative design. In addition, we identify that just 28.2% of the considered randomized comparative trials came to a positive conclusion, as opposed to 72.7% of the single-arm trials. We conclude by describing a selection of important issues influencing contemporary design, framing this discourse in light of current trends in phase II, such as the increased use of biomarkers and recent interest in novel adaptive designs

    Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

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    Contains fulltext : 172380.pdf (publisher's version ) (Open Access
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