Additional Safety Margin Research Articles

Evaluation of Escherichia coli biotype 1 as a surrogate for Escherichia coli O157:H7 for cooking, fermentation, freezing, and refrigerated storage in meat processes.

Five Escherichia coli biotype I isolates were compared with E. coli O157:H7 under four common meat processing conditions. The processes that were evaluated were freezing, refrigerating, fermentation, and thermal inactivation. For each study, at least one surrogate organism was not statistically different when compared with E. coli O157:H7. However, the four studies did not consistently show the same isolate as having this agreement. The three studies that involved temperature as a method of controlling or reducing the E. coli population all had at least one possible surrogate in common. In the fermentation study, only one isolate (BAA-1429) showed no statistical difference when compared with E. coli O157:H7. However, the population reductions that were observed indicated the isolates BAA-1427 and BAA-1431 would overestimate the surviving E. coli O157:H7 population in a fermented summer sausage. When all of the data from all of the surrogates were examined, it was found that isolates BAA-1427, BAA-1429, and BAA-1430 would be good surrogates for all four of the processes that were examined in this study. There was no statistical difference noted between these three isolates and E. coli O157:H7 in the refrigeration study. These isolates resulted in smaller population reductions than did E. coli O157:H7 in the frozen, fermentation, and thermal inactivation studies. This would indicate that these isolates would overpredict the E. coli O157:H7 population in these three instances. This overprediction results in an additional margin of safety when using E. coli biotype 1 as a surrogate.

Exploiting bulk residual stresses to improve fatigue crack growth performance of structures

Bulk residual stress, normally viewed as a nuisance, requires additional safety margin and reduces structural performance. However, by carefully considering residual stress during the design and manufacturing processes, it should be possible to remove the uncertainty associated with residual stress and optimize the residual stress in a part for maximum performance. This analysis, design, and test program clearly demonstrates the potential for such improvement and a method to achieve it. An aluminum–lithium extrusion was selected, and its residual stress and crack growth properties were measured. A design study for center-cracked fatigue crack growth specimens was conducted with the specimen excise location within the extrusion cross-section as the design variable. The stress intensity factors due to residual stress were predicted with finite element analysis and incorporated into crack growth predictions by superposition. For validation, several specimens were produced and tested. Test results confirmed the analytical predictions, and the longest crack growth life was 3.7 times the shortest.

Potential of image-guidance, gating and real-time tracking to improve accuracy in pulmonary stereotactic body radiotherapy

Purpose To evaluate the potential of image-guidance, gating and real-time tumor tracking to improve accuracy in pulmonary stereotactic body radiotherapy (SBRT). Materials and methods Safety margins for compensation of inter- and intra-fractional uncertainties of the target position were calculated based on SBRT treatments of 43 patients with pre- and post-treatment cone-beam CT imaging. Safety margins for compensation of breathing motion were evaluated for 17 pulmonary tumors using respiratory correlated CT, model-based segmentation of 4D-CT images and voxel-based dose accumulation; the target in the mid-ventilation position was the reference. Results Because of large inter-fractional base-line shifts of the tumor, stereotactic patient positioning and image-guidance based on the bony anatomy required safety margins of 12 mm and 9 mm, respectively. Four-dimensional image-guidance targeting the tumor itself and intra-fractional tumor tracking reduced margins to <5 mm and <3 mm, respectively. Additional safety margins are required to compensate for breathing motion. A quadratic relationship between tumor motion and margins for motion compensation was observed: safety margins of 2.4 mm and 6 mm were calculated for compensation of 10 mm and 20 mm motion amplitudes in cranio–caudal direction, respectively. Conclusion Four-dimensional image-guidance with pre-treatment verification of the target position and online correction of errors reduced safety margins most effectively in pulmonary SBRT.

Avaliação da segurança de pilares mistos preenchidos de seção circular projetados segundo a norma NBR 8800:2008

Este artigo apresenta uma investigação da segurança de pilares mistos preenchidos de seção circular, dimensionados segundo a norma brasileira NBR 8800:2008. Esta investigação é feita com base na comparação de previsões normativas com a resistência obtida em 32 ensaios experimentais, bem como na comparação com as normas americana e européia correspondentes. O erro de modelo das equações teóricas de resistência destas normas é determinado. Uma análise de covariância é realizada para verificar tendências das equações de resistência. O estudo mostra que o modelo de resistência utilizado na norma brasileira é compatível com as normas estrangeiras, em termos de tendenciosidade e variância. O estudo revela uma margem de segurança adicional da ordem de 10% na NBR8800, quando removidos os coeficientes parciais de segurança. Uma análise de confiabilidade é realizada para 3888 configurações de pilar, resultando em índices de confiabilidade que refletem a segurança do universo de pilares cobertos pelas normas. O estudo mostra que a norma brasileira apresenta índices de confiabilidade compatíveis com as normas estrangeiras.

