648 research outputs found
Portrait of John W. McCormack, Speaker of the House of Representatives.
No full textHandwritten inscription: \u27To Felton M. Johnston, my dearly valued friend with the respect and friendship of [John W. McCormack]\u27https://egrove.olemiss.edu/fmjohnston/1113/thumbnail.jp
Today's lifestyles, tomorrow's cancers: Trends in lifestyle risk factors for cancer in low- and middle-income countries
No full textBackground: The global burden of cancer is projected to increase from 13.3 to 21.4 million incident cases between 2010 and 2030 due to demographic changes alone, dominated by a growing burden in low- and middle-income countries (LMICs). Lifestyle risk factors for cancer are also changing in these countries and may further influence this burden.Design: We consider examples of changes already occurring in population-level distributions of tobacco and alcohol consumption, body weight, and reproductive lives of women to gauge the magnitude of their projected impact on cancer incidence in future decades.Results: Trends in lifestyle factors vary greatly between settings and by sex. Some common trends point to considerable increases in cancers of the (i) lung in men due to tobacco smoking; (ii) upper aerodigestive tract (UADT) due to increasing tobacco and alcohol consumption, worse in men; (iii) colon from increasing body mass index, and alcohol and tobacco consumption; and (iv) in women, breast due particularly to consistent international trends of younger age at menarche, smaller family size, and, at postmenopausal ages, increasing body weight.Conclusions: In many LMICs, the future cancer burden will be worsened by changing lifestyles. Affected common cancer sites likely to experience the largest increases are lung, colon, UADT, and breast. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved
Revisiting res ipsa loquitur: Mccormack v Sportsdirect.Com Fitness Limited considered
No full textIn this article, the author considers the recent decision of the Sheriff Appeal Court in Mccormack v Sportsdirect.Com Fitness Limited [2025] SAC (Civ) 15 in which the maxim res ipsa loquitur was found to have been incorrectly applied by the sheriff court.<br/
Author response
No full textPerforin-2 (MPEG1) is an effector of the innate immune system that limits the proliferation and spread of medically relevant Gram-negative, -positive, and acid fast bacteria. We show here that a cullin-RING E3 ubiquitin ligase (CRL) complex containing cullin-1 and βTrCP monoubiquitylates Perforin-2 in response to pathogen associated molecular patterns such as LPS. Ubiquitylation triggers a rapid redistribution of Perforin-2 and is essential for its bactericidal activity. Enteric pathogens such as
Yersinia pseudotuberculosis
and enteropathogenic
Escherichia coli
disarm host cells by injecting cell cycle inhibiting factors (Cifs) into mammalian cells to deamidate the ubiquitin-like protein NEDD8. Because CRL activity is dependent upon NEDD8, Cif blocks ubiquitin dependent trafficking of Perforin-2 and thus, its bactericidal activity. Collectively, these studies further underscore the biological significance of Perforin-2 and elucidate critical molecular events that culminate in Perforin-2-dependent killing of both intracellular and extracellular, cell-adherent bacteria.
DOI:
http://dx.doi.org/10.7554/eLife.06505.001
A wide range of bacteria and other microbes can infect animals and cause disease. Throughout evolution, these microbes and their hosts have been fighting never ending arms races in which the microbes deploy ever more elaborate weapons, while the hosts adapt to defend themselves. An animal's first line of defense is provided by its ‘innate’ immune system. This system is activated by the general features of microbial cells; for example, the molecules that make up the walls surrounding most bacteria. Microbes must defeat the innate immune system in order to cause disease, and ultimately to spread from one host to the next.
One component of innate immunity is a protein called Perforin-2 that is present in most, if not all, animal cells. This protein forms pores on bacterial cells, causing them to split open and die. However, it was not clear how Perforin-2 is switched on and what, if anything, bacteria do to counteract it. To address these questions, McCormack et al. infected human and mice cells with bacteria that cause serious diseases of the digestive tract.
The experiments show that when animal cells detect bacteria, or merely a fragment of their cell wall, a specific group of proteins, called the CRL complex, attaches a molecule called ubiquitin to Perforin-2. Ubiquitin works much like the shipping label of a package, enabling the efficient targeting of Perforin-2 to the invading bacteria. McCormack et al. also show that some bacteria use a protein called a cell cycle inhibiting factor (or Cif for short) to inhibit the CRL complex. This blocks the ubiquitin labeling of Perforin-2, which renders it a useless weapon that can no longer be directed towards bacteria.
