STATUS OF BROMETHALIN OUTSIDE THE UNITED STATES

ABSTRACT: Bromethalin has been extensively researched over the past decade in the United States, Switzerland, England, Denmark, and France. United States EPA registrations were received in 1982 and commercial pelleted formulations containing 0.01% bromethalin were developed and introduced in the USA by Ralston Purina (ASSAULT1*) in 1985 and Velsicol (VENGEANCE1*) in 1986. Ciba-Geigy is currently developing new formulations under the tradename DORATIDR for use outside the United States. Bromethalin acute toxicity and 14-day subchronic studies are reviewed and data from recently completed 90-day subchronic studies required for registration outside the US are presented. Pharmacodynamic studies have shown that bromethalin acts as an uncoupler of oxidative phosphorylation, thus interrupting the vital production of ATP necessary to maintain essential metabolic functions. Laboratory and field trial data are presented from Switzerland, France, England, and Denmark that indicate the effectiveness of new bromethalin formulations against anticoagulant resistant and susceptible rodents. A comparative rodenticide pen testing system is described from which test results confirm bromethalin's quick action and feed consumption efficiency when compared to second-generation anticoagulants.

A Fixed Netting System as a Means of Excluding Birds From a Domestic Waste Landfill

Many bird species are attracted to landfills which take domestic or putrescible waste. These sites provide a reliable, rich source of food which can attract large concentrations of birds. The birds may cause conflicts with human interest with respect to noise, birds carrying litter off site, possible transmission of pathogens in bird droppings and the potential for birdstrikes. In the UK there is an 8 mile safeguarding radius around an airfield, within which any planning applications must pass scrutiny from regulatory bodies to show they will not attract birds into the area and increase the birdstrike risk. Peckfield Landfill site near Leeds, West Yorkshire was chosen for a trial of a netting system designed to exclude birds from domestic waste landfills. The site was assessed for bird numbers before the trial, during the netting trial and after the net had been removed. A ScanCord net was installed for 6 weeks, during which time all household waste was tipped inside the net. Gull numbers decreased on the site from a mean of 1074 per hourly count to 29 per hourly count after two days. The gull numbers increased again after the net had been removed. Bird concentrations in the surroundings were also monitored to assess the effect of the net. Bird numbers in the immediate vicinity of the landfill site were higher than those further away. When the net was installed, the bird concentrations adjacent to the landfill site decreased. Corvids were not affected by the net as they fed on covered waste which was available outside the net throughout the trial. This shows that bird problems on a landfill site are complex, requiring a comprehensive policy of bird control. A supporting bird scaring system and clear operating policy for sites near to airports would be required.

Glucose Control in Acute Myocardial Infarction: A Pilot Randomized Study Controlled by Continuous Glucose Monitoring System Comparing the Use of Insulin Glargine with Standard of Care

Background: This pilot study aimed to verify if glycemic control can be achieved in type 2 diabetes patients after acute myocardial infarction (AMI), using insulin glargine (iGlar) associated with regular insulin (iReg), compared with the standard intensive care unit protocol, which uses continuous insulin intravenous delivery followed by NPH insulin and iReg (St. Care). Patients and Methods: Patients (n = 20) within 24 h of AMI were randomized to iGlar or St. Care. Therapy was guided exclusively by capillary blood glucose (CBG), but glucometric parameters were also analyzed by blinded continuous glucose monitoring system (CGMS). Results: Mean glycemia was 141 +/- 39 mg/dL for St. Care and 132 +/- 42 mg/dL for iGlar by CBG or 138 +/- 35 mg/dL for St. Care and 129 +/- 34 mg/dL for iGlar by CGMS. Percentage of time in range (80-180 mg/dL) by CGMS was 73 +/- 18% for iGlar and 77 +/- 11% for St. Care. No severe hypoglycemia (<= 40 mg/dL) was detected by CBG, but CGMS indicated 11 (St. Care) and seven (iGlar) excursions in four subjects from each group, mostly in sulfonylurea users (six of eight patients). Conclusions: This pilot study suggests that equivalent glycemic control without increase in severe hyperglycemia may be achieved using iGlar with background iReg. Data outputs were controlled by both CBG and CGMS measurements in a real-life setting to ensure reliability. Based on CGMS measurements, there were significant numbers of glycemic excursions outside of the target range. However, this was not detected by CBG. In addition, the data indicate that previous use of sulfonylurea may be a potential major risk factor for severe hypoglycemia irrespective of the type of insulin treatment.

