Administrative improvements

Both the safety studies for shutdown and low power operation and the operational experience of plants world-wide have confirmed that the human interactions of various kinds are significant contributors to the overall risk level. This is naturally the consequence of more human interactions during shutdown (both maintenance and operations, as most of the automatic signals are blocked or disconnected) but also the fact that most of the plants internationally have relatively few administrative limitations and requirements as compared to the power operations. 

The shutdown state was traditionally considered the safe state of the reactors so the technical specification requirements were seen as not necessary. That lead to the fact that very little administrative control was in place to assure the availability of systems and equipment. Moreover, the outage scheduling was in most of the cases centered on maintenance activities with less regard to available redundancies etc. 

Newer plants, in general, tend to have more developed technical specifications for shutdown operations. Some plants have modified their technical specifications to address the shutdown operations. Those technical specifications would then tend to follow the same format as for the power operation. 

The technical specification is a preferred way of dealing with the shutdown safety issues in the USA. The USA regulators determined that the technical specification requirements would be appropriate for assuring the safety in shutdown. Most of the European countries required utilities to perform a PSA study and identify possible improvements for shutdown operations. 

Increasing popularity of Technical specifications for shutdown clearly indicate that the shutdown safety is to a large extent the configuration control issue. Technical specifications in most cases introduce somewhat rigid requirements, which is somewhat detrimental for shutdown operations, where the necessary availability of equipment and allowed configurations depends highly on the decay heat level etc. 

The safety studies for low power operation and for shutdown have confirmed that human interactions are among the most important contributors to the overall risk. This is caused by 

The recent safety studies also indicate that shutdown safety is to a large extent a configuration control issue. 

Among the countries and plants that discussed their activities on the topic at the recent meeting, there are different approaches to administrative limitations during shutdown. These depend both on the reactor type and on the overall safety culture in a given country. 

Most of the plants have considered some review relevant to shutdown operations and/or additions to their limits and conditions. However, this process depends on the present status and completeness of their LPS studies. 

The administrative limitations addressing shutdown operations should be focused on assuring the availability of additional redundancies or limitation of the duration of specific critical operating modes. Some specific improvements to the limits and conditions that should be considered are  

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Electrotransport technology offers a number of benefits for therapeutic appHcations, including systemic or local adininistration of a wide variety of therapeutic agents with the potential adininistration of peptides and proteins long-term noninvasive administration, improving convenience and compliance controlled release, providing a desired deflvery profile over an extended period with rapid onset of efficacious plasma dmg levels and in some cases reduced side effects and a transport rate relatively independent of skin type or site. Additional benefits include easy inception and discontinuation of treatment, patterned and feedback-controlled deflvery, and avoidance of first-pass hepatic metaboHsm. 

Inhaled tobramycin (TOBI ) is typically administered to patients 6 years of age and older in alternating 28-day cycles of 300 mg nebulized twice daily, followed by a 28-day washout or off period to minimize development of resistance. Longterm intermittent administration improves pulmonary function, decreases microbial burden, and reduces the need for hospitalization for IV therapy.24,25 Due to minimal systemic absorption, pharmacokinetic monitoring is not necessary with normal renal function. Lower doses of nebulized tobramycin solution for injection have been used in younger children, and studies are underway using 300 mg twice daily in children under age 6. 

Administration, Improved Flammability Standards for Materials Used in the Interiors of Transport Category Airplane Cabins Final Rule. 14 CFR Parts 25 and 121. Federal Register, 53 (165) pp. 32564-81, Aug. 25,... 

There is evidence that nicotine administration improves performance on tasks that require vigilant attention in nicotine-dependent smokers (Newhouse et al. 2004). Nicotine administration also has been reported to improve reaction time, regardless of smoking status (Ernst et al. 2001a). Consistent with these findings are studies that demonstrate that acute abstinence from smoking (within 12 h) results in slowed response times (Bell et al. 1999 Gross et al. 1993 Thompson et al. 2002). 

The mechanism of deprenyl s action is unclear. In addition to enhancing dopaminergic activity in the brain by inhibiting dopamine degradation, deprenyl is metabolized into various stimulant metabolites. In spontaneously hyperactive rats used in an animal model of ADHD, chronic deprenyl administration improved im-pulsivity (but not hyperactivity or attention) along with altering levels of noradrenaline, dopamine, and serotonin and their metabolites (Boix et ah, 1998). 

L.A. Valenskaya et al showed that in children suffering from dysentery, Enterosgel administration improves digestion of maltose, studied by the method of... 

Zhang H, Osada K, Sone H, and Furukawa Y (1997) Biotin administration improves the impaired glucose tolerance of streptozotocin-induced diabetic Wistar tats. Journal of Nutritional Science and Vitaminology (Tokyo) 43,271-80. 