Mice that are infected with a bacterium called
Yersinia pseudotuberculosis
become seriously unwell and often die. However, McCormack et al. found that mice infected with mutant
Y. pseudotuberculosis
that lacked Cif remained healthy. Also, mice that lacked Perforin-2 are highly susceptible to infectious diseases. McCormack et al.'s findings reveal how Perforin-2 is activated during the innate immune response and how some bacteria can defeat this pivotal defense. In the current age of antibiotic resistant bacteria, these studies may spur the development of new drugs that restore or increase the activity of Perforin-2.
DOI:
http://dx.doi.org/10.7554/eLife.06505.00
Fetal growth and subsequent risk of breast cancer: results from long term follow up of Swedish cohort.
No full textOBJECTIVE: To investigate whether size at birth and rate of fetal growth influence the risk of breast cancer in adulthood. DESIGN: Cohort identified from detailed birth records, with 97% follow up. SETTING: Uppsala Academic Hospital, Sweden. PARTICIPANTS: 5358 singleton females born during 1915-29, alive and traced to the 1960 census. MAIN OUTCOME MEASURES: Incidence of breast cancer before (at age or = 50 years) the menopause. RESULTS: Size at birth was positively associated with rates of breast cancer in premenopausal women. In women who weighed > or =4000 g at birth rates of breast cancer were 3.5 times (95% confidence interval 1.3 to 9.3) those in women of similar gestational age who weighed <3000 g at birth. Rates in women in the top fifths of the distributions of birth length and head circumference were 3.4 (1.5 to 7.9) and 4.0 (1.6 to 10.0) times those in the lowest fifths (adjusted for gestational age). The effect of birth weight disappeared after adjustment for birth length or head circumference, whereas the effects of birth length and head circumference remained significant after adjustment for birth weight. For a given size at birth, gestational age was inversely associated with risk (P=0.03 for linear trend). Adjustment for markers of adult risk factors did not affect these findings. Birth size was not associated with rates of breast cancer in postmenopausal women. CONCLUSIONS: Size at birth, particularly length and head circumference, is associated with risk of breast cancer in women aged <50 years. Fetal growth rate, as measured by birth size adjusted for gestational age, rather than size at birth may be the aetiologically relevant factor in premenopausal breast cancer
Review of George Eliot in Society: Travels Abroad and Sundays at the Priory
No full textThis is a welcome and wholly worthwhile extension of the author\u27s George Eliot\u27s English Travels: Composite Characters and Coded Communication (2005), a densely written and stimulating examination of places and people in Eliot\u27s life which have some resonance, in varying degrees of coding, from the seemingly casual to the subtly integrated, in her published work. McCormack there defined three categories of place identification. These range from \u27absolute certainties\u27 through \u27pretty good cases\u27 to \u27alluring, probable, but irretrievably speculative suppositions\u27, categories certainly applicable to herpresent study, in which her dedication and saturation in George Eliot, the works, the life, and a wide range of biographical and critical commentary, is again evident. It is a direct invitation to see and feel places and people, decode traits, pick up on similarities, mine differences, above all, be aware. McCormack\u27s method is one of intimate identification with the life and the writing life.
The main thrust demonstrates how Eliot\u27s social agenda, with the Sunday salons from 1869 onwards at the Priory as the focus, feeds into her fiction - and initially her poetry - together with comparable assimilations from her travelling life in Europe with Lewes from 1854 onwards up to the fraught honeymoon with Cross in 1880. Throughout, the Haight contention that Eliot was largely reclusive, a view commonly supported, is subjected to intense scrutiny and is vigorously disputed. The Sunday gatherings, carefully assembled, would suggest that Eliot enjoyed being the centre of a salon of her own making, her essay on Madame de Sable providing precursory evidence. The importance of Lewes as initiator, manager, socializing facilitator with an eye alert as always to publishing and critical opportunities, is integral. McCormack uses his unpublished journals and diaries, supplementing them with a detailed attention to known biographical sources which she carefully sifts for reliability or bias
‘…a tiny part of that greater circum-terrestrial grid’: A Conversation with Mike McCormack
No full textThis is the author accepted manuscript. The final version is available from Edinburgh University Press via the DOI in this recor
Heterogeneity of breast cancer risk within the South Asian female population in England: a population-based case-control study of first-generation migrants.
