Modelling chase-and-run migration in heterogeneous populations.

Cell migration is crucial for many physiological and pathological processes. During embryogenesis, neural crest cells undergo coordinated epithelial to mesenchymal transformations and migrate towards various forming organs. Here we develop a computational model to understand how mutual interactions between migrating neural crest cells (NCs) and the surrounding population of placode cells (PCs) generate coordinated migration. According to experimental findings, we implement a minimal set of hypotheses, based on a coupling between chemotactic movement of NCs in response to a placode-secreted chemoattractant (Sdf1) and repulsion induced from contact inhibition of locomotion (CIL), triggered by heterotypic NC-PC contacts. This basic set of assumptions is able to semi-quantitatively recapitulate experimental observations of the characteristic multispecies phenomenon of "chase-and-run", where the colony of NCs chases an evasive PC aggregate. The model further reproduces a number of in vitro manipulations, including full or partial disruption of NC chemotactic migration and selected mechanisms coordinating the CIL phenomenon. Finally, we provide various predictions based on altering other key components of the model mechanisms.

Coherent modelling switch between pointwise and distributed representations of cell aggregates.

Biological systems are typically formed by different cell phenotypes, characterized by specific biophysical properties and behaviors. Moreover, cells are able to undergo differentiation or phenotypic transitions upon internal or external stimuli. In order to take these phenomena into account, we here propose a modelling framework in which cells can be described either as pointwise/concentrated particles or as distributed masses, according to their biological determinants. A set of suitable rules then defines a coherent procedure to switch between the two mathematical representations. The theoretical environment describing cell transition is then enriched by including cell migratory dynamics and duplication/apoptotic processes, as well as the kinetics of selected diffusing chemicals influencing the system evolution. Finally, biologically relevant numerical realizations are presented: in particular, they deal with the growth of a tumor spheroid and with the initial differentiation stages of the formation of the zebrafish posterior lateral line. Both phenomena mainly rely on cell phenotypic transition and differentiated behaviour, thereby constituting biological systems particularly suitable to assess the advantages of the proposed model.

[The occupational health physician and the health surveillance in agriculture]. / Il medico del Lavoro Competente e la Sorveglianza Sanitaria in Agricoltura.

Despite the underreporting of occupational diseases in agriculture, available data clearly show a significant health risk, and therefore the need of health surveillance at the workplace. The implementation of health surveillance programs for agricultural workers relies on the possibility of creating a system able to reach the workers at their workplaces, with the collaboration of employers' associations, able to support enterprises in several issues, including risk assessment and management. The health surveillance program can be organized in a component common for all workers, based on physical examination, chemistry, electrocardiography, hearing and lung functions examinations, and on tests addressing specific risks, if present: vibration, physical overload, chemicals, biological agents, allergens. The frequency of examinations must be decided based on risk assessment and health surveillance outcomes.

[Biological risk prevention in agriculture and animal breeding: immunization strategies]. / Strategie vaccinali per la prevenzione del rischio biologico in agricoltura e zootecnia.

Vaccine preventable diseases are, so far, a main focus of Public Health programmes all over the world since people still die in consequence of Dyphteria or Tetanus. Biological risk is widely represented in agriculture and animal breeding, due to environmental characteristics and to injury typology. Moreover, aged people and migrants represent a significant part of the workforce. These two groups are, for instance, more exposed to Clostridium tetani infection because not fully immunized. Among infectious diseases that can affect agricultural workers, just tetanus can be well controlled by immunization programmes. Teaching and training activities are the most important tools to get protection against Leptospira interrogans, Salmonella spp and hepatitis E Virus infection. As for every training activity, linguistic and cultural barriers have to be taken into account.

[Workers with alcohol and drug addiction problems. Consensus Document of the Study Group on Hazardous Workers]. / Lavoratori con problemi di alcol e dipendenze. Documento di Consenso del gruppo La.R.A. (Lavoratori Rischiosi per gli Altri).

