Important Warning Research Articles

Smoking, smoking cessation and aortic arch calcification in older Chinese: The Guangzhou Biobank Cohort Study

Objective To study the association between smoking, smoking cessation and aortic arc calcification (AAC) in an older Chinese population. Methods A total of 3022 men and 7279 women aged 50–85 years were recruited and received a medical check-up including measurement of fasting plasma vascular risk factors. Two radiologists reviewed the posterior–anterior plain chest X-ray radiographs and assessed AAC together. Information on smoking status, socioeconomic and lifestyle factors was collected. Results The crude prevalence of AAC in men (38.58%) was lower than that in women (41.37%). The adjusted odds ratios of AAC increased significantly across never, ex- and current smokers in both genders. Dose–response relationships were observed among current smokers for smoking amount (cigarettes/day), smoking duration (years) and cigarette pack-years in both genders (all p < 0.01). The odds ratios decreased significantly ( p = 0.018) with longer duration of quitting in light ex-smoking men (<23.5 pack-years) but showed no beneficial effect ( p = 0.72) for heavy ex-smokers (≥23.5 pack-years). Conclusion Smoking increased the risk of AAC in Chinese, while smoking cessation decreased the risk only in male light ex-smokers. Chest X-ray is a cheap and simple method to detect AAC, which should be an important warning signal for immediate smoking cessation.

Credit Spread Widening Risk in Portfolios: Pricing Techniques and Sensitivity Measures

Nowadays, contrarily to what was happening just a few years ago, credit risk soaks the majority of securities allocated in the banks’ trading portfolios. The development of securitisation techniques and the parallel refinement of pricing models allowed the transfer of this risk in new forms, more digestible even for the most cautious investors. After the understandable initial suspicion towards the innovation, corporate bonds, asset backed securities and credit linked notes have gradually populated new portfolios, introducing a considerable component of income, but, at the same time, exposing the related fair values to the risk of credit spread fluctuations. It is possible that some risk management system cannot fully capture the risk of devaluation of credit risky instruments that not always arises from real changes in the solvency conditions of the borrowers, but, more frequently, is due to the changes in risk perception for investors. Indeed, behavioural mechanisms (e.g., flight to quality) may be triggered by isolated events (e.g., some important downgrade or profit warning) producing, at least in the short term, a general spread widening resulting in losses for all credit risky securities. Treating this risk class as internal to interest-rate risk often leads to fair value inaccuracy and under-evaluation of value-at-risk. This is true for every financial instrument, but is more evident for floating rate notes that, while show a low interest rate risk, often imply high credit spread sensitivities. Therefore, starting from the typical pricing models for plain vanilla bonds, we explore the possibility of improving the current pricing techniques in order to isolate spread risk and the mere interest-rate risk.

Systemic determinants of gene evolution and function

Mol Syst Biol. 1: 2005.0021 What determines a gene's evolutionary rate? In particular, does it depend solely on functional constraints imposed on the structure of the encoded protein or are there higher‐level factors related to the selection at the organismal level? These questions seem to be among the most fundamental ones in biology because comprehensive answers will reveal the nature of the links between genome evolution and the phenotypes of organisms. A recent study by Wall et al (2005) proves more convincingly than ever before that systemic determinants of gene evolution rate do exist, and an intriguing paper by Fraser (2005) sheds light on some of the underlying mechanisms. However, a recent report by Coulomb et al (2005) issues an important warning by showing that some of the intuitively plausible connections discovered by Systems Biology may be due to biases in the data. Nearly 30 years ago, Wilson et al (1977) put forward a general proposition that may be called the rate‐dispensability conjecture—the evolutionary rate should be a function of, firstly, the constraints on the function of the given gene (protein) and, secondly, the ‘importance’ (fitness effect of knockout or dispensability) of the gene for the organism: R i = f(P i )f(Q i ) ( R i is the rate of evolution of the given protein, P i is the probability that a substitution is compatible with the function of this protein, and Q i is the probability that the organism survives and reproduces without this protein). The prediction, thus, is that essential (indispensable) genes, on average, should evolve slower than nonessential genes. This conjecture generally follows from Kimura's neutral theory of evolution but is nontrivial given the broad variance of structural–functional constraints on proteins, regardless of their dispensability; in principle, this variance could …

Localization of slow wave activity in patients with tumor-associated epilepsy.

