A Review of Healthcare Failure Mode and Effects Analysis (HFMEA) in Radiotherapy.

This paper presents a review of risk analyses in radiotherapy (RT) processes carried out by using Healthcare Failure Mode Effect Analysis (HFMEA) methodology, a qualitative method that proactively identifies risks to patients and corrects medical errors before they occur. This literature review was performed to provide an overview of how to approach the development of HFMEA applications in modern RT procedures, comparing recently published research conducted to support proactive programs to identify risks. On the basis of the reviewed literature, the paper suggests HFMEA shortcomings that need to be addressed.

Risk assessment of component failure modes and human errors using a new FMECA approach: application in the safety analysis of HDR brachytherapy.

Failure mode, effects and criticality analysis (FMECA) is a safety technique extensively used in many different industrial fields to identify and prevent potential failures. In the application of traditional FMECA, the risk priority number (RPN) is determined to rank the failure modes; however, the method has been criticised for having several weaknesses. Moreover, it is unable to adequately deal with human errors or negligence. In this paper, a new versatile fuzzy rule-based assessment model is proposed to evaluate the RPN index to rank both component failure and human error. The proposed methodology is applied to potential radiological over-exposure of patients during high-dose-rate brachytherapy treatments. The critical analysis of the results can provide recommendations and suggestions regarding safety provisions for the equipment and procedures required to reduce the occurrence of accidental events.

Fuzzy risk analysis of a modern γ-ray industrial irradiator.

Fuzzy fault tree analyses were used to investigate accident scenarios that involve radiological exposure to operators working in industrial γ-ray irradiation facilities. The HEART method, a first generation human reliability analysis method, was used to evaluate the probability of adverse human error in these analyses. This technique was modified on the basis of fuzzy set theory to more directly take into account the uncertainties in the error-promoting factors on which the methodology is based. Moreover, with regard to some identified accident scenarios, fuzzy radiological exposure risk, expressed in terms of potential annual death, was evaluated. The calculated fuzzy risks for the examined plant were determined to be well below the reference risk suggested by International Commission on Radiological Protection.

Risk analysis using fuzzy set theory of the accidental exposure of medical staff during brachytherapy procedures.

Using fuzzy set theory, this paper presents results from risk analyses that explore potential exposure of medical operators working in a high dose rate brachytherapy irradiation plant. In these analyses, the HEART methodology, a first generation method for human reliability analysis, has been employed to evaluate the probability of human error. This technique has been modified on the basis of fuzzy set concepts to take into account, more directly, the uncertainties of the so-called error-promoting factors on which the method is based. Moreover, with regard to some identified accident scenarios, fuzzy potential dose was also evaluated to estimate the relevant risk. The results also provide some recommendations for procedures and safety equipment to reduce the occurrence of radiological exposure accidents.

Optical polarization based logic functions (XOR or XNOR) with nonlinear Gallium nitride nanoslab.

We present a scheme of XOR/XNOR logic gate, based on non phase-matched noncollinear second harmonic generation from a medium of suitable crystalline symmetry, Gallium nitride. The polarization of the noncollinear generated beam is a function of the polarization of both pump beams, thus we experimentally investigated all possible polarization combinations, evidencing that only some of them are allowed and that the nonlinear interaction of optical signals behaves as a polarization based XOR. The experimental results show the peculiarity of the nonlinear optical response associated with noncollinear excitation, and are explained using the expression for the effective second order optical nonlinearity in noncollinear scheme.

Mapping the nonlinear optical susceptibility by noncollinear second-harmonic generation.

We present a method, based on noncollinear second-harmonic generation, to evaluate the nonzero elements of the nonlinear optical susceptibility. At a fixed incidence angle, the generated signal is investigated by varying the polarization state of both fundamental beams. The resulting polarization charts allows us to verify if Kleinman's symmetry rules can be applied to a given material or to retrieve the absolute value of the nonlinear optical tensor terms, from a reference measurement. Experimental measurements obtained from gallium nitride layers are reported. The proposed method does not require an angular scan and thus is useful when the generated signal is strongly affected by sample rotation.