BACKGROUND: Italian Law 81/08 (so-called "Unified Text of Laws on Health and Safety at Work"), came into force on 15 May 2008 and incorporates provisions related to medical surveillance of drug and alcohol dependency at the workplace. OBJECTIVES: Occupational health traditionally addresses the issue of protection of worker from occupational hazards. The issue of protection of third parties from behaviour of workers resulting from drug and alcohol dependency implies an original methodological approach, involving full cooperation of employer, employees, and health and safety consultants. METHODS: A consensus development meeting was organized under the leadership of the Italian Study Group on Hazardous Workers (La.R.A. group). The meeting brought together physicians of different specialties, legal experts and bioethicists, labour and management policy-makers, to discuss the issue and define the research data available, the standards that were appropriate, and which policies were fair. RESULTS: The efficacy of medical surveillance, including workplace drug-testing, relies on a comprehensive policy, including written and verbal information on the use of alcohol and drugs on the job, training for supervisors and management, employee education, and employee assistance structures. Sample collection and testing should be carried out in accordance with standardized and tested procedures. Small businesses will need assistance, including development of model policies, setting up consortia for testing services and if necessary request for National Insurance benefits to reduce costs. CONCLUSIONS: The recently introduced Italian legislation on occupational safety and health closely resembles Finnish law since it consists of a "double channel" for workplace drug testing. At recruitment, the employer is entitled to ask a job applicant for a certificate of "Job fitness", including drug tests, that can be issued only by a public health institution, where the job applicant works on a well-defined set of tasks which require accuracy, trustworthiness, independent judgement or a very good reaction capacity. The employer may also refer the employee to the public health institution to obtain a certificate in the course of an employment contract when there is a legitimate suspicion that the employee is working while under the effects of drugs or alcohol or that the employee is a drug addict. After recruitment, the physician responsible for medical surveillance of workers (the so-called "Competent Physician") is entitled to perform drug tests on employees. The need for a test is decided by the health care professional, not by the employer, and only a general report on the health of the employee ("fit", fit with restrictions" or "unfit") may be given to the employer. Workers positive for drug tests will be referred to a public health institution for re-testing and treatment.

[The impact of personal protective equipment in reducing risk for operators exposed to pesticides: from theory to practice]. / La stima dell'impatto dei dispositivi di protezione nella riduzione del rischio in ambito di regolamentazione dei prodotti fitosanitari: dalla teoria alla pratica.

In Europe, the use of plant protection products is authorized provided the operator risk assessment carried out does not show exposure levels above the health-based triggers. Two models are currently available (German and UK models) to estimate exposure levels of agricultural operators. They consider, among different variables, the use of Personal Protective Equipment (PPE), based on their capacity to reduce exposure through the application of specific "reduction factors", derived from laboratory or field studies. Such factors, which date back to '90s, could be obsolete, as indicated by recent literature, posing problems on the reliability of current estimates. Therefore, the exposure estimates produced in Europe from 2005 to 2007, for 52 active ingredients in 395 scenarios, have been collected and analysed to check whether the application of recent exposure reduction factors might have an impact on the final outcomes. In some case the exposure levels resulted underestimated, highlighting the problem of operator safety with regard to the use of specific PPE and to an adequate training programme.

[Occupational and environmental exposure to anilide and dicarboximide pesticides]. / Esposizione ambientale e professionale a pesticidi propionanilidici e dicarbossimidici.

Dicarboximide fungicides (DF) such as vinclozolin, iprodione, procymidone are widely used on vines, fruit and vegetables, and anilide herbicides (AH) such as diuron, linuron, propanil are used to control weeds on hard surfaces, such as, roads, railway tracks, paths, and in crops, forestry. Italian reports on food safety found many samples contaminated by pesticides belonging to these categories, even though only few exceeding L.M.R. Since adverse effects on human health, such as endocrine disruption, have been reported, biological monitoring is essential for exposure assessment both of occupationally exposed subjects and of the general population. Common metabolites of DF and AH are dichloroanilinines such as 3,4-DCA and 3,5-DCA, urine samples from 153 subjects living in Novafeltria, central Italy, were collected for analysis of 3,4- and 3,5-DCAs, each participant was invited to complete a very detailed questionnaire. A total of 151 out of 153 samples were found to be positive for 3,5-DCA, and 81.7% were positive for 3,4-DCA. Also 33 workers, engaged in application of propanil on rice in northern Italy, were involved in the study and 3,4-DCA was determined as marker of exposure. 3,4 and 3,5 dichloroaniline are useful and promising biological indicators for monitoring occupational and environmental exposure to these classes of pesticides.