A novel application of high-dose (50 kGy) gamma irradiation for demineralized bone matrix: effects on fusion rate in a rat spinal fusion model

Background context The safety of allograft material has come under scrutiny because of recent reports of allograft-associated bacterial and viral infections in tissue recipients. Gamma irradiation, although being one of the most effective ways of terminal sterilization, has been shown to affect the biomechanical properties of allograft bone. It may also have detrimental effects on the osteoinductivity of allograft material such as demineralized bone matrix (DBM) by the denaturation of proteins because of heat generated by irradiation. Sterilization of DBM material is an important variable in processing graft materials. This is considered to be one of the factors leading to different fusion rates observed with different commercially available DBM products, as the sterilization procedure itself may affect the osteoinductivity of the material. Currently, there is no ideal sterilization technique that limits the detrimental effect on osteoinductivity and fusion rates. Purpose To evaluate the effects of a range of hydrogen peroxide exposures with or without the controlled high-dose gamma irradiation after processing with radioprotectant solutions (Clearant radiation sterilization procedure) on the fusion rates of human DBM. Study design A prospective in vivo animal study. Methods Eighty mature athymic nude female rats were used for this study, which formed 10 equal groups. Human DBM exposed to hydrogen peroxide for different time periods (0, 1, 6, and 24 hours) was divided into two major subgroups. One group was further treated with controlled high-dose radiation using radioprotectants (radiation treated), whereas the other group was frozen immediately without specific treatment (non-radiation treated). Both radiation-treated and non–radiation-treated DBM material from each group of hydrogen peroxide exposure times were implanted between L4 and L5 transverse processes of the rats forming eight test groups including eight animals in each. The remaining 16 rats were divided into two additional groups to form negative (only decortication, n=8) and positive (bone morphogenetic protein [BMP]-2, n=8) control groups. The rats were evaluated for fusion by radiographs (2, 4, and 8 weeks), manual palpation (8 weeks), and histological analysis after sacrificing. Comparison of fusion rate among all groups was made using these three evaluation methods. Results Increasing the time period of hydrogen peroxide (0, 1, 6, or 24 hours) exposure for preparation of DBM from bone allograft did not affect the fusion rates significantly (p<.05), although there was a trend toward decreasing fusion rates with longer exposure times. When the hydrogen peroxide washed DBM preparations were also radiation treated, the resulting fusion rates were again not significantly different (p<.05). Agreement among fusion detection methods was found to be high. Conclusions Hydrogen peroxide processing was not detrimental to fusion rates. The additional terminal sterilization technique with special gamma irradiation protocols (Clearant process) also did not decrease the fusion rates but could provide an additional margin of safety.

Improved safety margins for Belgian nuclear power plants by the application of the Master Curve approach to RPV surveillance materials

In the context of existing regulatory codes, the integrity assessment of the pressure vessel of a nuclear power plant (NPP) is based on the empirical assumption that the fracture toughness of the surveillance materials, expressed in terms of a lower bound curve indexed by a reference temperature RT NDT, undergoes a shift under irradiation by an amount equal to the increment of the T 41 J index temperature measured from surveillance Charpy tests. Nowadays, an alternative route exists, based on: reconstitution of previously tested specimens; execution of fracture toughness tests in the irradiated condition; Master Curve analysis of the results obtained and finally determination of an alternative toughness-based reference temperature ( RT T 0 ) , which can be used to index the lower bound K Ic curve. As we demonstrate in this paper for several surveillance materials extracted from Belgian power plants, this “advanced” approach can provide NPP owners and plant engineers an additional safety margin with respect to the operating limits of the reactor and the pressurized thermal shock (PTS) screening criteria. These additional safety margins have been found particularly significant for older plants, for which the actual fracture toughness in the unirradiated condition is often underestimated by the approach based on RT NDT.