Overlap among neurocutaneous syndromes. Observations on encephalocraniocutaneous lipomatosis.

The authors report a case of encephalocraniocutaneous lipomatosis (ECCL) in a female infant. Clinical manifestations in this case showed significative overlap with another neurocutaneous syndrome, namely oculocerebrocutaneous (OCC) Delleman's syndrome. This may support the theory of somatic mosaicism. The patient underwent a cerebrospinal fluid (CSF) shunt procedure due to marked tetraventricular hydrocephalus that was not present at birth. The need for close and multidisciplinary follow-up of these patients is stressed.

Bluetongue surveillance in the Campania Region of Italy using a geographic information system to create risk maps.

The aim of the project was the implementation of a geographic information system (GIS) to study areas of the Campania Region that are potentially at risk for bluetongue (BT) infection. As a first step, environmental, meteorological and climatic features were surveyed to evaluate areas where Culicoides could be present. A risk map was developed and five zones with different risk levels were defined. Data from Culicoides trapping were surveyed to evaluate the capability of the risk map to predict presence/absence of vectors. Finally, data from 2002 BT surveillance (outbreaks and serologically positive sentinels [SPS]) were compared to the map. Captures of Culicoides, SPS and BT in areas the map indicated as a medium/high risk level, seem to confirm reliability of the produced map. However, very few C. imicola were captured in these medium/high risk areas.

The prevalence of various arrhythmias in normotensive and hypertensive elderly patients.

The prevalence of the most frequent arrhythmias was studied in a geriatric day hospital. Patients older than 65 years have been considered, of them 118 were normotensive and 56 hypertensive subjects. Comparison of the two groups revealed no statistically significant difference either in the frequency of occurrence or in the type of arrhythmias. Dividing the hypertensive patients in the Lown's classes, only those of class 3 or over displayed a considerably higher frequency of arrhythmias than the normotensive subjects. The results demonstrate the age-dependent increase of the prevalence of arrhythmias in general, and the increased occurrence of complex ventricular types in the hypertensive subjects.

Application of low-temperature glassy carbon films in solid-phase microextraction.

Low-temperature glassy carbon (LTGC) films were investigated as a sorbent coating for solid-phase microextraction because of its uniquely selective adsorptive characteristics. The selectivity of these coatings is primarily controlled by shape characteristics of the solute molecule and the final processing temperature used to form the LTGC, demonstrating unique adsorptive characteristics compared to commercial phases. The LTGC films were prepared by first coating porous silica particles with a diethylnyl oligomer precursor and then heat curing at temperatures between 300 and 1000 degrees C to form the LTGC. Then, using a sol-gel process, the LTGC-coated silica particles were immobilized onto stainless steel fibers and subsequently used for headspace and liquid extractions followed by GC-FID analysis. The selectivity of the LTGC is demonstrated by the extraction of a variety of aromatic hydrocarbons as well as the taste and odor contaminants geosmin, 2-methylisoborneol, and 2,4,6-trichloroanisole commonly found in water supplies. The data show that the LTGC coating has the highest affinity for molecules with the greatest cross-sectional surface area and polarizability and that this selective mechanism increases as a function of LTGC processing temperature.

Serum alpha-L-fucosidase activity and early detection of hepatocellular carcinoma: a prospective study of patients with cirrhosis.