Sedation and weaning from mechanical ventilation: effects of process optimization outside a clinical trial

PURPOSE: We studied the effects of reorganization and changes in the care process, including use of protocols for sedation and weaning from mechanical ventilation, on the use of sedative and analgesic drugs and on length of respiratory support and stay in the intensive care unit (ICU). MATERIALS AND METHODS: Three cohorts of 100 mechanically ventilated ICU patients, admitted in 1999 (baseline), 2000 (implementation I, after a change in ICU organization and in diagnostic and therapeutic approaches), and 2001 (implementation II, after introduction of protocols for weaning from mechanical ventilation and sedation), were studied retrospectively. RESULTS: Simplified Acute Physiology Score II (SAPS II), diagnostic groups, and number of organ failures were similar in all groups. Data are reported as median (interquartile range).Time on mechanical ventilation decreased from 18 (7-41) (baseline) to 12 (7-27) hours (implementation II) (P = .046), an effect which was entirely attributable to noninvasive ventilation, and length of ICU stay decreased in survivors from 37 (21-71) to 25 (19-63) hours (P = .049). The amount of morphine (P = .001) and midazolam (P = .050) decreased, whereas the amount of propofol (P = .052) and fentanyl increased (P = .001). Total Therapeutic Intervention Scoring System-28 (TISS-28) per patient decreased from 137 (99-272) to 113 (87-256) points (P = .009). Intensive care unit mortality was 19% (baseline), 8% (implementation I), and 7% (implementation II) (P = .020). CONCLUSIONS: Changes in organizational and care processes were associated with an altered pattern of sedative and analgesic drug prescription, a decrease in length of (noninvasive) respiratory support and length of stay in survivors, and decreases in resource use as measured by TISS-28 and mortality.

Avant-garde or supplement? Advisory bodies of transnational associations as alternatives to the League’s Minority Protection System, 1919-1939

This exegesis focuses on the work of minority committees of transnational associations in the interwar period. Most of their members considered the League system to be inefficient and supported the establishment of non-state alternatives, which included private investigations on the spot, publicity for specific problems of minorities, and attempts to reconcile representatives of ethnic minorities with those of the majority. Members of non-involved states were pre-destined especially to act as neutral moderators. Only those in close contact with League officials avoided being misused by political forces that did not seek reconciliation but border revision. They learnt that the League rules looked inadequate from the outside but turned out to be useful in coming to applicable solutions once they started their own alternative methods. Their publications and investigative journeys turned out to deepen the problems, whilst their reconciliation work became an appreciated supplement of the League system.

A novel clinical scoring system for outcome prediction in dogs with acute kidney injury managed by hemodialysis.

BACKGROUND No reliable tool to predict outcome of acute kidney injury (AKI) exists. HYPOTHESIS A statistically derived scoring system can accurately predict outcome in dogs with AKI managed with hemodialysis. ANIMALS One hundred and eighty-two client-owned dogs with AKI. METHODS Logistic regression analyses were performed initially on clinical variables available on the 1st day of hospitalization for relevance to outcome. Variables with P< or = .1 were considered for further analyses. Continuous variables outside the reference range were divided into quartiles to yield quartile-specific odds ratios (ORs) for survival. Models were developed by incorporating weighting factors assigned to each quartile based on the OR, using either the integer value of the OR (Model A) or the exact OR (Models B or C, when the etiology was known). A predictive score for each model was calculated for each dog by summing all weighting factors. In Model D, actual values for continuous variables were used in a logistic regression model. Receiver-operating curve analyses were performed to assess sensitivities, specificities, and optimal cutoff points for all models. RESULTS Higher scores were associated with decreased probability of survival (P < .001). Models A, B, C, and D correctly classified outcomes in 81, 83, 87, and 76% of cases, respectively, and optimal sensitivities/specificities were 77/85, 81/85, 83/90 and 92/61%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE The models allowed outcome prediction that corresponded with actual outcome in our cohort. However, each model should be validated further in independent cohorts. The models may also be useful to assess AKI severity.

