Arctic cut-off high drives the poleward shift of a new Greenland melting record.

Large-scale atmospheric circulation controls the mass and energy balance of the Greenland ice sheet through its impact on radiative budget, runoff and accumulation. Here, using reanalysis data and the outputs of a regional climate model, we show that the persistence of an exceptional atmospheric ridge, centred over the Arctic Ocean, was responsible for a poleward shift of runoff, albedo and surface temperature records over the Greenland during the summer of 2015. New records of monthly mean zonal winds at 500 hPa and of the maximum latitude of ridge peaks of the 5,700±50 m isohypse over the Arctic were associated with the formation and persistency of a cutoff high. The unprecedented (1948-2015) and sustained atmospheric conditions promoted enhanced runoff, increased the surface temperatures and decreased the albedo in northern Greenland, while inhibiting melting in the south, where new melting records were set over the past decade.

Mixture toxicity of S(N)2-reactive soft electrophiles: 2-evaluation of mixtures containing ethyl α-halogenated acetates.

Four ethyl α-halogenated acetates were tested in (1) sham and (2) nonsham combinations and (3) with a nonreactive nonpolar narcotic. Ethyl iodoacetate (EIAC), ethyl bromoacetate (EBAC), ethyl chloroacetate (ECAC), and ethyl fluoroacetate (EFAC), each considered to be an SN2-H-polar soft electrophile, were selected for testing based on their differences in electro(nucleo)philic reactivity and time-dependent toxicity (TDT). Agent reactivity was assessed using the model nucleophile glutathione, with EIAC and EBAC showing rapid reactivity, ECAC being less reactive, and EFAC lacking reactivity at ≤250 mM. The model nonpolar narcotic, 3-methyl-2-butanone (3M2B), was not reactive. Toxicity of the agents alone and in mixture was assessed using the Microtox acute toxicity test at three exposure durations: 15, 30 and 45 min. Two of the agents alone (EIAC and EBAC) had TDT values >100%. In contrast, ECAC (74 to 99%) and EFAC (9 to 12%) had partial TDT, whereas 3M2B completely lacked TDT (<0%). In mixture testing, sham combinations of each agent showed a combined effect consistent with predicted effects for dose-addition at each time point, as judged by EC(50) dose-addition quotient values. Mixture toxicity results for nonsham ethyl acetate combinations were variable, with some mixtures being inconsistent with the predicted effects for dose-addition and/or independence. The ethyl acetate-3M2B combinations were somewhat more toxic than predicted for dose-addition, a finding differing from that observed previously for α-halogenated acetonitriles with 3M2B.

Relating spatial heterogeneities to rotor formation in studying human ventricular fibrillation.

Ventricular fibrillation (VF) occurs due to disorganized electrical activity in the ventricles. This leads to rapid uncoordinated contractions of the ventricles and sudden cardiac death if not treated within minutes of its occurrence. The mechanism of VF initiation and maintenance is still elusive, however the mother rotor and multiple wavelet theories attempt to explain the mechanism behind this lethal arrhythmia. In mother rotor theory, VF is believed to be maintained by high frequency periodic sources called rotors that could be tracked using the phase progression along and through the myocardium using spatio-temporal electrical mapping of the heart. There are exiting works including our previous works that have related the formation of these rotors to anatomical and physiological heterogeneities observed in the myocardium. In this study we performed an correlation exercise of the locations of rotors with scar boundary maps and dominant frequency maps and elucidated this relation using human VF data acquired from isolated human hearts. The results suggest that in 14 rotors over 6 human hearts that we studied, all rotors co-localized to boundary zones of scar and low-high dominant frequency locations. The mean variance of the dominant frequency over the spatial location of the rotor was found to be 0.55 with average minimum of 4.15 Hz to a maximum of 5.71 Hz. This results in human VF data strongly suggest that boundary zones of healthy-non-healthy tissues and low-high frequency boundaries form a favorite substrate for rotor formation.