BACKGROUND: Serum alpha-L-fucosidase activity is considered a marker of hepatocellular carcinoma. To the authors' knowledge, its clinical usefulness in the early detection of hepatocellular carcinoma in the follow-up of cirrhotic patients has not been reported previously. METHODS: The authors prospectively studied serum alpha-L-fucosidase activity, in addition to alpha-fetoprotein and ultrasonography, in a regular screening of 132 cirrhotic patients during an 8-year follow-up. RESULTS: At enrollment, 120 patients had low alpha-L-fucosidase activity (below the cutoff value) and 12 had high activity. All patients had serum alpha-fetoprotein levels below the cutoff value. During the follow-up, hepatocellular carcinoma was detected in 19 patients, 16 with alpha-L-fucosidase activity below the cutoff value at enrollment and 3 with activity above it. In 7 of those 16 patients with carcinoma and low enzyme activity, the enzyme activity showed a significant increase 6-9 months before there was ultrasonographic evidence of a focal lesion, and by the time of diagnosis it had risen above the cutoff value in all of them; in only 3 of the 7 patients was the increase in alpha-L-fucosidase activity associated with an increase in alpha-fetoprotein. In another 4 of the 19 patients with carcinoma, only alpha-fetoprotein increased. CONCLUSIONS: Serum alpha-L-fucosidase activity is useful in the early detection of hepatocellular carcinoma. The data from this study suggest that cirrhotic patients who have a marked increase in serum alpha-L-fucosidase levels during follow-up should be closely monitored for signs of hepatocellular carcinoma development.

The effects of caloric restriction and controlled physical exercise on hypertension in the elderly.

The overweight and sedentary life style are associated with elevated blood pressure values in the elderly patients. The first step in the therapy of arterial hypertension should be hygienic-behavioral measures in order to modify the life style of the patients. The present study evaluates the independent effects of caloric restriction and physical exercise on the blood pressure and on the anti-hypertensive treatment in elderly subjects with mild-moderate hypertension. The number of enrolled patients was 74 in the age range of 61-72 years, showing up in our Geriatric Day Hospital. The results obtained confirm that the non-pharmacological measures represent a valid alternative to the pharmacological treatment of hypertension in the elderly patients, or may be applied in combination with the latter, in order to reduce the doses of pharmaca.

Kinetic analysis of glycogen synthase and PDC in cirrhotic rat liver and skeletal muscle.

Glycogen synthase (GS) and pyruvate dehydrogenase complex (PDC) were kinetically analyzed in the liver and skeletal muscle of fasted and refed rats with thioacetamide-induced cirrhosis of the liver. In control rats, refeeding induced a 54% decrease in the A0.5 for glucose 6-phosphate (G-6-P) of hepatic GS (P < 0.001), reflecting allosteric activation of the enzyme. In skeletal muscle the A0.5 for G-6-P did not change after refeeding, whereas the activity ratio increased by 56% (P < 0.01), indicating a greater percentage of the active G-6-P-independent form of the enzyme. In cirrhotic rats, neither the A0.5 for G-6-P of liver GS nor the activity ratio of muscle GS was influenced by refeeding. Consequently, glycogen replenishment was significantly impaired both in the liver (2.56 +/- 0.2 vs. 5.11 +/- 0.4 g/100 g; P < 0.001) and skeletal muscle (0.45 +/- 0.01 vs. 0.52 +/- 0.02 g/100 g; P < 0.01). Refeeding increased the percentage of the active form of hepatic PDC both in control (+88%; P < 0.01) and cirrhotic rats (+91%; P < 0.001). In the latter, however, the rates of total and active PDC were significantly lower than in controls [-44% and -40% in fasted (P < 0.005) and refed (P < 0.005) rats, respectively]. Muscle PDC kinetics (both maximal velocity and Michaelis constant) and the percent active form were identical in cirrhotic and control rats, regardless of the nutritional state.(ABSTRACT TRUNCATED AT 250 WORDS)

Chlorsulfuron resistance in Daucus carota cell lines and plants:Involvement of gene amplification.

Daucus carota L. cell lines stably resistant to the herbicide chlorsulfuron (CS) have been isolated according to a stepwise selection. Studies carried out during different selection steps show that the specific activity of the target enzyme acetohydroxyacid synthase (AHAS) increases along with CS resistance. Southern hybridization analysis performed with aBrassica napus AHAS probe in a CS highly-resistant cell line reveals the presence of a greatly amplifiedEcoRI fragment of genomic DNA. This indicates that AHAS overproduction induced by stepwise selection is due to gene amplification. Regenerants from some resistant cell lines maintained the CS-resistant trait at the whole plant level.