ATWS Characteristics of Super LWR with/without Alternative Action

Anticipated-transient-without-scram (ATWS) of the supercritical-pressure light water cooled thermal reactor with downward-flow water rods (Super LWR) is analyzed to clarify its safety characteristics. At loss-of-flow, heat-up of the fuel cladding is mitigated by the water rods removing heat from the fuel channels by heat conduction and supplying their coolant inventory to the fuel channels by volume expansion. The average coolant density is not sensitive to the pressure due to the small density difference between “steam” and “water” at supercritical-pressure. Closure of the coolant outlet of the once-through system causes flow stagnation that suppresses an increase in the coolant density due to an increase in the temperature. Therefore, the increase in power is small for pressurization events. The coolant density and Doppler feedbacks provide good self-controllability of the power against loss-of-flow and reactivity insertion. An alternative action is not needed either to satisfy the safety criteria or to achieve a high-temperature stable condition for all ATWS events. Initiating the automatic depressurization system is a good alternative action that induces a strong core coolant flow and inserts a negative reactivity. It provides an additional safety margin for the ATWS events. Even the high core power rating of the Super LWR has excellent ATWS characteristics, providing a key reactor design advantage.

ATWS Characteristics of Super LWR with/without Alternative Action

Anticipated-transient-without-scram (ATWS) of the supercritical-pressure light water cooled thermal reactor with downward-flow water rods (Super LWR) is analyzed to clarify its safety characteristics. At loss-of-flow, heat-up of the fuel cladding is mitigated by the water rods removing heat from the fuel channels by heat conduction and supplying their coolant inventory to the fuel channels by volume expansion. The average coolant density is not sensitive to the pressure due to the small density difference between “steam” and “water” at supercritical-pressure. Closure of the coolant outlet of the once-through system causes flow stagnation that suppresses an increase in the coolant density due to an increase in the temperature. Therefore, the increase in power is small for pressurization events. The coolant density and Doppler feedbacks provide good self-controllability of the power against loss-of-flow and reactivity insertion. An alternative action is not needed either to satisfy the safety criteria or to achieve a high-temperature stable condition for all ATWS events. Initiating the automatic depressurization system is a good alternative action that induces a strong core coolant flow and inserts a negative reactivity. It provides an additional safety margin for the ATWS events. Even the high core power rating of the Super LWR has excellent ATWS characteristics, providing a key reactor design advantage.

Intraoperative Technique to Define the Safe Lateral Limits of Anterior Cervical Corpectomy

We describe a surgical radiographic technique during anterior cervical corpectomy to define the safe lateral limit of dissection. To assess the radiographic technique accuracy using computed tomography (CT) measurements on cadaveric specimens. Two clinical cases are presented. During anterior cervical surgery loss of orientation can lead to eccentric decompression and vertebral artery injury. A two-level corpectomy on 4 cadaveric samples was filled with radioopaque dye. An "introperative" antero-posterior x-ray was used to measure the narrowest distance from dye column to uncovertebral joints. A CT scan confirmed the distance from corpectomy to vertebral arteries. The distance between the x-ray dye column and uncovertebral joints averaged 2.7 mm (range, 0 to 7+/-2.2 mm). A CT scan demonstrated the distance from corpectomy to vertebral artery averaged 4.5 mm (range, 0 to 10+/-4.4 mm). The measured distance underestimated the true distance by an average of 1.8 mm (range, 0 to 8+/-2.2 mm). An intraoperative radiographic technique can estimate the lateral distance between the corpectomy and vertebral arteries by measuring the distance from the dye column to uncovertebral joints. The dye radiographic technique provides the surgeon an additional margin of safety.

