Dietary interventions affecting chylomicron and chylomicron remnant clearance

Interest in effects of diet on postprandial lipoproteins has increased in recent years as a result of accumulating evidence for adverse cardiovascular consequences of elevated concentrations of triglyceride rich lipoproteins. Particular attention has been given to ability of different fatty acids to modulate postprandial lipoprotein responses because of evidence for both harmful and protective cardiovascular properties of the saturated, monounsaturated and ω-6 and ω-3 polyunsaturated fatty acid (PUFA) classes. Evidence for direct atherogenic properties of chylomicron remnants has led to attempts to monitor effects of diet specifically on this lipoprotein class. Limitations in the methods employed to measure chylomicron remnants and the small number of human studies which have evaluated effects of meal, and background diet, fatty acid composition, makes it difficult to draw definitive conclusions at the present time. However consideration of data from both animal and human studies tends to support the conclusion that diets, and meals, rich in PUFA (particularly long chain ω-3 PUFA), result in attenuated postprandial responses of the intestinally-derived lipoproteins. Attenuated responses to high PUFA meals appear to be due to greater rates of clearance and greater activation of lipoprotein lipase (LPL). Attenuated responses to high PUFA background diets may be due to adaptive changes involving both accelerated rates of clearance in peripheral tissues and liver, as well as decreased output of the competitor for chylomicron clearance, very low density lipoprotein (VLDL).

N-nitroso compound exposure-associated transcriptomic profiles are indicative of an increased risk for colorectal cancer

Endogenous formation of N-nitroso compounds (NOCs), which are known animal carcinogens, could contribute to human carcinogenesis but definitive evidence is still lacking. To investigate the relevance of NOCs in human colorectal cancer (CRC) development, we analyzed whole genome gene expression modifications in human colon biopsies in relation to fecal NOC exposure. We had a particular interest in patients suffering from intestinal inflammation as this may stimulate endogenous NOC formation, and consequently predispose to CRC risk. Inflammatory bowel disease (IBD) patients diagnosed with ulcerative colitis and irritable bowel syndrome patients without inflammation, serving as controls, were therefore recruited. Fecal NOC were demonstrated in the majority of subjects. By associating gene expression levels of all subjects to fecal NOC levels, we identified a NOC exposure-associated transcriptomic response that suggests that physiological NOC concentrations may potentially induce genotoxic responses and chromatin modifications in human colon tissue, both of which are linked to carcinogenicity. In a network analysis, chromatin modifications were linked to 11 significantly modulated histone genes, pointing towards a possible epigenetic mechanism that may be relevant in comprehending NOC-induced carcinogenesis. In addition, pro-inflammatory transcriptomic modifications were identified in visually non-inflamed regions of the IBD colon. However, fecal NOC levels were slightly but not significantly increased in IBD patients, suggesting that inflammation did not strongly stimulate NOC formation. We conclude that NOC exposure is associated with gene expression modifications in the human colon that may suggest a potential role of these compounds in CRC development.

The uncertainty of valuation

Valuation is often said to be “an art not a science” but this relates to the techniques employed to calculate value not to the underlying concept itself. Valuation is the process of estimating price in the market place. Yet, such an estimation will be affected by uncertainties. Uncertainty in the comparable information available; uncertainty in the current and future market conditions and uncertainty in the specific inputs for the subject property. These input uncertainties will translate into an uncertainty with the output figure, the valuation. The degree of the uncertainties will vary according to the level of market activity; the more active a market, the more credence will be given to the input information. In the UK at the moment the Royal Institution of Chartered Surveyors (RICS) is considering ways in which the uncertainty of the output figure, the valuation, can be conveyed to the use of the valuation, but as yet no definitive view has been taken apart from a single Guidance Note (GN5, RICS 2003) stressing the importance of recognising uncertainty in valuation but not proffering any particular solution. One of the major problems is that Valuation models (in the UK) are based upon comparable information and rely upon single inputs. They are not probability based, yet uncertainty is probability driven. In this paper, we discuss the issues underlying uncertainty in valuations and suggest a probability-based model (using Crystal Ball) to address the shortcomings of the current model.

