Testing Critical Slowing Down as a Bifurcation Indicator in a Low-Dissipation Dynamical System.

We study a two-dimensional low-dissipation nonautonomous dynamical system, with a control parameter that is swept linearly in time across a transcritical bifurcation. We investigate the relaxation time of a perturbation applied to a variable of the system and we show that critical slowing down may occur at a parameter value well above the bifurcation point. We test experimentally the occurrence of critical slowing down by applying a perturbation to the accessible control parameter and we find that this perturbation leaves the system behavior unaltered, thus providing no useful information on the occurrence of critical slowing down. The theoretical analysis reveals the reasons why these tests fail in predicting an incoming bifurcation.

Global characteristics of childhood acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) comprises approximately 5-10% of childhood acute myeloid leukemia (AML) cases in the US. While variation in this percentage among other populations was noted previously, global patterns of childhood APL have not been thoroughly characterized. In this comprehensive review of childhood APL, we examined its geographic pattern and the potential contribution of environmental factors to observed variation. In 142 studies (spanning >60 countries) identified, variation was apparent-de novo APL represented from 2% (Switzerland) to >50% (Nicaragua) of childhood AML in different geographic regions. Because a limited number of previous studies addressed specific environmental exposures that potentially underlie childhood APL development, we gathered 28 childhood cases of therapy-related APL, which exemplified associations between prior exposures to chemotherapeutic drugs/radiation and APL diagnosis. Future population-based studies examining childhood APL patterns and the potential association with specific environmental exposures and other risk factors are needed.

Extreme events in chaotic lasers with modulated parameter.

We study a theoretical model describing a laser with a modulated parameter, concentrating on the appearance of extreme events, also called optical rogue pulses. It is shown that two conditions are required for the appearance of such events in this type of nonlinear system: the existence of generalized multi-stability and the collisions of chaotic attractors with unstable orbits in external crisis, expanding the attractor to visit new regions in phase space.

Polycyclic aromatic hydrocarbons in residential dust and risk of childhood acute lymphoblastic leukemia.

Several polycyclic aromatic hydrocarbons (PAHs) are known or probable human carcinogens. We evaluated the relationship between PAH exposure and risk of childhood acute lymphoblastic leukemia (ALL) using concentrations in residential dust as an exposure indicator. We conducted a population-based case-control study (251 ALL cases, 306 birth-certificate controls) in Northern and Central California from 2001 to 2007. We collected residential dust using a high volume small surface sampler (HVS3) (n=185 cases, 212 controls) or by sampling from participants' household vacuum cleaners (n=66 cases, 94 controls). We evaluated log-transformed concentrations of 9 individual PAHs, the summed PAHs, and the summed PAHs weighted by their carcinogenic potency (the toxic equivalence). We calculated odds ratios (ORs) and 95% confidence intervals (CI) using logistic regression adjusting for demographic characteristics and duration between diagnosis/reference date and dust collection. Among participants with HVS3 dust, risk of ALL was not associated with increasing concentration of any PAHs based on OR perln(ng/g). Among participants with vacuum dust, we observed positive associations between ALL risk and increasing concentrations of benzo[a]pyrene (OR perln[ng/g]=1.42, 95% CI=0.95, 2.12), dibenzo[a,h]anthracene (OR=1.98, 95% CI=1.11, 3.55), benzo[k]fluoranthene (OR=1.71, 95% CI=0.91, 3.22), indeno[1,2,3-cd]pyrene (OR=1.81, 95% CI=1.04, 3.16), and the toxic equivalence (OR=2.35, 95% CI=1.18, 4.69). The increased ALL risk among participants with vacuum dust suggests that PAH exposure may increase the risk of childhood ALL; however, reasons for the different results based on HVS3 dust samples deserve further study.

The aryl hydrocarbon receptor regulates focal adhesion sites through a non-genomic FAK/Src pathway.

The aryl hydrocarbon receptor (AhR) is commonly described as a transcription factor, which regulates xenobiotic-metabolizing enzymes. Recent studies have suggested that the binding of ligands to the AhR also activates the Src kinase. In this manuscript, we show that the AhR, through the activation of Src, activates focal adhesion kinase (FAK) and promotes integrin clustering. These effects contribute to cell migration. Further, we show that the activation of the AhR increases the interaction of FAK with the metastatic marker, HEF1/NEDD9/CAS-L, and the expression of several integrins. Xenobiotic exposure, thus, may contribute to novel cell-migratory programs.

[Radiosurgery of cerebral arteriovenous malformations: a prescription algorithm]. / Radiochirurgie des malformations artérioveineuses cérébrales : élaboration d'un algorithme de prescription.