Follow-Up Defibrillator Testing for Antiarrhythmic Drugs

Probabilism: The doctrine that probability is a sufficient basis for belief or action . Uncertainty: The condition of being in doubt . It has been rigorously demonstrated that implantable cardioverter-defibrillators (ICDs) prolong life as primary and secondary prevention therapies for the management of malignant ventricular tachyarrhythmias. Despite 20 years of clinical use, however, there exist many unresolved issues in ICD therapy.1 Even the most fundamental aspect of ICD implantation, defibrillation threshold (DFT) testing, is not standardized. Determining a DFT is fundamentally different from determining a pacing threshold.1,2 The latter is essentially a fixed value at a given combination of pulse width and voltage. Clinically, there is a sharp demarcation of pacing voltages that capture and those that do not. In contrast, defibrillation is characterized as a probabilistic event based on our current understanding. The dose-response curve for defibrillation is described as sigmoidal in shape with a higher likelihood of success at higher energies.1,2 The possibility of an “outlier” event, defibrillation at low energy, or failure at higher energy remains present. Defining a true defibrillation threshold, ie, that energy above which defibrillation will always succeed and below which it will always fail, is not the goal of defibrillation testing in the clinical setting. Instead, the clinical approach to ICD implantation defines an energy level delivered from a device that has a reasonable likelihood of success. The physician then programs this energy plus an additional safety margin that he or she trusts will compensate for the probabilistic nature of defibrillation. There are many methods to test defibrillation in clinical practice. Methods in clinical use include step down to failure, 2 or 3 successes without failure at a given energy level (DFT+, DFT++), binary search, Bayesian search, 3-reversal method, verification method (single low-energy success), and testing upper limit of vulnerability …

A Study on the Evaluation of Pipe Fracture Characteristics

In order to analyze elastic-plastic fracture behavior of a structure, the materials fracture resistance curve should first be determined. The standard CT specimen was used to obtain fracture resistance curves of a piping system. However, this is known to be very conservative in evaluating the integrity of a structure. In addition, the specimen geometry and dimension due to the constraint effect alters the fracture resistance curve. The objective of this paper is to verify the conservativeness of the fracture resistance curve by the standard CT specimen, subsequently to provide an additional safety margin. To this end, the fracture tests using a real pipe specimen and the standard CT specimen tests were performed. The 4-point bending test method was applied in the pipe test while the direct current potential drop method was used to measure the pipe's crack extension and length. Finite element analyses for J-Q analyses were performed with CT specimens and pipes in order to prove the additional safety margin. From these test results and analyses of both pipe and the standard CT specimen, it was observed that the fracture analysis with the standard CT specimen is conservative and the additional safety margin was proved.

Implications of Monte Carlo Statistical Errors in Criticality Safety Assessments

Most criticality safety calculations are performed using Monte Carlo techniques because of Monte Carlo’s ability to handle complex three-dimensional geometries. For Monte Carlo calculations, the more histories sampled, the lower the standard deviation of the resulting estimates. Therefore, the common intuition is that the more histories the better; as a result, analysts tend to run Monte Carlo analyses as long as possible (or at least to a minimum acceptable uncertainty). For Monte Carlo criticality safety analyses, however, the optimization situation is complicated by the fact that procedures usually require that an extra margin of safety be added because of the statistical uncertainty of the Monte Carlo calculations. This additional safety margin affects the impact of the choice of the calculational standard deviation, both on production and on safety. This paper shows that, under the assumptions of normally distributed benchmarking calculational errors and exact compliance with the upper subcritical limit (USL), the standard deviation that optimizes production is zero, but there is a nonzero value of the calculational standard deviation that minimizes the risk of inadvertently labeling a supercritical configuration as subcritical. Furthermore, this value is shown to be a simple function of the typical benchmarking step outcomes—the bias, the standard deviation of the bias, the USL, and the number of standard deviations added to calculated k-effectives before comparison to the USL.

Robot-assisted evaluation of coordination between grasp and load forces in a power grasp in humans

A novel approach for evaluation of a grasp in humans is presented. The key novelty is combination of a haptic interface with force/torque transducers for measuring the grasp force. This paper presents results of grasp and load force coordination for quasi-static and dynamic external load force disturbances for a power grasp. An elevation of the grasp force is observed in a dynamic task. Elevation of the grasp force is needed for an additional safety margin to ensure a stable grasp.

실배관 파괴특성 평가에 관한 연구

In order to analyze the elastic-plastic fracture behavior of a structure, the fracture resistance curve of the material should be known first. The standard CT specimen was used to obtain the fracture resistance curves of a piping system. However, it is known that the fracture resistance curve by the standard CT specimen is very conservative to evaluate the integrity of a structure. Also the fracture resistance curve is effected by the specimen geometry and the dimensions because of the constraint effect. The objective of this paper is to be certain the conservativeness of the fracture resistance curve by the standard CT specimen and to provide an additional safety margin. For these, the fracture tests using a real pipe specimen and to provide an additional safety margin. For these, the fracture tests using a real pipe specimen and the standard CT specimen test were performed. A 4-point bending jig was manufactured for the pipe test and the direct current potential drop method was used to measure the crack extension and the length for the pipe test. Also finite element analyses were performed with a CT specimen and a pipe in order to prove the additional safety margin. From the result of tests and analyses of the pipe and the standard CT specimen, it was observed that the fractrue analysis with the standard CT specimen is conservative and the additional safety margin was proved.