Mixture toxicity of SN2-reactive soft electrophiles: 1. Evaluation of mixtures containing α-halogenated acetonitriles.

The concept of multiple modes of toxic action denotes that an individual chemical can induce two or more toxic effects within the same series of concentrations, for example, reactive toxicity and narcosis. It appears that such toxicity confounds the ability to develop precise predictions of mixture toxicity and makes it more difficult to clearly link a dose-additive combined effect to agents in the mixture having a single common mechanism of toxic action. This initial study of a three-part series begins to examine this issue in greater detail by testing three α-halogenated acetonitriles: (1) in sham combinations, (2) in true combinations, and (3) with a nonreactive nonpolar narcotic. Iodo-, bromo-, and chloro-derivatives of acetonitrile were selected for testing based on their electro(nucleo)philic reactivity, via the S(N)2 mechanism, and their time-dependent toxicity individually. Reactivity of each agent was assessed in tests with the model nucleophile glutathione (GSH). Each acetonitrile was reactive with GSH, but the nonpolar narcotic 3-methyl-2-butanone was not. In addition, toxicity of the agents alone and in mixtures was assessed using the Microtox(®) acute toxicity test at three time points: 15, 30, and 45 min of exposure. Each of the three agents alone had time-dependent toxicity values of about 100%, making it likely that most of the toxicity of these agents, at these times, was due to reactivity. In contrast, the nonpolar narcotic agent lacked time-dependent toxicity. In mixture testing, sham combinations of each acetonitrile showed a combined effect consistent with predicted effects for dose-addition at each time point, as did the sham combination of the nonpolar narcotic. Mixture toxicity results for true acetonitrile combinations were also consistent with dose-addition, but the acetonitrile-nonpolar narcotic combinations were generally not consistent with either the dose-addition or independence models of combined effect. Based on current understanding of mixture toxicity, these results were expected and provide a foundation for the second and third studies in the series.

A South-East Asian perspective.

In order to discuss the subject of occupational medicine in the next century, changes in the present demographic profile and work activity must be considered first. Only then can the challenges be identified, and appropriate strategies be formulated to respond to them. In the diverse countries of South-East Asia, improved health and work conditions, the advent of new technology, a redistribution of work activity, and an ageing workforce can be expected. Two other factors that have specific impact in the region are the recent financial crisis and the occurrence of an international environmental haze from forest fires. The various countries in South-East Asia, which are in different stages of development, and have different problems and priorities, will respond differently to the demands for occupational health. It is likely that there will be a shift in the focus of current health care activities towards specific work sectors, the recognition of new hazards at work, the identification of newly emerging work related diseases, and an increase in health promotion in the workplace. Hopefully, there will be improved training of health professionals to ensure that there are adequate numbers and that they are well prepared to face these changes. Responsive, appropriate and well enforced labour legislation to protect the health of all workers, and international cooperation in occupational and environmental health are also required. As global and regional economic conditions continue to remain unstable and the impact of the crisis further takes its course, the final effect on occupational health in South-East Asia remains to be seen.

Collaboration between developing and developed countries and between developing countries in occupational health research and surveillance.

Collaborative occupational health and safety studies between counterparts in developing and developed countries and between developing countries have demonstrated their potential for improving occupational health and safety. Such collaboration in occupational health and safety is encouraged in the development of infrastructure in research empowerment and capacity building. This action includes the setting of priorities, the identification and documentation of problems, sponsorship, data bases and surveillance systems, technical support, methodology, publishing, research and training programs, controlled intervention, information exchange, and networking. Examples of priorities in occupational health and safety in the developing world include the informal sector (informally hired and independent workers), temporary work, pesticides, accidents, dusts, carcinogens, solvents, ergonomics, women and child labor, human immunodeficiency virus/acquired immunodeficiencey syndrome (HIV/AIDS), and transfer of hazardous materials and technologies. The sustainability of occupational health and safety structures and functions in the developing countries is a primary concern. Socioethical principles emphasize local, national, mutual and global gains. Examples of collaboration are given. Pervasive problems and strategies toward their solution are highlighted.