Modelling human perception processes in pedestrian dynamics: a hybrid approach.

In this paper, we present a hybrid mathematical model describing crowd dynamics. More specifically, our approach is based on the well-established Helbing-like discrete model, where each pedestrian is individually represented as a dimensionless point and set to move in order to reach a target destination, with deviations deriving from both physical and social forces. In particular, physical forces account for interpersonal collisions, whereas social components include the individual desire to remain sufficiently far from other walkers (the so-called territorial effect). In this respect, the repulsive behaviour of pedestrians is here set to be different from traditional Helbing-like methods, as it is assumed to be largely determined by how they perceive the presence and the position of neighbouring individuals, i.e. either objectively as pointwise/localized entities or subjectively as spatially distributed masses. The resulting modelling environment is then applied to specific scenarios, that first reproduce a real-world experiment, specifically designed to derive our model hypothesis. Sets of numerical realizations are also run to analyse in more details the pedestrian paths resulting from different types of perception of small groups of static individuals. Finally, analytical investigations formalize and validate from a mathematical point of view selected simulation outcomes.

[Occupational risk and prevention in the biotechnology industry: a review]. / Rischio professionale e prevenzione nell'industria biotecnologica: revisione della letteratura.

BACKGROUND: The biotechnology industry has expanded greatly in the last 20-30 years and has led to a number of applications in different sectors of work, i.e., medical and pharmaceutical, agricultural, chemical, energetic and others. Nowadays hundreds of thousands of workers worldwide are employed in biotechnology plants. Health and safety issues related to such working activities are considered as relevant to workers as well as to the general public. In particular, when compared to traditional biotechnology, modern methods of processing microrganisms have given rise to public concern that they might generate hazards to human beings and to the environment. OBJECTIVES AND METHODS: After summarizing the most important products and fields of application, the paper sets out to detail potential adverse effects for the health of biotechnology workers; in addition, an analysis of the literature highlights the various concepts of primary and secondary prevention. RESULTS AND CONCLUSION: Along with occupational risk factors common to other working activities (i.e. the well-known physical and chemical hazards), the peculiarity of handling microrganisms and/or different biologic systems may induce infections, immunological alterations or non-infective and non-immunologic toxic reactions in the workers involved The need is emphasized for an accurate risk assessment, careful control by means of the current monitoring strategies and implementation of the confinement measures, taking into account the criteria set by Italian legislation for occupational biological risk. Lastly, attention is focussed on examinations for the medical surveillance of workers at risk.

Influence of sex, age, and smoking habits on the urinary excretion of D-glucaric acid.

Reference values for urinary D-glucaric acid and the influence of sex, age and smoking habits were evaluated with a low-pH enzymatic method. D-Glucaric acid measured on spot urine samples from 573 healthy subjects gave mean concentrations (mumol/1) and D-glucaric acid/creatinine ratios (mmol/mol creatinine) of 56.1 (+/- 22.9) and 3.05 (+/- 0.99) for males and 53.3 (+/- 20.9) and 3.35 (+/- 0.95) for females. No difference between morning and evening was observed for urinary D-glucaric acid/1 values, but D-glucaric acid/creatinine was higher in the evening samples for both sexes. There was a negative correlation between D-glucaric acid/1 values and age in males but not in females: the decrease of D-glucaric acid concentration was, however, quantitatively very small. Smoking produced a significant increase in D-glucaric acid concentration and in the D-glucaric acid/creatinine ratio for males and also partially for females.

Low-pH method for the enzymatic assay of D-glucaric acid in urine.