Managing chronic pain with encapsulated cell implants releasing catecholamines and endogenous opiods

Spinal injections (intrathecal) of norepinephrine and/or opiod agonists are antinociceptive and when administered together may act in synergy. Spinal implants of adrenal chromaffin cells are an effective method for sustained delivery of the analgesic substances norepinephrine and enkephalin to the central nervous system (CNS). One method of packaging and implanting cell-loaded devices into the intrathecal space of recipients is by encapsulating the cell suspensions in a polymer membrane prior to implantation. Cells/tissue packaged within an encapsulating membrane obviate the need for immunosuppressive therapies in transplant recipients. In addition, device output can be quantified prior to implantation, and following the removal of the spinal implant. The ability to retrieve the devices with the present tubular configuration also confers an additional margin of safety over unencapsulated chromaffin cell implants. This paper reviews the research and clinical observations of cellular transplants containing adrenal chromaffin cells for relieving chronic pain. Encapsulated cell technology is discussed with an emphasis on our experiences developing pain-modulating clinical devices. The human-sized prototype devices were loaded with enzymatically isolated bovine chromaffin cells and maintained in vitro for 7 - 8 days in serum-free media. Two days prior to implantation, each device was assayed by static incubation to measure catecholamine and met-enkephalin output, and qualified devices (n = 6) were implanted into the sheep subarachnoid space for 6 weeks. Following a 6 week in life period, the retrieval forces of prototype devices were measured during removal from the subarachnoid space. Static incubation of the devices immediately following retrieval and after a 24 hour re-incubation period were used to quantify norepinephrine and met-enkephalin secretion profiles. This study demonstrated the safety, retrievability and maintenance of pharmacologically active encapsulated chromaffin cell-loaded devices with human implant dimensions.

Percutaneous radiofrequency ablation of liver tumors using the LeVeen 4 cm array probe

The purpose of this study was to evaluate safety and efficacy of a radiofrequency ablation system in clinical practice. In 35 patients (age 63,9 +/- 12,6 years, range 22 - 83) a total of 65 liver tumors were percutaneously treated using a 200 watt radiofrequency generator and a LeVeen 4 cm array probe (RF3000, Boston Scientific). The interventions were performed under CT guidance in local anaesthesia and sedation. Adapted to the tumor size, the LeVeen Probe was repositioned during the procedure with an additional safety margin of 1 cm. Primary tumors were colorectal in 22, and mamma tumors (n = 4), zystic pancreas tumors (n = 2), gastric cancer (n = 1), zystadenocarcinoma of the liver (n = 1), lung cancer (n = 1), gastrointestinal stroma tumor (n = 1), duodenal carcinoma (n = 1), cholangiocellular carcinoma (n = 1) and hepatocellular carcinoma (n = 1). Post interventional control and follow-up was performed with multislice-CT (collimation 2.5 mm, unenhanced and contrast enhanced, arterial and portal filling) at 4 weeks, and every three months. One to 4 metastases were treated per patient during one or up to 4 procedure sessions. Mean lesion size was 2,3 +/- 1,2 cm (range 0,2 to 7,0). The corresponding size of the necrosis achieved was 4,6 +/- 1,4 cm (range 2,0 - 8,2). Primary technical success with complete tumor ablation was reached in 60 of 65 lesions. In 4 cases two treatment sessions were necessary in order to achieve the intended results. In one case the procedure was aborted because of a close relationship between lesion and right colon. 63 tumors were treated in sedation and local anesthesia. General anesthesia was necessary in two cases, in one who refused intervention in sedation, and in another case with insufficient analgetic effect. Morbidity was 9.2 %: Bleeding complications (n = 3, one arterial bleeding from the ablation tract, two intrahepatic bleedings with extrahepatic hematoma) were confirmed by selective angiography of the hepatic artery and were treated with coil embolisation of the respective segmental arteries. One case with subcapsular tumor ablation suffered from a large subcapsular hematoma requiring a blood transfusion. In one case with a subphrenic location of the metastasis, the needle electrode had passed the costophrenic recessus and resulted in an hematothorax. This patient was treated by pleural drainage for two days. One patient suffered from fever up to 39 degrees C and inflammation of the biliary tract and received a cholecystectomy 22 days post interventionally. There was no peri interventional mortality. Mean follow-up is 5,6 +/- 3,3 months (range 0 to 13). 21 of 35 patients showed no evidence of tumor recurrence. One case is scheduled for a second treatment session for complete tumor ablation. 13 of 35 patients suffered from tumor recurrence, either local recurrences and/or new metastases. At the sites of prior RF-ablation 9 local recurrences were detected in 7 patients, two cases with isolated local recurrences and 5 cases with local recurrences and new metastases. 6 Patients showed no evidence for local recurrences but new metastases. In these 11 cases a total of 37 metastases were found at new locations. In three patients tumor recurrence was treated by means of a second RF-ablation. The remaining 10 patients received chemotherapy. RF-ablation can be performed in local anaesthesia and sedation with low peri interventional morbidity and mortality. Using the LeVeen probe and a 200 watt generator, appropriate necroses can be achieved. CT follow-up is required every three months because of the tumor recurrence rate and reinterventions may be required.