PURPOSE: To study prognostic factors of obliteration and risk factors of brain radiation necrosis in order to propose an algorithm for radiosurgery prescription for cerebral arteriovenous malformations (cAVM). MATERIAL AND METHODS: One hundred and seventy-nine patients were analysed. Radiosurgery delivered 6 or 10 MV X-rays by arc therapy in 84% of cases, or by fixed field in 16% of cases using two different micro-multileaf collimators (micro-MLC). Follow-up consisted of screening radiation necrosis by MRI every 6 months, and assessing local control by arteriography every 2 years. Obliteration was defined as at least 95% reduction of cAVM volume. Cox proportional hazard model was used to evaluate the local control and the appearance of radiation necrosis over time. RESULTS: Local control rate was 82.7% with the mean follow-up of 3.1 years (0.5-11). Significant prognostic factors were: simple nidus (RR=2.8, p<0.0001), number of embolizations before radiosurgery below 4 (RR=2.9, p<0.0001), prescribed dose to the periphery of at least 18 Gy (RR=2, p=0.0002), nidus volume below8cm(3) (RR=1.9, p=0.0002), and number of table positions below six (RR=1.4, p=0.05). Radiation necrosis rate was 11.2% with a mean time to onset of 18 months. Significant predictive factors were: fixed field versus arc therapy (according to MLC RR=9.1, p<0.0001, and RR=15.1, p=0.01), age below 30 years (RR=2.5, p=0.04), depth of cAVM greater than or equal to 7 cm (RR=7.6, p=0.008), and volume of brain tissue covered by the 12 Gy isodose (V12 Gy) of at least 11 cm(3) (RR=7.8, p=0.05). CONCLUSION: A radiosurgery prescription algorithm taking into account the prescribed dose to the periphery (> or = 18 Gy) and reduction of V12 Gy was elaborated from these data.

Analysis of chaining structures in colloidal suspensions subjected to an electric field.

Structures formed by a colloidal suspension of silica particles in 4-methyl cyclohexanol have been analyzed in the presence of an electric field. The formation of chains of particles was detected using an elliptical mirror to collect scattered light and a nearly matched refractive index between particles and solvent. A numerical method has been developed to obtain the size distribution of chains and their kinetics of formation from the record of a two-dimensional map of scattered light. We have compared the experimental size distribution to the prediction of a statistical theory based on a minimization of the free energy of a gas of chains. This theory quite well reproduced the experimental results for small chains but overestimates the tail of the distribution at high field. A saturation of the average size of chains versus the electric field was observed experimentally instead of a continuous growth as would be expected from aggregation under dipolar forces. A kinetic model, taking into account both capture and escape rates of a particle at the extremity of a chain, was shown to reproduce well the experimental growth of the average size of chains with time.

Parental social contact in the work place and the risk of childhood acute lymphoblastic leukaemia.

To study the possible relation between parental social contact through occupation, a marker for a child's risk of infection, and childhood acute lymphoblastic leukaemia (ALL), the parents of 294 children with ALL aged 0-14.9 years and 376 matched controls were interviewed about their jobs after their child's birth up to the age of 3 years. Job titles were assigned to a level of social contact, and an index of occupational social contact months was created using the level and the job duration. Positive interactions between this index and rural residence associated with an increased risk of childhood ALL and common ALL (c-ALL) were observed (interaction P-value=0.02 for both, using tertiles of contact months; interaction P-value=0.05 and 0.02 for ALL and c-ALL, respectively, using continuous contact months); such findings were not observed when job durations were ignored. Our data suggest that duration of parental occupation may be important when examining the association between parental social contact in the workplace and childhood leukaemia.

Proteomic analysis of childhood leukemia.

Childhood acute lymphoblastic and myeloid leukemias are stratified into molecular and cytogenetic subgroups important for prognosis and therapy. Studies have shown that gene expression profiles can discriminate between leukemia subtypes. Thus, proteome analysis similarly holds the potential for characterizing different subtypes of childhood leukemia. We used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to analyze cell lysates from childhood leukemia cell lines as well as pretreatment leukemic bone marrow derived from childhood leukemia cases. Comparison of the acute myeloid leukemia (AML) cell line, Kasumi, and the biphenotypic myelomonocytic cell line, MV4;11, with the acute lymphoblastic leukemia (ALL) cell lines, 697 and REH, revealed many differentially expressed proteins. In particular, one 8.3 kDa protein has been identified as a C-terminal truncated ubiquitin. Analysis of childhood leukemia bone marrow showed differentially expressed proteins between AML and ALL, including a similar peak at 8.3 kDa, as well as several proteins that differentiate between the ALL t(12;21) and hyperdiploid subtypes. These results demonstrate the potential for proteome analysis to distinguish between various forms of childhood leukemia. Future analyses are warranted to validate these findings and to investigate the role of the C-terminal truncated ubiquitin in the etiology of ALL.

