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1
Chen, Ming-Jen. Combination gene therapy for colorectal cancer. University of Birmingham, 2003.
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2
(Introduction), Vladimir Kramnik, ed. Chess Gems: 1,000 Combinations You Should Know. Mongoose Press, 2007.
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3
Slack, Jonathan. 3. Mutations and gene variants. Oxford University Press, 2014. http://dx.doi.org/10.1093/actrade/9780199676507.003.0003.
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All gene variants originate as mutations. Most variants in the genome of any given individual are not new mutations but have been inherited from previous generations. ‘Mutations and gene variants’ shows that mutations can occur in any cell of the body, but in order to be inherited they must occur in the DNA of the reproductive cells. There are numerous genetic diseases caused by a single mutation in one gene, and the examples considered here are cystic fibrosis, haemophilia, achondroplasia, and Holt-Oram Syndrome. In such cases, the inheritance of the abnormal gene variant follows simple Mendelian rules. The origin of cancer is explained as a combination of mutations occurring in a single cell of the body. Inherited gene variants predisposing to cancer do so because they reduce the number of new mutations required.
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Perkins, Elizabeth C., Shaun P. Brothers, and Charles B. Nemeroff. Animal Models for Post-Traumatic Stress Disorder. Edited by Charles B. Nemeroff and Charles R. Marmar. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190259440.003.0024.
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Animal models of post-traumatic stress disorder (PTSD) provide a wellspring of biological information about this complex condition by providing the opportunity to manipulate trauma exposure and measure biological outcomes in a systematic manner that is not possible in clinical studies. Symptoms of PTSD may be induced in animals by physical (immobilization, foot shock, underwater stress) and psychological stressors (exposure to predator, social defeat, early life trauma) or a combination of both. In addition, genetic, epigenetic and transgenic models have been created by breeding animals with a behavioral propensity for maladaptive stress response or by directly manipulating genes that have been implicated in PTSD. The effect of stressors in animals is measured by a variety of means, including observation of behavior, measurement of structural alterations in the brain and of physiological markers such as HPA axis activity and altered gene expression of central nervous system neurotransmitter system components including receptors. By comparing changes observed in stress exposed animals to humans with PTSD and by comparing animal response to treatments that are effective in humans, we can determine the validity of PTSD animal models. The identification of a reliable physiological marker of maladaptive stress response in animals as well as standard use of behavioral cutoff criteria are critical to the development of a valid animal model of PTSD.
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Holland, John H. 5. Specialization and diversity. Oxford University Press, 2014. http://dx.doi.org/10.1093/actrade/9780199662548.003.0005.
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A multi-celled organism consists of specialized cells organized into a variety of communities. ‘Specialization and diversity’ shows that community-based organization extends both downward and upward from the level of organisms, giving rise to the hierarchies that characterize complex adaptive systems. Diverse specialist agents attend to, and process, selected signals. The diversity is sustained by a combination of boundaries, signals, and signal-processing. A characteristic of this signal-processing is that relatively small parts of signals—tags—route the signals through the boundaries. This tag-based control allows cells to exist in a diverse range of conditions by activating only genes that are relevant to the current situation.
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Banerjee, Amitava, and Kaleab Asrress. Risk factors for cardiovascular disease. Edited by Patrick Davey and David Sprigings. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199568741.003.0086.
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The most prevalent cardiovascular diseases (CVDs) are atherosclerotic, affecting all arterial territories. Epidemiologic studies such as the Framingham and INTERHEART studies have firmly established the commonest or ‘traditional’ risk factors for CVD; namely, smoking, hypertension, diabetes mellitus, hypercholesterolaemia, and a family history of CVD. The ‘risk-factors approach’ to CVD looks at these factors, individually and in combination, in the causation of disease. The complex causation pathways involve interplay of individual factors, whether genetic or environmental. More recently, there has been increasing interest in ‘epigenetics’ or the way in which the environment interacts with genes in the process underlying CVD. This chapter presents an analysis of the traditional and novel risk factors for CVD.