No full textSouth Asian women in England have a lower breast cancer risk than their English-native counterparts, but less is known about variations in risk between distinct South Asian ethnic subgroups. We used the data from a population-based case-control study of first-generation South Asian migrants to assess risks by ethnic subgroup. In all, 240 breast cancer cases, identified through cancer registries, were individually matched on age and general practitioner to two controls. Information on the region of origin, religious and linguistic background, and on breast cancer risk factors was obtained from participants. Breast cancer odds varied significantly between the ethnic subgroups (P=0.008), with risk increasing in the following order: Bangladeshi Muslims (odds ratio (OR) 0.33, 95% confidence interval (CI): 0.10, 1.06), Punjabi Hindu (OR 0.59, 95% CI: 0.33, 1.27), Gujarati Hindu (1=reference group), Punjabi Sikh (OR 1.23, 95% CI: 0.72, 2.11) and Pakistani/Indian Muslims (OR 1.76, 95% CI: 1.10, 2.81). The statistically significant raised risk in Pakistani/Indian Muslims increased with adjustment for socioeconomic and reproductive risk factors (OR 2.12, 95% CI: 1.25, 3.58), but was attenuated, and no longer significant, with further adjustment for waist circumference and intake of nonstarch polysaccharides and fat (OR 1.49, 95% CI: 0.85, 2.63). These findings reveal differences in breast cancer risk between South Asian ethnic subgroups, which were not fully explained by reproductive differences, but were partly accounted for by diet and body size
Review of George Eliot\u27s Travels: Composite Characters and Coded Communications.
No full textWhen we think of George Eliot, the word \u27travels\u27 is likely to suggest journeys to far-flung places in foreign lands, but considered in an English setting, she seems to be locked in either Warwickshire or London. Kathleen McCormack, however, shows how widely George Eliot travelled in her own country, so widely that she made over fifty visits to English places and only thirty to foreign destinations. Indeed, \u27widely\u27 is a word that stimulates Kathleen McCormack\u27s imagination as she has revealed in an earlier work, George Eliot and Intoxication (2000), in which the last word, \u27Intoxication\u27, is interpreted in its widest sense. Her article, \u27Widely Sundered Elements\u27 (George Eliot Review, 2000) prepares the reader for this more detailed and ambitious survey which should fascinate anyone interested in English settings and their relevance to the writings of George Eliot (or \u27Evans\u27 as she at first forbiddingly if fashionably calls her). After an exploration of well-known haunts in Warwickshire, chapter headings invite us to visit less familiar places: \u27Seasides\u27, \u27Islands\u27, \u27Country Shires\u27, \u27Spas\u27, \u27Whitby, Devon, Oxford, Surrey\u27 and \u27Country Houses\u27. The Leweses rarely travelled for pleasure alone; we are shown how they journeyed for other reasons too: for health, for research, for escape from gossip, for specimen-gathering on English beaches, for visits to museums, art galleries, cathedrals, for the refreshment of working in different places. Although the railway must have helped, they were prepared to endure all kinds of discomfort in England and on the Continent for the sake of fresh environments. The author of this interesting new book describes their travels as purposeful and productive unlike the dreamy, fruitless voyage of Maggie Tulliver down the river and unlike her subsequent \u27boarding a coach without checking its destination\u27
Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis.
No full textMammographic features are associated with breast cancer risk, but estimates of the strength of the association vary markedly between studies, and it is uncertain whether the association is modified by other risk factors. We conducted a systematic review and meta-analysis of publications on mammographic patterns in relation to breast cancer risk. Random effects models were used to combine study-specific relative risks. Aggregate data for > 14,000 cases and 226,000 noncases from 42 studies were included. Associations were consistent in studies conducted in the general population but were highly heterogeneous in symptomatic populations. They were much stronger for percentage density than for Wolfe grade or Breast Imaging Reporting and Data System classification and were 20% to 30% stronger in studies of incident than of prevalent cancer. No differences were observed by age/menopausal status at mammography or by ethnicity. For percentage density measured using prediagnostic mammograms, combined relative risks of incident breast cancer in the general population were 1.79 (95% confidence interval, 1.48-2.16), 2.11 (1.70-2.63), 2.92 (2.49-3.42), and 4.64 (3.64-5.91) for categories 5% to 24%, 25% to 49%, 50% to 74%, and > or = 75% relative to < 5%. This association remained strong after excluding cancers diagnosed in the first-year postmammography. This review explains some of the heterogeneity in associations of breast density with breast cancer risk and shows that, in well-conducted studies, this is one of the strongest risk factors for breast cancer. It also refutes the suggestion that the association is an artifact of masking bias or that it is only present in a restricted age range
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