Breastfeeding patterns and risk of childhood acute lymphoblastic leukaemia.

The risk of childhood acute lymphoblastic leukaemia (ALL) was investigated in relation to breastfeeding patterns in the Northern California Childhood Leukaemia Study. Data collected by self-administered and in-person questionnaires from biological mothers of leukaemia cases (age 0-14 years) in the period 1995-2002 were matched to birth certificate controls on date of birth, sex, Hispanic ethnic status, and maternal race. Ever compared to never breastfeeding was not associated with risk of ALL at ages 1-14 years (odds ratio=0.99; 95% CI=0.64-1.55) and ages 2-5 years (OR=1.49; 95% CI=0.83-2.65). Various measures of breastfeeding duration compared to absence of breastfeeding also had no significant effect on risk. Complimentary feeding characteristics such as type of milk/formula used and age started eating solid foods among breastfed children were not associated with ALL risk. This study provides no evidence that breastfeeding affects the occurrence of childhood ALL.

RAS mutation is associated with hyperdiploidy and parental characteristics in pediatric acute lymphoblastic leukemia.

We explored the relationship of RAS gene mutations with epidemiologic and cytogenetic factors in a case series of children with leukemia. Diagnostic bone marrow samples from 191 incident leukemia cases from the Northern California Childhood Leukemia Study were typed for NRAS and KRAS codon 12 and 13 mutations. A total of 38 cases (20%) harbored RAS mutations. Among the 142 B-cell acute lymphoblastic leukemia (ALL) cases, RAS mutations were more common among Hispanic children (P=0.11) or children born to mothers <30 years (P=0.007). Those with hyperdiploidy at diagnosis (>50 chromosomes) had the highest rates of RAS mutation (P=0.02). A multivariable model confirmed the significant associations between RAS mutation and both maternal age and hyperdiploidy. Interestingly, smoking of the father in the 3 months prior to pregnancy was reported less frequently among hyperdiploid leukemia patients than among those without hyperdiploidy (P=0.02). The data suggest that RAS and high hyperdiploidy may be cooperative genetic events to produce the leukemia subtype; and furthermore, that maternal age and paternal preconception smoking or other factors associated with these parameters are critical in the etiology of subtypes of childhood leukemia.

Previous pulmonary diseases and risk of lung cancer in Gansu Province, China.

BACKGROUND: Although active smoking is well established as the main cause of lung cancer, there is accumulating evidence that history of prior lung diseases may be an independent risk factor for lung cancer. METHODS: A population-based case-control study in Gansu Province, China identified 886 lung cancer cases (656 male, 230 female) diagnosed between January 1994 and April 1998. A standardized interview collected information on a variety of potential risk factors including a history of physician-diagnosed non-malignant lung diseases (pulmonary tuberculosis, chronic bronchitis/emphysema, asthma, pneumonia), age and year in which each condition was first diagnosed, and any therapy or hospitalization received. RESULTS: Pulmonary tuberculosis (odds ratio [OR] = 2.1, 95% CI : 1.4-3.1) and chronic bronchitis/emphysema (OR = 1.4, 95% CI : 1.1-1.8) were associated with increased risk of lung cancer, after adjustment for active smoking and socioeconomic status. The OR for asthma (OR = 1.4, 95% CI : 0.9-2.1) and pneumonia (OR = 1.5, 95% CI : 1.0-2.3) were also elevated. The risk of lung cancer remained significant for pulmonary tuberculosis and chronic bronchitis/emphysema when analysis was limited to the pathologically confirmed cases and self-responders. CONCLUSIONS: This study provides additional evidence that previous pulmonary tuberculosis and chronic bronchitis/emphysema are causally related to lung cancer, although the precise mechanism is still unclear. The results for asthma and pneumonia, while suggestive of a positive association, did not reach the traditional level of statistical significance and should be interpreted with caution.

Lung cancer and indoor air pollution in rural china.