Organ motion, set-up variation and treatment margins in radical radiotherapy of urinary bladder cancer

Background and purpose: A major challenge in conformal radiotherapy of bladder cancer is to determine adequate treatment margins. For this purpose, we therefore quantified the internal motion of the urinary bladder as well as the external patient set-up variation during a course of fractionated radiotherapy. In the light of the recently introduced ICRU-62 concept, the planning organ at risk volume, we also studied the internal motion of nearby organs at risk, the rectum and intestine. Material and methods: Weekly CT scans and electronic portal images (EPIs) were sampled from 20 patients during radical, conformal bladder irradiation (60–64 Gy/2 Gy in five fractions weekly). The planning scans were acquired with 70 ml of bladder contrast instilled, and patients were instructed to void before the treatment/repeat scanning sessions. Internal motion of the bladder, rectum and intestine was measured by 3-D image matching of the repeat scans to the patients’ planning scans. Internal margins (CTV-to-ITV) were determined using both a direct empirical approach and an analytically derived margin recipe. The external patient set-up variability was determined by 2-D matching of front and lateral EPIs to corresponding digitally reconstructed radiographs. Results: A total of 149 CT scans (20 for planning, 129 during the treatment course) and 133 sets of EPIs were analysed. Bladder volumes were smaller during treatment than in the planning situation in 85% of the repeat scans. Nevertheless, we found the repeat scan bladder volumes to extend outside the planning scan bladder contours in 89% of the scans, on average with 9% of the volume (range: 0–47%). Eight patients (40%) had at least one repeat scan (25 scans in total) where displacements >15 mm were observed at one or more sides of the bladder. CTV-to-ITV margins of 10 mm inferior, 20 mm superior, 11 mm left, 8 mm right, 20 mm anterior and 14 mm posterior were required to simultaneously encompass all bladder deflections except for the largest outward deflection in all directions in 84% of the patients. Including patient set-up variation (CTV-to-PTV), we found that an additional safety margin of 2–6 mm had to be added in the various directions. The rectum expanded outside the planning contours in all repeat scans, on average with 24% of the volume (range: 2–69%). The volume of intestine found close to the bladder were significantly and negatively correlated to the bladder volume in almost half of the patients. Conclusion: This study documented both a large internal motion of the bladder and a substantial patient set-up variation. Our current treatment margins have been adjusted according to the findings of this study. Considerable variation in position and volume of the rectum and intestine was also documented.

Low pH, caprylate incubation as a second viral inactivation step in the manufacture of albumin: Parametric and validation studies