The risks and benefits of distal tubular diuretics have been assessed in preterm infants under 3 weeks of age with or developing chronic lung disease (36). Acute and chronic administration of distal diuretics improved pulmonary mechanics adverse effects were not reported. However, additional studies are needed to assess whether thiazide administration improves mortality, duration of oxygen dependency, ventilator dependency, length of hospital stay, and long-term outcome in patients exposed to corticosteroids and bronchodilators, and whether adding spironolactone to thiazides or adding metolazone to furosemide has any beneficial effect. 

Since the two meta-analyses in 1995, five prospective, randomized, controlled trials of low-dose corticosteroids in vasopressor-dependent septic shock patients (n = 505) have been published. " These smdies used moderate physiologic doses (200 to 300 mg/day) of hydrocortisone. A meta-analysis of these studies showed that steroid therapy was associated with an overall improvement in survival rate (odds ratio [OR] 1.52, 95% confidence interval [Cl] 1.03-2.27 p =. 036) and shock reversal (OR 4.79, 95% Cl 2.07-11.11 p =. 001). These effects were beneficial in both responders and nonresponders to corticotrophin stimulation testing (p =. 63 and p =. 75, respectively). These smdies also showed that low-dose corticosteroid administration improves hemodynamics and reduces the duration of vasopressor support. " All these studies differ from earlier smdies in that steroids were admimstered later in septic shock (23 hours versus less than 2 hours p =. 02). In these studies, steroids were administered longer (6 days versus 1 day p =. 004), doses were tapered, lower doses were used (hydrocortisone eqmvalents 1209 mg versus 23,975 mg p =. 01), aU patients received high doses of catecholamine vasopressors, and control groups had higher mortality rates (mean 57% versus 34% p =. 03). Since only one of the five studies showed a mortality benefit of low-dose steroids in septic shock, further research is required to confirm this finding. ... 

I Liquid preparations (e.g. risperidone, fluoxetine) and oral dispersible tablets (e.g. olanzapine, risperidone, mirtazapine) are aimed at ensuring administration/improving compliance. They generally have minimal effects on absorption. 

Drug-induced tubulointerstitial nephritis represents 1-10% of cases of acute renal failure and is characterized by infiltrates of mononuclear cells with tubular cell injury [49]. Most of the patients exhibit enhanced serum IgE levels, hypereosinophilia and/or hy-pereosinophiluria, fever and skin rashes. Most often, withdrawal of the drug, with or without concomitant steroid administration, improves the renal functions. 

Hardware modifications resulting from accident analysis, SPSA and operating experience should be implemented as soon as possible together with administrative improvements. 

For application of 40-50 ml contrast agent at a flux of 5-10 ml/s, a central venous catheter or an 18-gauge injection catheter at the cubital vein is mandatory. Using a saline pusher at the same injection speed directly after contrast agent administration improves the quality of the arterial input function. 

Lee J, Lee HK, Kim CY, Hong YJ, Choe CM, You TW, Seong GJ (2005) Purified high-dose anthocyanoside oligomer administration improves nocturnal vision and clinical symptoms in myopia subjects. Br J Nutr 93 895... 

Assuming that these administrative improvements are made, the risk assessment group decided that the Probability of occurrence of an illness from a chemical exposure would be Seldom (2) and that the Severity of harm expected would be Negligible (2). Thus, the Risk Score is 4—in the Low Risk Category. 

CASE STUDY US FEDERAL AVIATION ADMINISTRATION, IMPROVING OVERSIGHT THROUGH SYSTEM SAFETY... 

Specific administrative improvements dealing with each of the areas of safety interest are presented next. 

Administrative improvements related to the mitigation systems include mainly a more systematic approach to outage planning where umbrella schedules are being developed covering a series of systems, to prevent opposing unavailability of trains of front line systems and support systems. 

Other interesting operational improvements for shutdown operation include a general review of applicability of procedures, development of an umbrella system of activities and development of specific post maintenance testing schemes. Development of an operating plan for shutdown which would indicate the required operability of systems and equipment could also be considered among operational improvements (some plants may call this an administrative improvement). 

The review of actual safety enhancement focused on shutdown and low power operations presented in this report clearly indicate that there are different possible solutions for similar safety concerns. The improvements selected by specific countries and plants point out to different preferences or conveniences. While some countries concentrate on administrative improvements, other appear to favour interlocks and information systems. Some prefer training and operator information tools, other develop and put in practice the emergency operating procedures. 

SAFETY AREA 1 ADMINISTRATIVE IMPROVEMENTS 1 HARDWARE IMPROVEMENTS 1 OPERATIONAL IMPROVEMENTS... 

The PFPB expanded access to medication for the most common diseases, benefitting people on low incomes and enabling access to low-cost medicines for users of the private health network. Federal government initiatives included centralization of the medicines procurement and administrative improvements. Medicines were acquired, distributed and managed centrally by FIOCRUZ, a unit of the Ministry of Health. This procurement strategy was underpinned by a guarantee of state funding. 

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