The enzymatic methods for measuring D-glucaric acid in urine are based on the conversion of D-glucaric acid into its 1,4-lactone and measurement of inhibition of 1,4-lactone against beta-glucuronidase at pH 5.0. All the enzymatic methods described suffer from the disadvantage of a procedure that is complicated and inherently inaccurate, because the nature of glucaric acid/1,4-lactone equilibrium has not been properly considered in the development of such methods. After elucidating the factors influencing glucaric acid/1,4 lactone equilibrium in more detail, a low-pH enzymatic method has been developed in which the 1,4-lactone is formed in the urine sample by acid boiling at pH 3.8 and assayed at the same pH using beta-glucuronidase from Limpets. This procedure allows the acid/lactone equilibrium to remain stable during both the lactonization step and the enzymatic assay. The coefficient of variation for the proposed method (within-run and between-day precision) was from 4.2 to 8.7. The analytical recovery varied from 92-108%.

Determination of hexafluoroisopropanol, a sevoflurane urinary metabolite, by 9-fluorenylmethyl chloroformate derivatization.

A reversed-phase HPLC method with fluorescence detection for the quantification of hexafluoroisopropanol (HFIP) in urine is presented. HFIP, a metabolite of the inhalation anesthetic sevoflurane, is excreted mainly in urine as glucuronic acid conjugate. After enzymatic hydrolysis of the glucuronate, primary amino groups of interferent urinary compounds are blocked by reaction with o-phthalic dicarboxaldehyde and 3-mercaptopropionic acid, followed by labeling of HFIP with 9-fluorenylmethyl chloroformate. The derivatization reaction proceeds in a water-acetonitrile (1:1) solution at room temperature with a borate buffer of pH 12.5 as a catalyst. A stable fluorescent derivative of HFIP is formed within 5 min. The HFIP-FMOC derivative is separated by reversed-phase chromatography with isocratic elution on an octadecyl silyl column (33x4.6 mm, 3 microm) and guard column (20x4.0 mm, 40 microm), at 35 degrees C, and detected by fluorescence detection at an excitation wavelength of 265 nm and an emission wavelength of 311 nm. The method detection limit is 40 pg, per 10-microl injection volume, corresponding to 16 microg/l of HFIP in urine. The among-series relative standard deviation is <6% at 200 microg/l (n=6). As a preliminary application, the method was used to detect HFIP concentration in the urine of two volunteers exposed for 3 h to an airborne concentration of sevoflurane in the order of 2 ppm.

Biological and environmental monitoring of exposure to airborne benzene and other aromatic hydrocarbons in Milan traffic wardens.

Environmental and biological monitoring of airborne aromatic hydrocarbons has been performed in 20 policemen working as traffic wardens exposed to motor vehicle exhausts and in 19 peers employed as clerks. Airborne benzene, toluene, ethylbenzene and xylene concentrations, measured during the workshift, resulted in significantly higher outdoor than indoor concentrations (benzene and related aromatic hydrocarbons mean values, respectively of 53 and 350 micrograms/m3 vs. 29 and 180 micrograms/m3). Blood benzene, toluene, ethylbenzene and xylene concentrations did not differ significantly between indoor and outdoor workers; no differences were found between values obtained at the beginning (07:30 h) and the end of shift (00:30) in either group. Blood hydrocarbon concentrations seem to reflect airborne pollution, whilst the blood benzene concentration determined after the workshift poorly reflects airborne benzene morning peaks. Endshift blood benzene mean concentration in smokers (462 ng/l, n = 9) differs significantly from non-smokers (292 ng/l, n = 39).

Beta-2 microglobulin amyloidosis in a patient on long-term continuous ambulatory peritoneal dialysis (CAPD).

A 61-year-old female patient with ESRD due to analgesic nephropathy and treated solely with CAPD for 81 months is described. During this period she developed peritonitis 4 times. She eventually died of acute pulmonary edema due to coronary heart disease. The autopsy showed an analgesic nephropathy with contracted kidneys, diffuse peritoneal fibrosis, and articular and periarticular amyloidosis of AB2m-type. This form of amyloidosis is well known after hemodialysis; it was, however, not observed heretofore after sole long-term CAPD.