Brain tumors are frequently accompanied by abnormal low frequency magnetic activity (ALFMA). The prevalence and clinical meaning of ALFMA are not well known, although a relation with epileptic brain tissue has been suggested. We studied the prevalence, characteristics and clinical correlates of ALFMA in 20 patients with brain tumors. In 20 patients with clinical seizures due to a supratentorial tumor, MEG was performed, followed by MR imaging. MEG signals were band pass-filtered (1-4 Hz); the sources of this activity were localized and projected onto the MRI of the patient. Peritumoral ALFMA could be detected in 13 of 20 patients. A pattern of ALFMA distribution around the tumor could be recognized. In eight cases ALFMA also appeared to be localized within the tumor. In three cases ALFMA was also detected in peritumoral white matter. Automatic detection of abnormal delta-activity in patients with a brain tumor and seizures can be performed in a clinical setting. When detected, ALFMA is mostly present in circumscribed regions around the tumor. Presence of ALFMA within the tumor might be an important warning signal for the neurosurgeon that the tumor area comprises functional brain tissue.

Long-term antibiotic resistance surveillance of gram-negative pathogens suggests that temporal trends can be used as a resistance warning system.

Antibiotic resistance among Gram-negative bacteria and antibiotic consumption were investigated at the Karolinska Hospital, Stockholm, Sweden over a 12-y period. The investigation showed an increase in ciprofloxacin resistance of Escherichia coli from 0% in 1991 to 7% in 1997 and to 11% in 1999. Resistance among Pseudomonas aeruginosa isolates to ciprofloxacin increased from 2.5% in 1991 to 9.0% in 1997 and to 13% in 1999. Resistance levels for norfloxacin showed the same high statistical significance in terms of the temporal trend. A more detailed analysis showed higher resistance against norfloxacin in specific wards. Relationships between antibiotic use and antibiotic susceptibility showed different patterns. The increased ciprofloxacin resistance of E. coli and P. aeruginosa during the study period was paralleled by an increased consumption of quinolones. During the 12-y study period the total use of cephalosporins increased 2.5-fold, while the levels of E. coli resistance to cefuroxime and cefotaxime remained stable. A third pattern was seen with trimethoprim-sulfamethoxazole, namely increasing resistance of E. coli as the use of trimethoprim-sulfamethoxazole declined. The analysis of resistance levels and antibiotic consumption in the present study suggests different mechanisms for the increased resistance. The significant trend of increased resistance to antibiotics over time constitutes an important warning system.

Some Political Economy Aspects of EMU

European Monetary Union (EMU) is here at last, but according to economists’ traditional perspective on economic policy making, it should not be. Given the nontrivial nature of this occurrence, it offers an important warning signal that policy economists need to reexamine our assumptions about the forces generating economic policy decisions. Economists, of course, have strong preferences for analysis based on assumptions of rationality and efficiency, and with good reason. When we turn from the analysis of market behavior to that of policy making, however, the simple application of these assumptions does not stand up as well. The economists’ traditional approach in this area has been to attempt to figure out what policy will maximize aggregate economic efficiency, and then assume that this is what the government will adopt. This benign dictator or optimal social planner approach is not totally devoid of predictive power. Similar predictions can be derived from idealized models of democratic processes, and are roughly approximated by the fully informed median voter model of public choice analysis. Most economic policy choices cannot be explained in this manner, however, and the creation of EMU is no exception. The choice of international currency policy has been a major area of monetary research. The theory of optimum currency area (OCA), pioneered by Robert Mundell, focuses precisely on the factors that influence the economic costs and benefits of adopting fixed versus flexible exchange rates. Over time, the number of criteria found to be relevant for this cost–benefit analysis has