Occupational health in Singapore.

Singapore, a newly industrializing country in Southeast Asia, has a resident population of 3 million and a work force of 1.75 million. Most workers are employed in the manufacturing, services, and commerce sectors. Agricultural and mining activities are negligible. In 1996 the infant mortality rate was 3.8 per 1,000 live births and the life expectancy at birth was 77 years. In 1996 the total industrial accident rate was 2.7 per million man-hours worked and the severity rate was 353 industrial man-days lost per million man-hours worked. The shipbuilding and construction industries had the most frequent and most severe accidents. In the same year, 1,521 cases of occupational disease were notified to, and confirmed by, the Ministry of Labor. The majority of cases involved noise-induced hearing loss. There is substantial underreporting of cases. New cases that are expected to appear will be work-related illnesses such as musculoskeletal or psychosocial disorders. The principal occupational health legislation in Singapore is the Factories Act. Although it selectively targets workers at highest risk of developing occupational illness, its main limitation is the exclusion of nonfactory workers, who comprise 63% of the working population. Labor regulations are enforced by the Ministry of Labor. Workmen's compensation paid in 1995 amounted to S $46.6 million (U.S. $1=S $1.75). Education and training in occupational health is provided by employer federations, employee unions, and various government agencies. Occupational health is taught to medical students during their undergraduate training. Postgraduate-diploma and Masters programs in occupational medicine are also available. About 600 doctors in Singapore have some form of postgraduate training in occupational health. Health care for workers is offered either through the private sector or through government clinics and hospitals. Although Singapore has made great strides in protecting and promoting the health of its workers, it must constantly strive to strengthen its commitment to occupational health and safety. New problems in the next century must be anticipated and solutions, implemented. Improved training and development of health professionals is needed such that they be better prepared to deliver optimal occupational health care. Finally, labor legislation must be appropriate and responsive to protect the health of all workers.

Biomarkers, screening and ethics.

Rapid scientific advances, such as those in biomarker technology, have made a significant impact on the ethics and practice of occupational health. Biomarkers are extensively used in occupational health practice. In the pre-employment stage, preventive or predictive testing can be performed. Preventive testing aims to avert accidents that may occur if a medically unfit worker undertakes a job that he is unable to perform. For safety sensitive jobs, routine testing of a worker's functional capacity in the actual job would suffice in most cases. However, a recently quotes application of a test is the screening for mutations of the cardiac myosin-heavy chain and troponin genes among asymptomatic persons with a family history of sudden death from hypertrophic obstructive cardiomyopathy. Predictive testing hopes to forecast the risk of a worker developing an illness. The aims may vary. One aim may be to exclude a susceptible worker from working in a hazardous environment. Another aim may be to avoid employment of a worker who is likely to develop an illness which could lead to higher employer health care costs. A pertinent question to consider is whether the test undertaken is to benefit the individual or to fulfil some administrative or financial need. Among exposed workers, screening may be conducted for biomarkers of exposure or effect. As the aim is to prevent the onset of clinical illness, the physician must take responsibility for initiating requests for screening. The appropriate response to the effect of technical and societal advances on ethics is the updating of ethical guidelines by the profession. However, in the context of unvalidated biomarkers being used for screening, it may be necessary to require a regulatory body to ensure that the tests are accurate and effective, and that they are not used to discriminate against individuals.

Effects of occupational exposure to toluene: a neuropsychological study on workers in Singapore.

The neuropsychological functionings of workers (n = 29) occupationally exposed to low level of toluene (mean blood toluene level 1.25 ug/ml, standard deviation [SD] 0.37 ug/ml) were assessed by a test battery based on the recommendation of US National Institute of Occupational Safety and Health. The data revealed that the exposed workers performed poorer than a control group (mean blood toluene level 0.16 ug/ml, SD 0.06 ug/ml) in short-term memory, sustained attention and concentration, visual scanning, perceptual-motor speed, and finger dexterity. Results of the study confirmed that exposure to toluene may result in different degree of impairments of brain functions.

