Tutor profile: Charissa C.
Subject: Public Health
What is confounding? (Epidemiology 101)
X --> Y, where X is the cause and Y is the outcome. We are trying to determine if X actually causes Y. But in analysing the causative relationship, there are sometimes other factors like Z that simultaneously act on X and/or Y, which can confuse our analysis. For example, we want to do an experiment to determine if caffeine (X) cause insomnia (Y), but the people we recruit are human beings with lives outside the experiment (i.e. they aren't lab rats where you can literally control everything about them). So some humans recruited may have depression (Z), which can cause both insomnia and increased caffeine intake. Hence in order to accurately determine if X --> Y, we need to know what our Z(s) are.
Subject: Health and Medicine
What are the hallmarks of cancer?
1. Sustaining proliferative signalling receives signals to undergo cell proliferation— no regulation, no normal tissue homeostasis Increased Ligand, Receptor Expression cancer continuously secretes EGF (autocrine), IGF IGF secretion stimulates growth factor production (paracrine) EGF receptor— more signalling loss of negative regulators that inhibit proliferation of TGFß TGFß proliferate—> cell exit cell cycle: immunosuppressive functions dominate 2. Evading growth suppressors loss of function of tumour suppressors (p53, Rb)— typically protein expression will cause cell to pause in cycle and repair DNA before continuing mitosis loss of negative regulators that inhibit proliferation of TGFß overcome cell contact mediated inhibition of proliferation— typically when in contact with other cells, will stop growing to maintain tissue organisation 3. Resisting cell death loss of apoptosis loss of p53 tumour suppressor gene loss of pro-apoptotic regulators (Bax, Bad, Bim, Puma) gain of anti-apoptotic regulators (BCL2, BCL-XL) overcoming signals from ligand-activated death receptors 4. Inducing angiogenesis— forming of blood vessels tumours require waste removal and nutrients/oxygen for growth greater than 1-2mm tumours want to promote blood vessel formation— express pro-angiogenic factors (i.e. vascular Endothelial Growth Factor (VGEF), Fibroblast Growth Factor (FGF)); suppress anti-angiogenic factors (thrombospondin-1) angiogenic factors are unregulated by oncogene expression, a variety of growth factors and hypoxia 5. Enabling replicative immortality— avoid senescence a telomere is a region of repetitive nucleotides at each end of a chromosome that protects the chromosome end from deterioration or a fusion with neighbouring chromosomes as cells divide the telomeres shorten, when telomeres shorten to a critical length, cell undergoes replicative senescence BUT CANCER CELLS: express enzyme telomerase which regenerates telomeres, rendering cells resistant to replicative senescence 6. Activating invasion and metastasis— promotes tumour spread a multistep process involving local invasion, intravasation into blood/lymphatic vessels, extravation from vessel, growth in distant tissue site activation of EMT (epithelial to mesenchyme transition)— down regulates E-cadherin (mediates cell-cell contacts) increased expression/activation of proteins that promote cell invasion (matrix metalloproteinases (MMPs)), migration (Rac)
TO WHAT EXTENT IS IT POSSIBLE TO MAKE THE PUNISHMENT FIT THE CRIME?
The desire to punish wrongdoers measure for measure, hurt for hurt is universal. We all share a common abhorrence to the idea of suffering, doing what we can to avoid it and when hurt is inflicted upon us or to someone we feel connected to, we naturally want to exact punishment - cost for cost - on those who brought upon the suffering. But all our longing for a perfect exactment of justice, with every punishment befitting the crime, is for naught. The principle to be served may appear deceivingly simple: crimes deemed serious and repugnant by society deserve serious punishments and trivial offences merit only minor sanctions. But the perceived and actual fairness of our legal judgements are complicated by situa-tional nuances, our conflicting sympathies and ever-changing cultural tolerances. Save for a subset of clear-cut crimes where losses are easily quantifiable, I believe it is near impossible to make any punishment fit the crime in a way that pleases everyone.
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