The ciao prolog system

Ciao is a public domain, next generation multi-paradigm programming environment with a unique set of features: Ciao offers a complete Prolog system, supporting ISO-Prolog, but its novel modular design allows both restricting and extending the language. As a result, it allows working with fully declarative subsets of Prolog and also to extend these subsets (or ISO-Prolog) both syntactically and semantically. Most importantly, these restrictions and extensions can be activated separately on each program module so that several extensions can coexist in the same application for different modules. Ciao also supports (through such extensions) programming with functions, higher-order (with predicate abstractions), constraints, and objects, as well as feature terms (records), persistence, several control rules (breadth-first search, iterative deepening, ...), concurrency (threads/engines), a good base for distributed execution (agents), and parallel execution. Libraries also support WWW programming, sockets, external interfaces (C, Java, TclTk, relational databases, etc.), etc. Ciao offers support for programming in the large with a robust module/object system, module-based separate/incremental compilation (automatically -no need for makefiles), an assertion language for declaring (optional) program properties (including types and modes, but also determinacy, non-failure, cost, etc.), automatic static inference and static/dynamic checking of such assertions, etc. Ciao also offers support for programming in the small producing small executables (including only those builtins used by the program) and support for writing scripts in Prolog. The Ciao programming environment includes a classical top-level and a rich emacs interface with an embeddable source-level debugger and a number of execution visualization tools. The Ciao compiler (which can be run outside the top level shell) generates several forms of architecture-independent and stand-alone executables, which run with speed, efficiency and executable size which are very competive with other commercial and academic Prolog/CLP systems. Library modules can be compiled into compact bytecode or C source files, and linked statically, dynamically, or autoloaded. The novel modular design of Ciao enables, in addition to modular program development, effective global program analysis and static debugging and optimization via source to source program transformation. These tasks are performed by the Ciao preprocessor ( ciaopp, distributed separately). The Ciao programming environment also includes lpdoc, an automatic documentation generator for LP/CLP programs. It processes Prolog files adorned with (Ciao) assertions and machine-readable comments and generates manuals in many formats including postscript, pdf, texinfo, info, HTML, man, etc. , as well as on-line help, ascii README files, entries for indices of manuals (info, WWW, ...), and maintains WWW distribution sites.

Unattended motion detection system based on the mammalian retina

Sensing systems in living bodies offer a large variety of possible different configurations and philosophies able to be emulated in artificial sensing systems. Motion detection is one of the areas where different animals adopt different solutions and, in most of the cases, these solutions reflect a very sophisticated form. One of them, the mammalian visual system, presents several advantages with respect to the artificial ones. The main objective of this paper is to present a system, based on this biological structure, able to detect motion, its sense and its characteristics. The configuration adopted responds to the internal structure of the mammalian retina, where just five types of cells arranged in five layers are able to differentiate a large number of characteristics of the image impinging onto it. Its main advantage is that the detection of these properties is based purely on its hardware. A simple unit, based in a previous optical logic cell employed in optical computing, is the basis for emulating the different behaviors of the biological neurons. No software is present and, in this way, no possible interference from outside affects to the final behavior. This type of structure is able to work, once the internal configuration is implemented, without any further attention. Different possibilities are present in the architecture to be presented: detection of motion, of its direction and intensity. Moreover, some other characteristics, as symmetry may be obtained.

A "Free-Lunch" tour of the Jovian System

An ED-tether mission to Jupiter is presented. A bare tether carrying cathodic devices at both ends but no power supply, and using no propellant, could move 'freely' among Jupiter's 4 great moons. The tour scheme would have current naturally driven throughout by the motional electric field, the Lorentz force switching direction with current around a 'drag' radius of 160,00 kms, where the speed of the jovian ionosphere equals the speed of a spacecraft in circular orbit. With plasma density and magnetic field decreasing rapidly with distance from Jupiter, drag/thrust would only be operated in the inner plasmasphere, current being near shut off conveniently in orbit by disconnecting cathodes or plugging in a very large resistance; the tether could serve as its own power supply by plugging in an electric load where convenient, with just some reduction in thrust or drag. The periapsis of the spacecraft in a heliocentric transfer orbit from Earth would lie inside the drag sphere; with tether deployed and current on around periapsis, magnetic drag allows Jupiter to capture the spacecraft into an elliptic orbit of high eccentricity. Current would be on at succesive perijove passes and off elsewhere, reducing the eccentricity by lowering the apoapsis progressively to allow visits of the giant moons. In a second phase, current is on around apoapsis outside the drag sphere, rising the periapsis until the full orbit lies outside that sphere. In a third phase, current is on at periapsis, increasing the eccentricity until a last push makes the orbit hyperbolic to escape Jupiter. Dynamical issues such as low gravity-gradient at Jupiter and tether orientation in elliptic orbits of high eccentricity are discussed.