PURPOSE: Indoor air pollution has been linked with lung cancer in China. In contrast to previous studies conducted in urban areas with high levels of industrial pollution, we undertook a lung cancer case-control study in a rural area of China, where residents live in underground dwellings. We evaluated the effects of radon, wood and coal combustion, cooking oil fumes, and environmental tobacco smoke on lung cancer risk.METHODS: We enrolled 886 lung cancer cases (656 males, 230 females) diagnosed between 1994-98, aged 30-75 years and 1765 frequency matched population-based controls from two prefectures in Gansu Province in Northwestern China. We conducted interviews with subjects or next of kin on smoking, housing characteristics, fuel use and cooking practices. Year-long radon detectors were placed in current and former homes of subjects.RESULTS: Subjects primarily used coal (22%), wood (56%) or a combination of both (22%) for heating. Odds Ratios (OR) for lung cancer rose with increasing percent of time that coal was used to heat homes over the past 30 years (ORs = 1.00, 1.17, 1.35, 1.23 compared to wood only, adjusted to smoking, P for trend = 0.025). Among non-smoking females and males, the OR for ever exposed to environmental tobacco smoke was 1.19, 95% CI = 0.7-2.0 with a significant trend for increasing years of exposure. Fumes from cooking with rapeseed oil increased the risk of lung cancer (OR = 1.56, 95% CI = 1.0-2.5) among non-smoking women. Among these women, occasional and frequent eye and throat irritation during cooking appeared to be associated with increased risk of lung cancer (ORs = 1.00, 1.42, 2.28, p trend < 0.01), whereas, increasing level of smokiness during cooking did not appear to affect risk.CONCLUSIONS: There is a suggestion that coal used for heating, environmental tobacco smoke, and cooking oil fumes contribute to the risk of lung cancer in this rural area of China.

Lung cancer and environmental tobacco smoke in a non-industrial area of China.

We report results from a population-based case-control study of lung cancer and environmental tobacco smoke (ETS) among never-smokers conducted in 2 rural prefectures of China, including 200 female and 33 male lung cancer cases, and 407 female and 114 male controls, matched on age, sex and prefecture of current residence. The odds ratio (OR) for ever-exposed to ETS was 1.19 (95% CI 0.7-2.0), with a significant trend (p<0.05) with increasing exposure. ORs were 1.00, 1.04, 1.13 and 1.51 for non-exposed, <10, 10-19 and >/=20 pack-years of ETS exposure, respectively. Excess risks were limited to ETS exposures in childhood (

Nonfatal work-related inhalations: surveillance data from hospital emergency departments, 1995-1996.

BACKGROUND: Data from a stratified sample of hospital emergency rooms in the USA were used to describe nonfatal work-related inhalation injuries and illnesses during July 1995 to July 1996. METHODS: Information was abstracted from emergency room records by the Consumer Product Safety Commission (CPSC) as part of the National Electronic Injury Surveillance System (NEISS) for all work-related injuries and illnesses regardless of product involvement. RESULTS: There were an estimated 44,423 occupational inhalation cases nationwide, with an annual rate of 3.6 cases/10(4) workers/year. The rate for men (4.4 cases/10(4)) was greater than that observed for women (2.6 cases/10(4)), and the rates tended to decline with increasing age. An estimated 4.6% of the cases were hospitalized for further treatment. The highest rate by industry was 16.4 cases/10(4) for public administration (which included fire and police departments). Among non-firefighters, there were an estimated 6,470 cases nationwide in which respiratory symptoms or conditions were noted, which yielded an annual rate of 0.5 cases/10(4) (95% CI 0.3, 0.7). Chlorine compounds were a common agent for the cases with adverse respiratory outcomes. CONCLUSIONS: The NEISS data provide an efficient method to learn about the national frequency of work-related inhalation injuries and illnesses. The National Institute for Occupational Safety and Health (NIOSH) is exploring two ways to use these data: first, to routinely review the reports to conduct surveillance for work-related inhalation cases; and second, to consider working with CPSC to conduct follow-back interviews of selected cases in order to learn more about the circumstances of the exposure, prior training of the case, and outcome of the exposure. Am. J. Ind. Med. 38:140-148, 2000. Published 2000 Wiley-Liss, Inc.

Second cancers among long-term survivors of Hodgkin's disease diagnosed in childhood and adolescence.