The protection system of the superconducting coils in the Barrel Toroid of ATLAS

An analysis of the discharge of the Barrel Toroid under several operating conditions has been carried out. The main critical parameters of the discharge (i.e. the maximum temperature inside the coils, the maximum temperature gradient, the maximum voltage at the coil ends and the maximum decentering forces acting on the BT and ECT magnets) have been calculated for several operating conditions (heaters on, heaters off, short circuit with heaters on or off). The aim of this analysis is to provide a cross check of the protection design of the Barrel Toroid coils with an independent study. The results validate the choice to use a low value of dump resistance, and give some important warning in the case of heater failure or presence of a short circuit.

Start Low and Go Slow: Dosing of Antipsychotic Medications in Elderly Patients With Dementia

I read with interest the review article by Yeager et al¹on the management of the behavioral manifestations of dementia. The article included a treatment algorithm suggesting a management strategy for the demented patient with aberrant behavior. The algorithm appropriately emphasized nonpharmacologic approaches as the optimal initial management strategy for these patients. For the patient who is unresponsive to nonpharmacologic measures, the algorithm recommended the initiation of a trial of antipsychotic therapy for 8 weeks. The suggested regimens include haloperidol, 2.5 mg at bedtime, or thioridazine, 25 mg at bedtime, with titration of these doses according to the patient's response to therapy. Buried in the legend of the figure describing the treatment algorithm was a recommendation that a lower starting dose is recommended in the elderly. However, no dosing recommendations were given and the less-than-careful reader could easily miss this important warning. Since the elderly constitute the vast majority

Advertising bans and product demand: how does marketing affect demand for a differentiated product?

Applied economists have made extensive use of product category time series studies to investigate the effects that an advertising ban might have on markets for potentially harmful products such as tobacco and alcohol. This paper argues that such studies can cast little light on the question, partly because they contain no plausible hypothesis of how advertising influences demand in a market for differentiated products. This paper extracts such an hypothesis from literature on the psychology of consumer behaviour, and uses it in simple economic model of a differentiated product market. The analytical results are sensitive to the precise assumptions made about the competitive structure of the market. This apparently negative conclusion is an important warning against making over-generalized predictions about the effects of an advertising ban. Finally, the paper makes several proposals about how its hypothesis could be tested empirically.

A mechanism of cardiac pain suppression by spinal cord stimulation: implications for patients with angina pectoris.

Clinical reports show that electrical stimulation of the spinal cord reduces symptoms of angina pectoris, but so far have not provided evidence on the mechanisms involved. The hypothesis for this study was that inhibition of spinothalamic tract transmission may account for this result. Extracellular potentials of 28 spinothalamic tract neurons were recorded in anaesthetized monkeys, and the effects of dorsal column stimulation were determined on activity evoked by cardiac and somatic stimuli. Dorsal column stimulation reduced the number of cell potentials evoked by electrical stimulation of cardiopulmonary sympathetic afferent fibres in 11 spinothalamic tract cells tested. Activity evoked by intracardiac injection of bradykinin was decreased by dorsal column stimulation in six of seven neurons that responded to chemical stimulation of afferents. Differential effects of dorsal column stimulation were correlated to the cell responses to somatic field stimulation. Dorsal column stimulation inhibited activity in 12 of 12 neurons which were excited only by noxious pinch of somatic fields, whereas eight of 16 neurons which were excited by innocuous brushing of somatic fields were unaffected or excited. Transection of the dorsal column showed that the pathway transmitting inhibitory impulses descended from the stimulation site to the spinothalamic tract neurons examined. Results of this study are consistent with the concept that spinal cord stimulation reduces pain by decreasing the firing of spinothalamic tract cells which are activated by small fibre afferents. The paresthesias associated with nerve stimulation techniques may result from activation of spinothalamic tract cells which are excited by large fibre afferents. The clinical decision to employ spinal cord stimulation in patients with angina should balance the obvious benefit of pain relief against the risk of depriving the patient of an important warning signal while active myocardial ischaemia is in progress.