Subcutaneous vaccination with irradiated, cytokine-producing tumor cells stimulates CD8+ cell-mediated immunity against tumors located in the "immunologically privileged" central nervous system.

Vaccination with cytokine-producing tumor cells generates potent immune responses against tumors outside the central nervous system (CNS). The CNS, however, is a barrier to allograft and xenograft rejection, and established tumors within the CNS have failed to respond to other forms of systemic immunotherapy. To determine what barriers the "immunologically privileged" CNS would pose to cytokine-assisted tumor vaccines and what cytokines would be most efficacious against tumors within the CNS, we irradiated B16 murine melanoma cells producing murine interleukin 2 (IL-2), IL-3, IL-4, IL-6, gamma-interferon, or granulocyte-macrophage colony stimulating factor (GM-CSF) and used these cells as subcutaneous vaccines against tumors within the brain. Under conditions where untransfected B16 cells had no effect, cells producing IL-3, IL-6, or GM-CSF increased the survival of mice challenged with viable B16 cells in the brain. Vaccination with B16 cells producing IL-4 or gamma-interferon had no effect, and vaccination with B16 cells producing IL-2 decreased survival time. GM-CSF-producing vaccines were also able to increase survival in mice with pre-established tumors. The response elicited by GM-CSF-producing vaccines was found to be specific to tumor type and to be abrogated by depletion of CD8+ cells. Unlike the immunity generated against subcutaneous tumors by GM-CSF, however, the effector responses generated against tumors in the CNS were not dependent on CD4+ cells. These data suggest that cytokine-producing tumor cells are very potent stimulators of immunity against tumors within the CNS, but effector responses in the CNS may be different from those obtained against subcutaneous tumors.

The vertebrate alcohol dehydrogenase system: variable class II type form elucidates separate stages of enzymogenesis.

A mixed-class alcohol dehydrogenase has been characterized from avian liver. Its functional properties resemble the classical class I type enzyme in livers of humans and animals by exhibiting low Km and kcat values with alcohols (Km = 0.7 mM with ethanol) and low Ki values with 4-methylpyrazole (4 microM). These values are markedly different from corresponding parameters of class II and III enzymes. In contrast, the primary structure of this avian liver alcohol dehydrogenase reveals an overall relationship closer to class II and to some extent class III (69 and 65% residue identities, respectively) than to class I or the other classes of the human alcohol dehydrogenases (52-61%), the presence of an insertion (four positions in a segment close to position 120) as in class II but in no other class of the human enzymes, and the presence of several active site residues considered typical of the class II enzyme. Hence, the avian enzyme has mixed-class properties, being functionally similar to class I, yet structurally similar to class II, with which it also clusters in phylogenetic trees of characterized vertebrate alcohol dehydrogenases. Comparisons reveal that the class II enzyme is approximately 25% more variable than the "variable" class I enzyme, which itself is more variable than the "constant" class III enzyme. The overall extreme, and the unusual chromatographic behavior may explain why the class II enzyme has previously not been found outside mammals. The properties define a consistent pattern with apparently repeated generation of novel enzyme activities after separate gene duplications.

Mineralogical compositions of sediment samples from the San Francisco Bay coastal system

The mineralogical compositions of 119 samples collected from throughout the San Francisco Bay coastal system, including bayfloor and seafloor, area beaches, cliff outcrops, and major drainages, were determined using X-ray diffraction (XRD). Comparison of the mineral concentrations and application of statistical cluster analysis of XRD spectra allowed for the determination of provenances and transport pathways. The use of XRD mineral identifications provides semi-quantitative compositions needed for comparisons of beach and offshore sands with potential cliff and river sources, but the innovative cluster analysis of XRD diffraction spectra provides a unique visualization of how groups of samples within the San Francisco Bay coastal system are related so that sand-sized sediment transport pathways can be inferred. The main vector for sediment transport as defined by the XRD analysis is from San Francisco Bay to the outer coast, where the sand then accumulates on the ebb tidal delta and also moves alongshore. This mineralogical link defines a critical pathway because large volumes of sediment have been removed from the Bay over the last century via channel dredging, aggregate mining, and borrow pit mining, with comparable volumes of erosion from the ebb tidal delta over the same period, in addition to high rates of shoreline retreat along the adjacent, open-coast beaches. Therefore, while previously only a temporal relationship was established, the transport pathway defined by mineralogical and geochemical tracers support the link between anthropogenic activities in the Bay and widespread erosion outside the Bay. The XRD results also establish the regional and local importance of sediment derived from cliff erosion, as well as both proximal and distal fluvial sources. This research is an important contribution to a broader provenance study aimed at identifying the driving forces for widespread geomorphic change in a heavily urbanized coastal-estuarine system.