Menstrual patterns of workers exposed to low levels of 2-ethoxyethylacetate (EGEEA).

The objectives of this study were to determine the exposure levels among workers who handle 2-ethoxyethylacetate (EGEEA) in the liquid crystal display (LCD) manufacturing industry and to study the menstrual patterns among the exposed workers compared to a referent group of workers. A total of 52 female exposed workers and 55 referents was studied. Detailed menstrual histories were obtained by personal interview using a structured questionnaire. All the exposed had individual 8-hour personal monitoring for EGEEA in the environment and start-of-shift and end-of-shift urine analysis for EGEEA concentration. The geometric mean end-of-shift urine EGEEA concentration was 0.16 mg/g creatinine. End-of-shift urine EGEEA was well correlated with the air concentration; r = 0.81 [p < 0.0001]. No significant differences were observed between the exposed and referent groups for duration of each menstrual cycle (period), duration (days) of the menses, and the amount of flow, even after adjusting for possible confounders viz. age, years of education, use of oral contraceptive pills, age at menarche, gravidity, and race. The workers in the LCD manufacturing industry were exposed to a mean TWA of 0.51 ppm of EGEEA. At this concentration, the findings did not reveal any significant difference between the menstrual patterns of the exposed and referent subjects.

Cumulative blood lead levels and neurobehavioral test performance.

The current scientific literature provides inadequate evidence to conclude whether or not cumulative exposure to or absorption of lead adversely affects performance in neurobehavioral tests in adults. One of reasons for this controversy is the lack of studies with good cumulative exposure to or dose of lead. The aims of this study are to compare the neurobehavioral test performances of a group of lead-exposed workers and a referent group, and to study the association of the neurobehavioral test performances with concurrent blood lead levels and cumulative blood lead levels. Fifty lead battery workers and 97 non-exposed (referent) workers from a vehicle maintenance workshop were evaluated on their neurobehavioral performance using the World Health Organization Neurobehavioral Core Test Battery (WHO-NCTB). The geometric mean concurrent blood lead (ConPb) of the exposed and referent groups were 37.1 (range 13.2-64.6) microg/100 ml and 6.1 (range 2.4-12.4) microg/100 ml, respectively. Cumulative blood lead (CumPb) was defined as area under the curve for the number of years each worker was exposed to lead (three workers previous blood lead results were not available). ConPb and CumPb were used to study the association with the neurobehavioral test results. The exposed group had significantly poorer manual dexterity, perceptual-motor speed, and motor steadiness compared with the referents. The standardized partial regression coefficients were higher for CumPb than ConPb for most of the neurobehavioral test results. In the group >35 years old, there were significantly stronger associations between CumPb and Digit Symbol and Trail Making Part A results than for ConPb which are tests of perceptual and motor skills. CumPb was a better predictor than ConPb of the effects of lead on neurobehavioral performances.

Three-year follow-up of serial nerve conduction among lead-exposed workers.

OBJECTIVES: The purpose of this study was to investigate the serial nerve conduction parameters of a group of lead-exposed workers and determine their correlation with the serial blood lead results over a three-year period. A "nonresponse" level (defined as no significant changes in the nerve conduction in response to changes in the blood lead level of each exposed worker observed over the period of study) was also determined for blood lead in respect to the peripheral nerves. METHODS: Seventy-two male workers from a lead battery manufacturing factory were followed at six-month intervals for three years. At each follow-up, the blood lead level was determined and nerve conduction tests (ulnar and median nerves) were conducted. A group of 82 unexposed subjects served as referents. RESULTS: Significant differences were observed for some of the mean values of the median nerve conduction parameters between the exposed and reference groups. The 28 exposed workers who completed the follow-up were divided into the following two blood lead categories: < 40 micrograms. 100 ml-1 (< 1.93 micromol.l-1 and > or = 40 micrograms. 100 ml-1 (> or = 1.93 micromol.l-1. In the latter, the median motor conduction velocity, median distal latency, median amplitude, ulnar motor conduction velocity, and ulnar amplitude were significantly correlated (adjusted for age and within-subject variation) with the blood lead levels, but not so in the former. CONCLUSIONS: According to the three-year serial results, the "nonresponse" level for blood lead with respect to the peripheral nerves would be < 40 micrograms.100 ml-1 (< 1.93 micromol. l-1).