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Buchman, Andrew. Singin’ in the Rain. Oxford University PressNew York, NY, 2024. http://dx.doi.org/10.1093/9780197760062.001.0001.
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Abstract This new film guide from Oxford traces the film’s genesis, analyzes the music and dance that make Singin’ in the Rain Gene Kelly’s best-known work, and examines some of the modern scholarship and new artworks the film has inspired. Singin’ combines a streamlined 1920s storyline with vivid characters, memorable wisecracks and comedy, romance, riveting dancing, memorable music, gorgeous sets, props, and costumes, and virtuosic camera work. But this supposedly simple, safe modern fairy tale is not simplistic. It is a social satire with a point of view on human nature and morality—what screenwriter Betty Comden called “a deep thread of real feeling.” The continuing success of Singin’ in the Rain is based on a contrasting but palatable combination of Comden and co-writer Adolph Green’s biting and irreverent satire (a residue from their Revuer days) and co-directors Gene Kelly and Stanley Donen’s superbly musicalized and deeply nostalgic Hollywood history lessons. Script drafts, production reports, and other sources reveal how commercially appealing romantic nostalgia, bolstered in the conservative climate created by the Cold War and blacklists of workers deemed politically suspect, largely effaced the progressive political views, forged in the late 1930s, of the film’s creators.
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Fenno, Lief E., and Karl Deisseroth. Optogenetics and Related Technologies for Psychiatric Disease Research. Edited by Dennis S. Charney, Eric J. Nestler, Pamela Sklar, and Joseph D. Buxbaum. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190681425.003.0006.
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Studying intact systems with simultaneous local precision and global scope is a fundamental challenge in biology. This familiar trade-off leads to important conceptual and experimental difficulties in psychiatric disease research and throughout the study of complex biological systems. Part of a solution may arise from optogenetics: the combination of genetic and optical methods to achieve gain- or loss-of-function of temporally defined events in specific cells embedded within intact living tissue or organisms. Such precise causal control within the functioning intact system can be achieved via introduction of genes that confer to cells both light-detection capability and specific effector function. A broad array of optogenetic tools and neuroscience applications have driven the wide adoption of optogenetics as a standard approach in neuroscience.
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Zoysa, Aruni De. Other bacterial diseasesDiseases caused by corynebacteria and related organisms. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780198570028.003.0019.
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The genus Corynebacterium contains the species Corynebacterium diphtheriae and the non-diphtherial corynebacteria. C. diphtheriae is the major human pathogen in this genus, but several species of nondiphtheria corynebacteria appear to be emerging as important pathogens.Zoonotic corynebacteria rarely cause disease in humans, but recent reports have indicated that the frequency and severity of infection associated with Corynebacterium ulcerans has increased in many countries. In the past most human C.ulcerans infections have occurred through close contact with farm animals or by consumption of unpasteurised dairy products. However, recently, there have been cases of human infection following close contact with household pets. Rhodococcus equi appears to be emerging as an important pathogen in immunocompromised patients, especially those with acquired immunodeficiency syndrome (AIDS). Human infections caused by Corynebacterium pseudotuberculosis is still a very rare occurrence.Antibiotics in combination with surgery and vaccination are the treatment of choice for human infection. Control of human infection is best achieved by raising awareness in those at risk (e.g. domestic pet owners, sheep shearers, the immunocompromised), clinicians involved in treating these groups and by vaccination. Reducing prevalence in the animal population could be achieved by improving hygiene in farms and husbandry practices, reducing minor injuries (e.g. cuts and abrasions) during routine procedures, and by vaccination.
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Dixon, Bradley P., J. Christopher Kingswood, and John J. Bissler. Tuberous sclerosis complex renal disease. Edited by Neil Turner. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0330.