Caprylate has long been used as a stabiliser for albumin solutions, as well as a precipitation agent for immunoglobulins, ceruloplasmin and more recently in removing contaminants during albumin purification. Its virucidal properties have been explored and it has been proposed that the non-ionised form of the caprylate acid disrupts the integrity of the lipid bilayer and membrane associated proteins of enveloped viruses. The studies reported here further explore the use of this fatty acid to inactivate lipid-enveloped viruses in albumin manufactured for therapeutic use. Caprylate concentrations considered above solubility limits were adopted. Acidic pH was used to maximise the percentage of non-ionised caprylate and elevated temperatures were used to enhance inactivation rates. Parameters were manipulated to determine the relationship between pH, temperature and caprylate: protein ratio. These studies demonstrated that elevated temperature and low pH were critical in achieving significant reduction in virus infectivity and that the rate and extent of inactivation was sensitive to changes in caprylate:protein ratio and to changes in pH. Final inactivation conditions of 10% w/v protein, 16 mM caprylate, pH 4.5 and 30 °C were chosen to minimise protein dimerisation and to achieve greater than 4 log 10inactivation of the most resistant virus tested, bovine viral diarrhoea virus. Validation studies using both model and relevant blood borne viruses demonstrated this to be a robust and effective viral inactivation step and is complementary to the commonly used pasteurisation viral inactivation step, thus providing an additional margin of safety to this valuable therapeutic blood product.

Glutaraldehyde in hospital wastewater.

Glutaraldehyde (GA) solutions are widely used in hospitals to disinfect reusable fiber-optic endoscopes. These solutions are dumped after use in the aquatic environment without any particular safety precautions. Taking into account the quantity of GA consumed daily and the released water volume, the predicted hospital wastewater concentration was estimated at 0.50 mg/L. To measure the real GA concentration present in hospital wastewater, we developed an analytical technique that is simple, sensitive, and reliable. This method consists of a water sample concentration and purification by solid phase extraction and then a spectrophotometric determination. This analytical method was used for a 1-week surveillance program at Rouen University Hospital (2,600 beds). The wastewater tested showed the presence of a concentrated peak approximately eight times higher than the predicted wastewater concentration. The environmental impact of GA release into the aquatic environment was then studied. A predicted no-effect concentration (PNEC) < 1 microg/L was calculated. In most situations the predicted environmental concentration (PEC) was found to be <0.5 microg/L taking into account the hospital wastewater dilution in its way to the sewage treatment plant and GA biodegradation. The PEC/PNEC ratio is then < 1, showing that this release are not expected to present a significant risk to the aquatic environment. However in situations of insufficient dilution or of major release, the PEC/PNEC ratio become > 1, and an environmental risk should be expected. An internal prevention program of the various hospital departments to assure GA rational use, and a release spreading would give an additional safety margin to consider GA as safe in terms of environmental risk.

Inhibition of Listeria monocytogenes by Sodium Diacetate and Sodium Lactate on Wieners and Cooked Bratwurst

The inhibition of Listeria monocytogenes by sodium lactate and sodium diacetate was evaluated for wieners containing pork, turkey, and beef and for cooked bratwurst containing beef and pork. Both products were supplied by commercial manufacturers. Treated products were surface-inoculated with 105 CFU of L. monocytogenes per package and vacuum-packed in gas-impermeable pouches. Wieners were stored for 60 days at 4.5°C, and bratwurst were stored for 84 days at 3 and 7°C. A surface treatment that consisted of dipping wieners into solutions containing ≤6% lactate and ≤3% diacetate for 5 s did not delay pathogen growth compared with that for untreated wieners. In additional trials, the antilisterial activity of lactate and diacetate in wiener and bratwurst formulations was evaluated. Lactate levels ranged from 1.32 to 3.4%, and diacetate was evaluated at 0.1 and 0.25%. The growth of L. monocytogenes was delayed for 4 and 12 weeks at 7 and 3°C, respectively, on uncured, unsmoked bratwurst formulated with 3.4% lactate/0.1% diacetate, compared with 1 and 2 weeks, respectively, for the formulation containing 2% lactate. L. monocytogenes grew by ≥1 log unit after 4 weeks' storage at 3 or 7°C on cured, smoked bratwurst without lactate or diacetate, but growth was inhibited for 12 weeks on cured, smoked bratwurst formulated with 3.4% lactate and 0.1% diacetate. Sodium lactate levels of ≥3% and combinations of ≥1% lactate plus ≥0.1% diacetate prevented listerial growth on wieners stored for 60 days at 4.5°C. These results indicate that dipping wieners in lactate-diacetate solutions is not an efficient way to apply these antimicrobial agents to wieners. However, the inclusion of combinations of sodium lactate and sodium diacetate in wiener or bratwurst formulations inhibits the growth of L. monocytogenes at ≤7°C, and an additional margin of safety was observed for products that are cured and smoked.