Cumulative concentrations of blood lead and postural stability.

OBJECTIVE: To study the association in a group of battery manufacturing workers between computerised postural sway parameters and present concentrations of blood lead (PPb), index of cumulative blood lead years (CBI), and cumulative blood lead at different years of exposure (CPbYs). METHODS: Postural stability was investigated with a computerised postural sway measurement system in 60 workers exposed to lead with exposure duration of 84 (range 3-366) months and in 60 control subjects. An index of CBIs in 55 workers (previous blood lead results of five workers were not available) and CPbYs were computed for each worker by calculating the area under the curve of concentrations of blood lead against time. RESULTS: The mean (SD) PPb was 36.0 (11.7) (range 6.4 to 64.5) micrograms/dl for the exposed workers and 6.3 (2.4) (range 3.1-10.9) micrograms/dl for the 14 randomly selected control subjects. Significant differences between groups for the postural sway parameters obtained when the eyes were closed were found for length of sway path (L); mean velocity of the centre of pressure along its path (Vel); area included within the path of the centre of pressure (Ao); 95% confidence elliptical area (Ae). The Romberg ratio (the relation between eyes closed and open) for the Vel, L, Ao, and Ae of the exposed group were also significantly different from those of the controls. The postural sway parameters (eyes closed) were not significantly correlated with PPb or CBI. However, the cumulative blood lead for the past two years before the postural sway assessment, CPbY2, was significantly correlated with all the postural sway parameters. CONCLUSION: The study showed that workers exposed to lead had significantly poorer postural stability than a control group. Lead may affect certain parts of the somatosensory system resulting in postural instability when the visual input is cut off. The CPbY2 was significantly positively correlated with most of the postural sway parameters. Effects of lead on postural stability may be related to recent increases in blood lead concentration among the exposed workers rather than to cumulative body burden.

Cumulative blood lead levels and nerve conduction parameters.

Most studies on the effects of lead on the peripheral nerves used "current' blood lead levels of the workers and infer the nerve conduction's findings to it. This practice is not ideal as the toxicity of lead on the peripheral nerves occurs over a period of time. Seventy-two workers in a lead battery manufacturing factory and 82 referents were studied with the aim of (1) correlating the nerve conduction parameters of the median and ulnar nerves of the dominant forearms with the blood cumulative lead-years (BPbCum) results; (2) determining a "noeffect' cumulative dose of lead on the peripheral nerves. The mean BPb for the exposed and referent were 36.9 micrograms/100ml and 10.5 micrograms/100ml, respectively. The mean BPbCum was 136.8 (range = 6.7-1087.0)micrograms-year/100ml. Significant differences were found in the adjusted (for age, ethnical groups, smoking and drinking habits by ANCOVA) means median sensory conduction velocity, motor conduction veloclty, distal latency and amplitude between the exposed and referent groups. But for the ulnar nerve only, distal latency was significantly different. With the BPbCum groups, dose response relations are noted in both the nerve conduction parameters of the median and ulnar nerves. There were no significant differences for the ulnar and median nerves conduction parameters between BPbCum < 40 micrograms-year/100ml group and referent. Based on the study's findings, it would suggest that a maintained blood lead level of less than 40micrograms/100ml for one year may not have significant effects on the median and ulnar nerves.

Lead-induced nephropathy: relationship between various biological exposure indices and early markers of nephrotoxicity.