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Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder affecting almost all organs. It has wider phenotypic variation than often appreciated, with less than half showing the combination of characteristic facial angiofibromas, epilepsy, and mental retardation. Renal angiomyolipomata or cysts are found in 90% and renal failure was historically a common mode of adult death from the disease. Pulmonary lymphangioleiomyomatosis is restricted to females. Angiomyolipomata or cystic disease, or both, may cause renal failure. Angiomyolipomata may also haemorrhage, especially from larger lesions. Manifestations of brain involvement substantially complicate management of many patients with TSC. The causative genes TSC1 and TSC2 encode tuberin and hamartin which are involved in control of the mammalian target of rapamycin pathway. Inhibitors of that pathway, such as sirolimus and everolimus, are therefore logical approaches to therapy and have been shown to be effective in reducing angiomyolipomata volume. It remains to be seen whether they can protect renal function.
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Canli, Turhan. Neurogenethics. Edited by Turhan Canli. Oxford University Press, 2014. http://dx.doi.org/10.1093/oxfordhb/9780199753888.013.27.
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Ethical inquiry has followed advances in biology for decades, and different fields within biology have given rise to overlapping yet distinct areas of ethical inquiry. Genethics focuses on the ethics of genetics. Neuroethics focuses on the ethics of neuroscience. The author suggests that developments in molecular psychology, in which the tools of molecular biology are applied to study behavior, bring a new confluence of factors to generate a set of new questions, unique to the combination of neuroscience and genetics: neurogenethics—the ethics of neurogenetics. The questions are unique and novel because they emerge when genetic techniques are applied to the brain: to reprogram neural circuits and psychological processes, better predict behavior, personalize mental health treatment, and understand the Self. This chapter outlines the problem space and discusses specific examples of future neurogenethics research areas: viral-mediated gene therapy directed at the brain, optogenetics, imaging genetics, therapygenetics, and direct-to-consumer genomics.
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Walsh, David A. Contextual aspects of pain: why does the patient hurt? Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199668847.003.0014.
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The context in which osteoarthritis (OA) pain is experienced moderates and, to an extent, mediates its severity and impact. Context is both internal to the patient (e.g. genes, gender, age, comorbidities, psychological distress, and catastrophizing), and a consequence of external factors (e.g. social, healthcare, and work environment). Context influences how people report their pain, and also how the nervous system processes nociceptive information. Treatment contexts moderate and mediate therapeutic effectiveness, dependent on treatment expectations, beliefs, and risk evaluation. Uptake of treatments, both in primary and secondary care, is further influenced by the contexts in which they are offered. Understanding the nature and consequences of context helps explain heterogeneity between different people with OA pain, and opens avenues for potentially powerful interventions that could improve their quality of life. Context can be adjusted through the clinician–patient relationship and by targeting risk factors for poor outcome. Concurrent weight reduction, and psychological and physiotherapeutic interventions illustrate the use of combination therapy to address multiple contextual aspects of OA pain.
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Cleveland, Linda, and Kris Swarthout. Train to Tri: Your First Triathlon. Human Kinetics, 2017. http://dx.doi.org/10.5040/9781718225725.
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Swim. Bike. Run. If the combination of those three words gets you excited, then you need Train to Tri: Your First Triathlon. Written by experts with USA Triathlon (USAT), the largest multisport organization in the world, this book provides proven strategies, secrets, and advice to gear up for your first sprint-distance or standard-distance event. This is not another one-size-fits-all program. Train to Tri is designed so you can focus on the training you need most. You'll establish a baseline in each of the three phases: running, cycling, and swimming. You'll find bronze, silver, or gold levels of training for each phase, which can be combined and customized to your needs, your goals, and your lifestyle. Train to Tri is more than just training. It's total preparation. Featuring expert advice on selecting gear, staying motivated, overcoming challenges, preventing burnout, determining nutritional needs, and achieving recovery, it's a multifaceted plan for multisport success. If you're ready to go from athlete to triathlete, let Train to Tri and the experts at USAT lead the way.
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Gnudi, Luigi, Giorgio Gentile, and Piero Ruggenenti. The patient with diabetes mellitus. Edited by Giuseppe Remuzzi. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0149_update_001.