Sequential methods for pharmacogenetic studies

A study or experiment can be described as sequential if its design includes one or more interim analyses at which it is possible to stop the study, having reached a definitive conclusion concerning the primary question of interest. The potential of the sequential study to terminate earlier than the equivalent fixed sample size study means that, typically, there are ethical and economic advantages to be gained from using a sequential design. These advantages have secured a place for the methodology in the conduct of many clinical trials of novel therapies. Recently, there has been increasing interest in pharmacogenetics: the study of how DNA variation in the human genome affects the safety and efficacy of drugs. The potential for using sequential methodology in pharmacogenetic studies is considered and the conduct of candidate gene association studies, family-based designs and genome-wide association studies within the sequential setting is explored. The objective is to provide a unified framework for the conduct of these types of studies as sequential designs and hence allow experimenters to consider using sequential methodology in their future pharmacogenetic studies.

Zugzwangs in chess studies

Van der Heijden’s ENDGAME STUDY DATABASE IV, HHDBIV, is the definitive collection of 76,132 chess studies. The zugzwang position or zug, one in which the side to move would prefer not to, is a frequent theme in the literature of chess studies. In this third data-mining of HHDBIV, we report on the occurrence of sub-7-man zugs there as discovered by the use of CQL and Nalimov endgame tables (EGTs). We also mine those Zugzwang Studies in which a zug more significantly appears in both its White-to-move (wtm) and Black-to-move (btm) forms. We provide some illustrative and extreme examples of zugzwangs in studies.

Internal rents and corporate property management: a study into the use of internal rents in UK corporate organisations

Research in the late 1980s showed that in many corporate real estates users were not fully aware of the full extent of their property holdings. In many cases, not only was the value of the holdings unknown, but there was uncertainty over the actual extent of ownership within the portfolio. This resulted in a large number of corporate occupiers reviewing their property holdings during the 1990s, initially to create a definitive asset register, but also to benefit from an more efficient use of space. Good management of corporately owned property assets is of equal importance as the management of other principal resources within the company. A comprehensive asset register can be seen as the first step towards a rational property audit. For the effective, efficient and economic delivery of services, it is vital that all property holdings are utilised to the best advantage. This requires that the property provider and the property user are both fully conversant with the value of the property holding and that an asset/internal rent/charge is made accordingly. The advantages of internal rent charging are twofold. Firstly, it requires the occupying department to “contribute” an amount to the business equivalent to the open market rental value of the space that it occupies. This prevents the treating of space as a free good and, as individual profit centres, each department will then rationalise its holdings to minimise its costs. The second advantage is from a strategic viewpoint. By charging an asset rent, the holding department can identify the performance of its real estate holdings. This can then be compared to an internal or external benchmark to help determine whether the company has adopted the most efficient tenure pattern for its properties. This paper investigates the use of internal rents by UK-based corporate businesses and explains internal rents as a form of transfer pricing in the context of management and responsibility accounting. The research finds that the majority of charging organisations introduced internal rents primarily to help calculate true profits at the business unit level. However, less than 10% of the charging organisations introduced internal rents primarily to capture the return on assets within the business. There was also a sizeable element of the market who had no plans to introduce internal rents. Here, it appears that, despite academic and professional views that internal rents are beneficial in improving the efficient use of property, opinion at the business and operational level has not universally accepted this proposition.

A cognitive and psycholinguistic investigation of neologisms

Background: Jargon aphasia with neologisms (i.e., novel nonword utterances) is a challenging language disorder that lacks a definitive theoretical description as well as clear treatment recommendations (Marshall, 2006). Aim: The aims of this two part investigation were to determine the source of neologisms in an individual with jargon aphasia (FF), to identify potential facilitatory semantic and/or phonological cuing effects in picture naming, and to determine whether the timing of the cues relative to the target picture mediated the cuing advantage. Methods and Procedures: FF’s underlying linguistic deficits were determined using several cognitive and linguistic tests. A series of computerized naming experiments using a modified version of the 175 item-Philadelphia Naming Test (Roach, Schwartz, Martin, Grewal, & Brecher, 1996) manipulated the cue type (semantic versus phonological) and relatedness (related versus unrelated). In a follow-up experiment, the relative timing of phonological cues was manipulated to test the effect of timing on the cuing advantage. The accuracy of naming responses and error patterns were analyzed. Outcome and Results: FF’s performance on the linguistic and cognitive test battery revealed a severe naming impairment with relatively spared word and nonword repetition, auditory comprehension of words and monitoring, and fairly well preserved semantic abilities. This performance profile was used to evaluate various explanations for neologisms including a loss of phonological codes, monitoring failure, and impairments in semantic system. The primary locus of his deficit appears to involve the connection between semantics to phonology, specifically, when word production involves accessing the phonological forms following semantic access. FF showed a significant cuing advantage only for phonological cues in picture naming, particularly when the cue preceded or coincided with the onset of the target picture. Conclusions: When integrated with previous findings, the results from this study suggest that the core deficit of this and at least some other jargon aphasics is in the connection from semantics to phonology. The facilitative advantage of phonological cues could potentially be exploited in future clinical and research studies to test the effectiveness of these cues for enhancing naming performance in individuals like FF.