Transperitoneal calcium mass transfer using dialysate with a low calcium concentration (1.0 mM).

Lower dialysate calcium concentrations were recently proposed to overcome the risk of hypercalcemia in continuous ambulatory peritoneal dialysis (CAPD) patients on calcium-containing phosphate binders and/or vitamin D metabolites using the standard dialysate calcium concentration (SCa) of 1.75 mM. To assess transperitoneal calcium mass transfer (CaMT) in CAPD patients using a dialysate with a low calcium concentration (LCa, 1.00 mM), 18 stable patients were randomly allocated to receive either LCa or SCa. CaMT was assessed over 4 hours using 2L dialysate bags with three different dialysate glucose concentrations (1.5%, 2.3%, 4.25%). Total serum calcium (tCa), ionized calcium (iCa), and the exact dialysate volume were measured before and after the 4-hour dwell. A sample of the drained dialysate was obtained to measure the dialysate calcium concentration. The tCa and iCa levels were not significantly different in both groups prior to and did not change throughout the test. CaMT (median/range) was -0.64 mmol/exchange (-0.35(-)-1.29 mmol/exchange) using LCa with 1.5% glucose compared to 0.23 mmol (-0.18-0.87 mmol) with SCa (p < 0.0001). CaMT was negatively correlated to iCa and ultrafiltration volume [4.25%: LCa-1.22 (-0.84(-)-1.9); SCa -0.43 (-1.35-0.13); p < 0.001]. In summary, LCa results in a loss of calcium into the dialysate even at low ultrafiltration volumes and serum iCa levels. This might facilitate the prevention and therapy of renal osteodystrophy with calcium-containing phosphate binders and calcitriol. However, patients using LCa must be carefully monitored for calcium homeostasis and bone turnover.

Inaccuracy quality control in the monitoring of trace metal concentrations in biological fluids.

Quality assurance in trace element analysis requires continual surveillance of the accuracy and precision of results. A review of difficulties encountered in performing quality control programs of trace metal analysis in biological fluids is presented. Examples to clarify the inadequacy of available biological reference materials for quality control in biological monitoring of environmental and occupational low level exposure to metals are reported.

The speciation of the chemical forms of arsenic in the biological monitoring of exposure to inorganic arsenic.

Total As content may be determined in blood and urine by means of an AAS method that involves reduction of As to its volatile hydride and ashing at 600 degrees C with MgO and Mg (NO3)2. Separation of inorganic As (InAs), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMAA) by ion-exchange chromatography, followed by direct AAS analysis, allows the determination of each As species in the urine. In a reference population of 148 subjects with only normal environmental exposure to As, total As concentration in the urine averages 17.2 +/- 11.1 micrograms/l. Urinary As consists of 10% each of InAs, MMAA and DMAA, the remaining 70% consisting of other forms of organic As. Blood As concentration averages 5.1 +/- 6.9 micrograms/l and correlates significantly with the urinary concentration of InAs and the sum of its metabolites (InAs + MMAA + DMAA). Inorganic arsenic undergoes methylation in the organism. After ingestion of high quantities of As2O3, the time course of excretion of its metabolites indicates that As methylation occurs by a saturable mechanism. In workers exposed to As2O3, InAs, MMAA and DMAA are the only chemical forms of As excreted in the urine that are relevant to a study of occupational exposure. Blood As concentration is proportional to exposure and correlates only with urinary DMAA excretion; DMAA seems to be the most appropriate single indicator of exposure. At high levels of exposure (total As excretion above 200 micrograms/l), As accumulates in the organism and DMAA excretion reflects its accumulation. At low levels of exposure (total As excretion below 50 micrograms/l) a short-term accumulation does not occur and the best biological indicator of exposure is InAs excretion. Seafood ingestion brings about a marked increase in urinary excretion of total As that lasts for 24-48 h and is not accompanied by any increase in InAs, MMAA or DMAA excretion. Organic As from seafood does not mix with the pool of inorganic As in the organism and may be separately detected in urine. In the biological monitoring of human exposure to As, particularly in the case of high urinary values, the speciation of the chemical forms of As in urine is necessary in order to establish with certainty the source, industrial or alimentary, of exposure.