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About one third of patients with type 1 diabetes develop diabetic nephropathy long-term (usually not before at least 10 years of diabetes), though this proportion is falling as standards of care have risen. Nephropathy is strongly associated with other microvascular complications of diabetes, so that some degree of retinopathy is to be expected, and evidence of neuropathy is common. Patients with type 2 diabetes are equally susceptible, but this is an older group in which vascular disease and other pathologies are also more likely. The rise in type 2 diabetes accounts for diabetes being the most common recorded cause of end stage renal disease (ESRD) in the developed world.Diabetic nephropathy is characterized by a progression through hyperfiltration, microalbuminuria, hypertension, overt proteinuria, nephrotic syndrome, loss of GFR, to ESRD. Risk factors for developing it include genetic factors (though no major single gene effects have been identified), and quality of glycaemic control.The risk of progression can at early stages be reduced by improved glycaemic control, and control of hypertension also slows progression. However angiotensin converting enzyme inhibitors or receptor blockers (ACEi, ARB) are the standard of care for patients with microalbuminuria or overt proteinuria, as they have been shown to reduce the risk of renal endpoints. Combination therapy with both ACEi and ARB together has been associated with a high risk of AKI, hyperkalaemia and other adverse effects so is not generally recommended. Other promising agents in combination are under investigation but none adequately proven at this stage.Patients who reach ESRD have reduced survival on all modalities compared to age-matched patients with other diagnoses. Best rehabilitation and survival for those who are suitable is through renal transplantation, though combined pancreas-renal transplantation may offer still better outcomes for selected patients.
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Brennan, Matt. Kick It. Oxford University Press, 2020. http://dx.doi.org/10.1093/oso/9780190683863.001.0001.
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The drum kit—the combination of kick drum, snare drum, and cymbals—has provided the pulse of popular music from before the dawn of jazz up to the present day pop charts. This book is a provocative social history of the instrument that looks closely at key innovators in the development of the kit: inventors and manufacturers like the Ludwig and Zildjian dynasties, jazz icons like Gene Krupa and Max Roach, rock stars from Ringo Starr to Keith Moon, and popular artists who haven't always got their dues as drummers, such as Karen Carpenter and J Dilla. Addressing a seeming contradiction – the centrality of the drum kit on the one hand, and the general disparagement of drummers on the other—this book makes the case for the drum kit’s role as one of the most important and transformative musical inventions of the modern era. Going beyond its purely musical history, it uses the instrument to replay the wider history of the United States and to chart the rise of the drum kit’s global economic and cultural influence. Tackling the history of race relations, global migration, and the changing tension between high and low culture, it shows how the drum kit, drummers, and drumming helped change modern music—and society as a whole—from the bottom up.
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Karanika, Andromache. Wedding, Gender, and Performance in Ancient Greece. Oxford University PressOxford, 2024. http://dx.doi.org/10.1093/oso/9780198884576.001.0001.
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Abstract This book traces the wedding song tradition, its imagery, and its tropes as a genre that gets crystallized throughout the ages. It explores how wedding poetics permeates ancient Greek literature. It first analyzes how explicit or implicit matrimonial references shape archaic epic diction and become an integral part of epic discourse; orally circulating texts, such as wedding songs, could have a life of their own but, beyond their original context, could also become an integral part of a different genre, especially epic and drama. This work discusses the multiple platforms that enrich the wedding song tradition, including children’s songs, hymns, paeans, and ululations, arguing for a combination of ritualized discourse with ludic childhood poetics. With an approach from cognitive and trauma studies, such references can be more revealing of the female experience than previously acknowledged. This book resists the idea that a wedding constitutes an initiation ritual, arguing that what on the surface may seem like a transition to a new phase reveals other underlying trends that work against the concept of a passage. It further considers how emotion is staged and revisits the poetics of return by looking at patterns such as the eloping, returning, failed, and dead bride. Finally, the theme of separation and return as an exemplification of a distinct female nostos is revisited in female-authored poetry, which helps us decode the complex interweaving of wedding performances and lamentation, among other types of performance.