PURPOSE: To quantify the risk of second cancers among long-term survivors of Hodgkin's disease (HD) diagnosed before 21 years of age and to explore sex-, age-, and site-related differences. PATIENTS AND METHODS: We analyzed data from 5,925 pediatric HD patients, including 2,646 10-year and 755 20-year survivors, who were reported to 16 population-based cancer registries in North America and Europe between 1935 and 1994. RESULTS: A total of 157 solid tumors (observed/expected ratio [O/E] = 7.0; 95% confidence interval [CI], 5.9 to 8.2.) and 26 acute leukemias (O/E = 27.4; 95% CI, 17.9 to 40. 2) were reported. Risk of solid tumors remained significantly increased among 20-year survivors (O/E = 6.6, observed [O] = 40, cumulative risk = 6.5%) and persisted for 25 years (O/E = 4.6, O = 15, cumulative risk = 11.7%). Temporal trends for cancers of thyroid, female breast, bone/connective tissue, stomach, and esophagus were consistent with the late effects of radiotherapy. Greater than 50-fold increased risks were observed for tumors of the thyroid and respiratory tract (one lung and one pleura) among children treated before age 10. At older ages (10 to 16 years), the largest number of second cancers occurred in the digestive tract (O/E = 19.3) and breast (O/E = 22.9). Risk of solid tumors increased with decreasing age at HD on a relative but not absolute scale. CONCLUSION: Children and adolescents treated for HD experience significantly increased risks of second cancers at various sites for 2 to 3 decades. Although our results reflect the late effects of past therapeutic modalities, they underscore the importance of lifelong follow-up of pediatric HD patients given early, more aggressive treatments.

Barriers to cardiac transplantation in idiopathic dilated cardiomyopathy: the Washington, DC, Dilated Cardiomyopathy Study.

Although cardiac transplantation offers prolonged survival and improved quality of life to patients with end-stage heart failure, many patients with idiopathic dilated cardiomyopathy do not undergo this procedure. Possible barriers to cardiac transplantation were examined among 138 patients with idiopathic dilated cardiomyopathy from five hospitals in Washington, DC. Patients underwent follow-up for approximately 5 years. The patients or a close family member were interviewed at baseline about socioeconomic factors and medical history. The patients or their next-of-kin were recontacted at 1-year intervals to determine patients' vital status and to obtain information about cardiac transplantation. Overall, the cumulative survival at 12 and 60 months was 75.8% and 37.3%, respectively. Only 3.6% (5 of 138) of the patients underwent cardiac transplantation, and 19 (13.8%) patients had been placed on a waiting list for a heart transplant. Black race and nonmarried status were inversely associated with cardiac transplantation. Factors associated with not having been placed on a waiting list included older age, lower income, and lack of private health insurance. Black race was found to be significantly, but inversely associated with cardiac transplantation while older age was inversely associated with having been placed on a waiting list after adjusting for sex, race, education, and private insurance. These findings suggest that black patients with idiopathic dilated cardiomyopathy are less likely to undergo cardiac transplantation.

Nested case-control study of tumors of the hemopoietic and lymphatic systems among workers in the meat industry.

Workers in the meat industry are exposed to viruses that cause leukemia and lymphoma in cattle and chickens, and also to carcinogenic chemical agents. This case-control study, nested in a cohort of members of a meatcutters' union in Baltimore, Maryland, investigated whether occupational exposures are associated with death from tumors of the hemopoietic and lymphatic systems. Cases of these tumors represent all deaths which occurred in the cohort between 1949 and 1980. Excess risks of tumors of the hemopoietic and lymphatic systems were observed throughout the meat industry, except in meatpacking plants. Slaughtering activities involving heavy exposure to oncogenic viruses were strongly associated with these tumors, especially with lymphomas. Thus, elevated risks were observed for butchers who killed animals (odds ratio (OR) = 5.3, 95% confidence interval (CI) 1.0-27.0); workers in chicken-slaughtering plants (OR = 3.3, 95% CI 0.8-13.1); and workers in cattle/sheep/pig abattoirs (OR = 2.8, 95% CI 0.8-9.5). Among supermarket workers, wrapping meat (mainly a female activity) was associated with increased risk of tumors of the hemopoietic and lymphatic systems (OR = 3.8, 95% CI 1.0-14.3), with the odds of both lymphomas and tumors of the myeloid stem cell being elevated. On the other hand, meatcutting in supermarkets (almost exclusively a male activity) was associated with multiple myeloma; the odds ratio for men was 18.0 (95% CI 1.6-207.5), with no myeloma cases being recorded in women. These associations persisted after limited control for exposures outside the industry that have also been observed to be associated with excess risk, such as exposure to pesticides, working/living on pig farms, and exposure to X-rays. The findings provide evidence that workers in the meat industry may be at elevated risk of tumors of the hemopoietic and lymphatic systems. Further studies with larger sample sizes are needed to identify more conclusively which exposures play an etiologic role in the occurrence of the different histologic types of these tumors.