Viability of Ascaris suum, Ascaris lumbricoides and Trichuris muris eggs to alkaline pH and different temperatures.

Disposal of wastewater sludges in agricultural soil is a way to recover mineral and organic substances. Nevertheless disposing and handling such untreated, potentially contaminated sludges may be hazardous for human health and the environment. The aim of this study is to evaluate a method for sludge decontamination consisting in alkaline treatment with ammonia at different temperatures (22 degrees C, 30 degrees C, 40 degrees C) to establish its effects on the survival of Ascaris suum, Ascaris lumbricoides and Trichuris muris eggs. Our experiments show that the combination of alkalinization with NH4OH at a temperature of 30 degrees C causes the eggs to be inactivated. A 40 degrees C temperature was unfavourable to the development of these helminths in the eggs, with or without addition of NH4OH. At 22 degrees C ammonia did not have any effect on their viability. Ammonia at suitable temperatures therefore, is able to destroy Ascaris and Trichuris eggs. It is suggested that this technology be adopted to decontaminate wastewater sludge before using it as manure in agriculture.

Toxicological and immune findings in workers exposed to pentachlorophenol (PCP).

Pentachlorophenol (PCP) is a pesticide used worldwide in industrial and domestic applications. Data available on the effects of technical-grade PCP on the immune system are insufficient and equivocal; some data indicate inhibitory effects, whereas others suggest stimulating effects. This study was performed to evaluate toxicological and immune findings in 32 subjects who had prolonged exposure to PCP in a wood factory and in 37 controls. PCP concentrations were determined in plasma and urine of all subjects. Lymphocyte subsets of CD3-, CD4-, and CD8-positive cells were evaluated, and the proliferative response of peripheral blood mononuclear cells (PBM) to mitogens was assessed. The results suggested the absence of major laboratory and clinical signs of PCP-dependent immune deficiency. A weak effect of long-term exposure to PCP on the functional immune response could not be ruled out because of the finding of a decreased response to 5% PHA in the high-exposure group. A weak effect against hepatocyte membrane was evidenced by the finding of raised serum concentration of glycocholic, taurodeoxycholic, and glycochenodeoxycholic acids in subjects directly exposed to PCP for more than 10 y.

[Electrophysiology in neuropathy caused by vincristine]. / Estudio electrofisiólogico en la neuropatía por vincristina

Ten patients treated with vincristine were submitted for electrophysiological examination. It was investigated the number of motor units within the thenar muscle following a technique described previously (Sica et al. - 1974); motor and sensitive conduction velocities as well as motor distal latencies in the median nerve were studied following conventional techniques. The behaviour of the evoked muscle potential with repetitive supramaximal stimulation over the median nerve was also investigated. The findings were compared with control groups. The estimated number of motor units was disminished in eight of ten patients and the average number was significantly different from the control group (control 318 +/- 71 UM; patients 174 +/- 84 UM; P less than 0.001). The potential amplitudes in most of the surviving units were reduced, others remaining within the normal range. This makes apparent that the peripherical nervous system fails to compensate adequately and, furthermore, a loss of individual muscle fibres occurs within some individual units. The conduction velocities of the fastest conducting motor nerve fibres were reduced and motor distal latencies prolongued (Table 1). Maximal impulse conduction velocities were measured in sensory fibres. In 5 of 7 subjets investigated the values laied just beyond the lower limit of the normal range. The amplitude of the sensory orthodromic evoked potential in the median nerve at the wrist was disminished almost in the whole group. The decremental muscle response to repetitive nerve stimulation, can be interpreted as the result of the damage at the neural apparatus at the motor end plate; it was observed in 57% of the patients. In summary, evidences have been registered showing that the nervous supply to the muscle is affected in patients treated with vincristine; the motor unit behaviour under this conditions is discussed.