Lead nephropathy in adults is silent and insidious, characterized by the absence of proteinuria in its early phase. Of the early markers of nephrotoxicity, urinary N-acetyl-beta-D-glucosaminidase (NAG) appears to be the only one that is elevated in early lead nephropathy. However, the elevation in urinary NAG activity may be a response to a sharp increase in renal burden of lead. Its usefulness as a marker of chronic lead nephropathy is thus in doubt. There is a need, then, to identify a reliable early biological indicator of lead-induced kidney damage. Furthermore, there is also a need to identify suitable markers of chronic exposure to describe meaningful dose-response and dose-effect relationships. Traditionally, blood lead (PbB) was used, but the current blood lead level (PbBrec) is more an indicator of recent exposure. Time-integrated blood lead indices (PbBint) derived from repeated serial PbB measurements can be used as indices of chronic exposure. In 128 lead-exposed workers, the PbBint was the most important exposure variable in describing the variability in urinary alpha 1-microglobulin (U alpha 1 m), urinary beta 2-microglobulin (U beta 2m), and urinary retinol binding protein (URBP). U alpha 1m was the only marker that was significantly higher in the exposed group, with a good dose-response and dose-effect relationship with PbBint. The lack of dose-response and dose-effect relationships in other studies may be due to inappropriate exposure markers as well as less sensitive response markers. PbBint has a better correlation than PbBrec. Furthermore, U alpha 1m may be the most sensitive of the markers because of its higher molecular weight.

Glomerular function of lead-exposed workers.

Among lead-exposed workers, there is evidence of increased mortality from chronic renal diseases (nephritis and nephrosis). Epidemiological studies using early markers of nephropathy among lead-exposed workers failed to demonstrate early renal changes. This study is aimed at assessing the glomerular function of 137 lead-exposed subjects and at evaluating whether changes in markers of glomerular function are related to exposure indices derived from longitudinal blood lead data. A control group of 153 postal workers was also investigated. Several exposure indices were derived for the exposed workers, including a time-integrated index Pb in blood (PbB)int and the number of times the PbB was above critical values (PbB400, PbB500, PbB600). Through multiple linear regression analysis, PbBint was the best predictor of variation in serum beta 2-microglobulin (S beta 2m) and alpha 1-microglobulin (S alpha 1m) and urinary albumin (UA1b). A small but statistically significant difference in the mean beta 2m was found. S beta 2m was also the only marker showing a significantly higher prevalence rate ratio (PRR) of abnormalities among lead-exposed workers. Though there was no clear dose-response relationship with PbBint as the index of dose, all the 15 subjects with abnormal S beta 2m in the older age group were found in the highest PbBint group. Furthermore, of the 8 subjects with low 4-h creatinine clearance (CrCl4h), 6 had abnormal levels of beta 2m. Two subjects with CrCl4h of less than 75 ml/min/1.74 m2 had high PbBint values, thus suggesting that high blood lead levels over a prolonged time may be associated with decreased CrCl4h. Though the long-term significance of elevated S beta 2m and UA1b is unclear, their association with high PbBint and decreasing CrCl4h indicate a potentially adverse effect. Their relationship with PbB400 and PbB600 suggests that the threshold of 700 micrograms/l for PbB may not prevent the occurrence of lead nephropathy.

Case studies in occupational medicine for medical undergraduate training.

Medical undergraduate tutorials in occupational medicine were introduced in 1993 in Singapore. The tutorials discuss three case studies of patients likely to be encountered in primary health care practice--occupational dermatitis, tinnitus in a noise-exposed worker, and the finding of anaemia in a pre-employment examination. The cases are used to illustrate the importance of identification of occupational factors in the causation of disease; consideration of occupational factors in the management of disease; and measures for prevention of occupational and work-related diseases and promotion of health at work. Staff and student responses to the case studies have been positive. All five staff members involved in the teaching enjoyed the experience, and over 90% of the 105 students who participated in the tutorial felt that the material was well prepared, the time was well spent, and that the tutorials had thrown new light on and overcome difficulties encountered during the course.