Determining the specification of a control system from that of its environment

Well understood methods exist for developing programs from given specifications. A formal method identifies proof obligations at each development step: if all such proof obligations are discharged, a precisely defined class of errors can be excluded from the final program. For a class of closed systems such methods offer a gold standard against which less formal approaches can be measured. For open systems -those which interact with the physical world- the task of obtaining the program specification can be as challenging as the task of deriving the program. And, when a system of this class must tolerate certain kinds of unreliability in the physical world, it is still more challenging to reach confidence that the specification obtained is adequate. We argue that widening the notion of software development to include specifying the behaviour of the relevant parts of the physical world gives a way to derive the specification of a control system and also to record precisely the assumptions being made about the world outside the computer.

A three dimensional surface measurement and reconstruction system for respiratory function analysis

Respiration is a complex activity. If the relationship between all neurological and skeletomuscular interactions was perfectly understood, an accurate dynamic model of the respiratory system could be developed and the interaction between different inputs and outputs could be investigated in a straightforward fashion. Unfortunately, this is not the case and does not appear to be viable at this time. In addition, the provision of appropriate sensor signals for such a model would be a considerable invasive task. Useful quantitative information with respect to respiratory performance can be gained from non-invasive monitoring of chest and abdomen motion. Currently available devices are not well suited in application for spirometric measurement for ambulatory monitoring. A sensor matrix measurement technique is investigated to identify suitable sensing elements with which to base an upper body surface measurement device that monitors respiration. This thesis is divided into two main areas of investigation; model based and geometrical based surface plethysmography. In the first instance, chapter 2 deals with an array of tactile sensors that are used as progression of existing and previously investigated volumetric measurement schemes based on models of respiration. Chapter 3 details a non-model based geometrical approach to surface (and hence volumetric) profile measurement. Later sections of the thesis concentrate upon the development of a functioning prototype sensor array. To broaden the application area the study has been conducted as it would be fore a generically configured sensor array. In experimental form the system performance on group estimation compares favourably with existing system on volumetric performance. In addition provides continuous transient measurement of respiratory motion within an acceptable accuracy using approximately 20 sensing elements. Because of the potential size and complexity of the system it is possible to deploy it as a fully mobile ambulatory monitoring device, which may be used outside of the laboratory. It provides a means by which to isolate coupled physiological functions and thus allows individual contributions to be analysed separately. Thus facilitating greater understanding of respiratory physiology and diagnostic capabilities. The outcome of the study is the basis for a three-dimensional surface contour sensing system that is suitable for respiratory function monitoring and has the prospect with future development to be incorporated into a garment based clinical tool.

A systems approach to public sector budgeting: the case of the planning, programming, budgeting system for the health and personal social services

The aim of this thesis is to examine the specific contextual factors affecting the applicability and development of the planning, programming, budgeting system (P.P.B.S.) as a systems approach to public sector budgeting. The concept of P.P.B.S. as a systems approach to public sector budgeting will first be developed and the preliminary hypothesis that general contextual factors may be classified under political, structural and cognitive headings will be put forward. This preliminary hypothesis will be developed and refined using American and early British experience. The refined hypothesis will then be tested in detail in the case of the English health and personal social services (H.P.S.S.), The reasons for this focus are that it is the most recent, the sole remaining, and the most significant example in British central government outside of defence, and is fairly representative of non-defence government programme areas. The method of data collection relies on the examination of unpublished and difficult to obtain central government, health and local authority documents, and interviews with senior civil servants and public officials. The conclusion will be that the political constraints on, or factors affecting P.P.B.S., vary with product characteristics and cultural imperatives on pluralistic decision-making; that structural constraints vary with the degree of coincidence of programme and organisation structure and with the degree of controllability of the organisation; and finally, that cognitive constraints vary according to product characteristics, organisational responsibilities, and analytical effort.