Renal cell (Grawitz) carcinoma: an immunohistochemical study in correlation with nuclear grade, histological pattern and proliferative activity of tumor cells.

Since morphological features of renal cell carcinomas may not always predict their clinical behaviour, other biological parameters are more and more searched for, as prognostic indicators. Among those, the Authors evaluate the cytokeratin-vimentin intermediate-sized filaments co-expression in a series of 32 renal carcinomas and analyze this feature in correlation with both traditional criteria and proliferative activity of tumor cells, studied by means of the proliferation cellular nuclear antigen (PCNA) expression as well as of the nucleolar organizer regions (NORs) count, within tumor cells. From this study, nuclear grade stands out as the best parameter which, furthermore, shows a significant relationship with the cytokeratin-vimentin co-expression and the mean NORs count in tumor cell populations. Further investigations about relationships between these parameters and survival of the patients, who, at present, are almost all alive, will be performed afterwards.

Serum alpha-L-fucosidase. A useful marker in the diagnosis of hepatocellular carcinoma.

BACKGROUND AND METHODS: The value of serum alpha-L-fucosidase activity in the diagnosis of hepatocellular carcinoma (HCC) was investigated by determining the enzyme activity levels in 21 patients with HCC, 76 patients with cirrhosis, 22 patients with other malignant neoplasms, and 23 healthy subjects. RESULTS: The serum alpha-L-fucosidase activity level in patients with HCC (575.76 +/- 212.86 nmol/ml/h) was significantly higher than that found in patients with cirrhosis (274.55 +/- 138.97 nmol/ml/h; P less than 0.001) or other neoplasms (257.91 +/- 128.12 nmol/ml/h; P less than 0.001) and in controls (221.23 +/- 114.45 nmol/ml/h; P less than 0.001). No significant differences were found between controls and patients with cirrhosis and between controls and patients with other malignant neoplasms. When 443 nmol/ml/h is taken as the cutoff value (mean value of controls plus 2 standard deviations), alpha-L-fucosidase sensitivity and specificity were 76% and 90.9%, respectively. CONCLUSIONS: These results suggest that alpha-L-fucosidase is a useful marker for detecting HCC, in conjunction with alpha-fetoprotein and ultrasonography.

Epileptic patients refractory to drug therapy.

We compared two groups of patients with idiopathic epilepsy, 41 patients whose seizure frequency was not controlled by adequate therapy and 39 patients in good seizure control, in respect of hematology, kidney and liver function tests, serum IgG, IgA and IgM concentrations and drug concentrations. The only difference that emerged were in the serum immunoglobulins, which were raised in the drug refractory group, significantly (p less than 0.01) so in the case of IgG. Failure of seizure control did not depend on inadequacy of drug dose or of blood concentration. Although the serum Ig changes do not warrant the assumption of an immunological origin for drug resistance, they do suggest a useful research line.

Longer-term regulation of pyruvate dehydrogenase kinase in cultured rat hepatocytes.

The activities of pyruvate dehydrogenase (PDH) kinase and of PDH kinase activator protein (KAP) were increased 2-2.4-fold during 25 h of culture of hepatocytes from fed rats with glucagon plus n-octanoate. PDH kinase activity in hepatocytes from starved rats (initially 2.2 x fed control) fell during 25 h of culture in medium 199 (to 1.5 x fed control), but was maintained by glucagon plus octanoate. Dibutyryl or 8-bromo cyclic AMP increased PDH kinase activity 2-2.2-fold in hepatocytes from fed rats, but phenylephrine and isoproterenol (isoprenaline) were without effect. Insulin blocked the action of glucagon to increase PDH kinase activity and decreased the effect of octanoate and octanoate plus glucagon. It is suggested that the effects of starvation to increase activities of PDH kinase and of KAP in liver are mediated by alterations in circulating concentrations of glucagon, fatty acids and insulin and in hepatic cyclic AMP.