Retirement and succession on the family farm

For farmers, the decision as to when to retire is probably one of the hardest that they will have to face during their working lives. The business of farming brings special circumstances which means that retirement is more often a process than a definitive action. This paper seeks firstly to clarify those special circumstances, and then, by means of flow charts, to identify the key decisions which must be faced if the retirement is to be successful. The practise of handing on the farmland and the other business assets to the next generation are regarded as separate but interrelated stages in the process of retirement, both having legal, financial and human consequences which are considered. By way of conclusion, the parameters for a successful retirement are considered, both from the standpoint of the retirer and of the successor.

The uncertainty of valuation

Valuation is often said to be “an art not a science” but this relates to the techniques employed to calculate value not to the underlying concept itself. Valuation is the process of estimating price in the market place. Yet, such an estimation will be affected by uncertainties. Uncertainty in the comparable information available; uncertainty in the current and future market conditions and uncertainty in the specific inputs for the subject property. These input uncertainties will translate into an uncertainty with the output figure, the valuation. The degree of the uncertainties will vary according to the level of market activity; the more active a market, the more credence will be given to the input information. In the UK at the moment the Royal Institution of Chartered Surveyors (RICS) is considering ways in which the uncertainty of the output figure, the valuation, can be conveyed to the use of the valuation, but as yet no definitive view has been taken. One of the major problems is that Valuation models (in the UK) are based upon comparable information and rely upon single inputs. They are not probability based, yet uncertainty is probability driven. In this paper, we discuss the issues underlying uncertainty in valuations and suggest a probability-based model (using Crystal Ball) to address the shortcomings of the current model.

Sequence analysis and distribution in Salmonella enterica serovars of IS3-like elements

The genome of Salmonella enterica serovar Enteritidis was shown to possess three IS3-like insertion elements, designated IS1230A, B and C, and each was cloned and their respective deoxynucleotide sequences determined. Mutations in elements IS1230A and B resulted in frameshifts in the open reading frames that encoded a putative transposase to be inactive. IS1230C was truncated at nucleotide 774 relative to IS1230B and therefore did not possess the 3' terminal inverted repeat. The three IS1230 derivatives were closely related to each other based on nucleotide sequence similarity. IS1230A was located adjacent to the sef operon encoding SEF14 fimbriae located at minute 97 of the genome of S. Enteritidis. IS1230B was located adjacent to the umuDC operon at minute 42.5 on the genome, itself located near to one terminus of an 815-kb genome inversion of S. Enteritidis relative to S. Typhimurium. IS1230C was located next to attB, the bacteriophage P22 attachment site, and proB, encoding gamma-glutamyl phosphate reductase. A truncated 3' remnant of IS1230, designated IS1230T, was identified in a clinical isolate of S. Typhimurium DT193 strain 2391. This element was located next to attB adjacent to which were bacteriophage P22-like sequences. Southern hybridisation of total genomic DNA from eighteen phage types of S. Enteritidis and eighteen definitive types of S. Typhimurium showed similar, if not identical, restriction fragment profiles in the respective serovars when probed with IS1230A.

Analysis of expression of flagella by Salmonella enterica serotype Typhimurium by monoclonal antibodies recognising both phase specific and common epitopes

Monoclonal antibodies specific for phase 1 ("i" antigen), phase 2 ("1,2" antigen) and common epitopes of the flagellins of Salmonella enterica serotype Typhimurium were raised. Having confirmed their specificity, the monoclonal antibodies were used to develop semi-quantitative ELISAs in order to assess the relative expression of the two phases by strains of Typhimurium. The majority of Typhimurium strains representative of a wide cross-section of definitive types from animal and environmental sources preferentially expressed phase 1 antigen in vitro. DT40 strains were unique in expressing phase 2 preferentially. The ratio of phase 1 to phase 2 expressed by strains tended to be constant for any one strain when strains were grown on a number of conventional laboratory media. However, the ratio of phases was shown to be modulated by incubation at 42 degreesC and buffering media at pH values, notably 4.5, other than neutral. Selenite broth and Rambach media repressed flagellation. Crown Copyright (C) 2001 Published by Elsevier Science B.V. All rights reserved.

Variation in clonality and antibiotic-resistance genes among multiresistant Salmonella enterica serotype typhimurium phage-type U302 (MR U302) from humans, animals, and foods

Since 1990 multiresistant (MR) Salmonella enterica serotype Typhimurium definitive phage-type (DT) 104 (MR DT104) and closely related phage types have emerged as a worldwide health problem in humans and food animals. In this study the presence of the bla(CARB-2) (ampicillin), cmlA (chloramphenicol), aadA2 (streptomycin/spectinomycin), sul1 (sulphonamide), and tetG (tetracycline) resistance genes in isolates of one such phage type, U302, have been determined. In addition bla(TEM) I primers have been used for the detection of TEM-type beta-lactamases. Isolates have also been characterized by plasmid profile and pulsed field gel electrophoresis (PFGE). Thirty-three of 39 isolates were positive for blaCARB-2, cmlA, aadA2, sul1 and tetG, four for bla(TEM), aadA2 and sul1, one for aadA2 and sul1, and one for blaTEM only. bla(TEM)-mediated ampicillin resistance was transferred to Escherichia coli K12 from three isolates along with other resistance markers, including resistance to chloramphenicol, streptomycin, spectinomycin, sulphonamides, and tetracyclines. Strains carried up to 6 plasmids and 34 plasmid profiles were identified. Although the majority of strains (33/39) produced a PFGE profile identical to that predominant in MR DT104, six different patterns were generated demonstrating the presence of various clones within MR U302. The results show that the majority of the MR U302 strains studied possessed the same antibiotic resistance genes as MR DT104. However, isolates with distinctive PFGE patterns can have different mechanisms of resistance to ampicillin, chloramphenicol, streptomycin, sulphonamides, and tetracyclines. Such resistance genes may be borne on transmissible plasmids.

An obscured tradition: the sonnet and its fourteen-line predecessors

The sonnet in English is usually located as a sixteenth-century innovation, firmly linked to Italian influences, and frequently associated with a distinctively modern consciousness. Yet the speed and comfort with which the form settled into English reflects the fact that the sonnet per se was preceded by a longstanding tradition of 14-line poems in English written in forms derived from French. Indeed, in terms of formal features, the earliest sonnets in English frequently fray into earlier forms, sharing more with the roundel than with later sonnets. This article considers a number of features of style and content that various writers on the sonnet have argued to be characteristic, sometimes definitive, of the sonnet. These features include repetition, formal unity/division of octave and sestet, use of the volta, asymmetry, argument and development, and a preoccupation with contradictions and the self. The article shows that, while it is true that these features are characteristic of many sonnets, they are not peculiarly characteristic of sonnets, and they can all be found in earlier 14-line poems. Furthermore, a number of the earliest sonnets in English do not themselves possess these ‘sonnet-like’ characteristics. The otherness and the modernity of the sonnet have thus been overstated.

Le rêve du roi Flualis : mise en texte et mise en image d'enjeux épiques et hagiographiques dans le Roman de Merlin

L'illustration de la plupart des manuscrits de la Suite Vulgate met l'accent sur l'intervention prophétique de Merlin et sur l'accomplissement des désastres qu'il annonce au roi de Jérusalem Flualis, replaçant l'épisode dans une série de passages où Merlin fait la démonstration de ses pouvoirs surnaturels et de sa capacité à interpréter les songes. Pourtant, dans un petit groupe d'ouvrages, l'illustration se focalise sur la conversion ultime de Flualis et de sa femme, insistant sur le caractère exemplaire et édifiant d'un épisode qui propose une résolution des relations entre païens et chrétiens différente de celles habituellement mises en scène dans l'univers à coloration épique de la continuation.

Contribution of the geriatrician to the management of cancer in older patients

With an increasingly aged population, many patients will present with cancer in their 80s and 90s. Although some may be very fit, frail individuals will require the input of geriatricians to aid in the assessment of co-existing morbidity, in an attempt to assess those most likely to benefit from active treatment of their cancer, and those in whom the ‘giants of geriatric medicine’ require special consideration before undergoing definitive cancer therapy. The role of the geriatrician in assessment and management of such patients, together with communication and end of life care, may be more important in ensuring a good quality of life, than the cancer therapy itself. Whilst numbers of geriatricians will not be adequate to care for all elderly patients with cancer, a variety of assessment scales will help target financial and manpower resources to those most at risk.