Point Process Methodology for On-line Spatio-temporal Disease Surveillance

The AEGISS (Ascertainment and Enhancement of Gastrointestinal Infection Surveillance and Statistics) project aims to use spatio-temporal statistical methods to identify anomalies in the space-time distribution of non-specific, gastrointestinal infections in the UK, using the Southampton area in southern England as a test-case. In this paper, we use the AEGISS project to illustrate how spatio-temporal point process methodology can be used in the development of a rapid-response, spatial surveillance system. Current surveillance of gastroenteric disease in the UK relies on general practitioners reporting cases of suspected food-poisoning through a statutory notification scheme, voluntary laboratory reports of the isolation of gastrointestinal pathogens and standard reports of general outbreaks of infectious intestinal disease by public health and environmental health authorities. However, most statutory notifications are made only after a laboratory reports the isolation of a gastrointestinal pathogen. As a result, detection is delayed and the ability to react to an emerging outbreak is reduced. For more detailed discussion, see Diggle et al. (2003). A new and potentially valuable source of data on the incidence of non-specific gastro-enteric infections in the UK is NHS Direct, a 24-hour phone-in clinical advice service. NHS Direct data are less likely than reports by general practitioners to suffer from spatially and temporally localized inconsistencies in reporting rates. Also, reporting delays by patients are likely to be reduced, as no appointments are needed. Against this, NHS Direct data sacrifice specificity. Each call to NHS Direct is classified only according to the general pattern of reported symptoms (Cooper et al, 2003). The current paper focuses on the use of spatio-temporal statistical analysis for early detection of unexplained variation in the spatio-temporal incidence of non-specific gastroenteric symptoms, as reported to NHS Direct. Section 2 describes our statistical formulation of this problem, the nature of the available data and our approach to predictive inference. Section 3 describes the stochastic model. Section 4 gives the results of fitting the model to NHS Direct data. Section 5 shows how the model is used for spatio-temporal prediction. The paper concludes with a short discussion.

The association between life events and suicide intent in self-poisoners with and without a history of deliberate self-harm: a preliminary study

The associations between life events in the 12 months preceding an episode of self-poisoning resulting in hospital attendance (the index episode), and the suicide intent of this episode were compared in individuals for whom the index episode was their first, episode and in individuals in whom it was a recurrence of DSH. Results indicated a significant interaction between independent life events, repetition status, and gender in the prediction of suicide intent, the association between life events and intent being moderated by repetition status in women only. The results provide preliminary evidence to suggest the presence of a suicidal process in women, in which the impact of negative life events on suicide intent diminishes across episodes.

"Death may come on like a stroke of lightening ..." : Phenomenological and morphological aspects of fatalities caused by manure gas

Due to the decomposition of biological material, hydrogen sulphide (H(2)S) is produced. In low concentrations, the well-known smell of "rotten eggs" is associated with H(2)S. In higher concentrations, H(2)S is an odourless and colourless gas that may cause rapid loss of consciousness, neurological and respiratory depression and imminent death-"... like a stroke of lightening". Hydrogen sulphide poisoning is an un-common incident that is often associated with colleague fatalities. In this study, 4 fatal accidents with 10 deceased victims are reported and the morphological and phenomenological aspects are presented. In these cases, the morphological findings, namely, discolouration of the livores, pulmonary pathologies and sub-mucosal or sub-serosal congestion bleeding were found in nearly all cases. Also the impending threat for colleagues, first aid helpers and professional rescue teams is demonstrated. The suspicion of a fatal H(2)S intoxication should be based on a precise scene analysis with respect to the possibility of life-threatening H(2)S intoxication for the helpers, the typical scent of rotten eggs, which may be noted on the corpses and the abovementioned morphological findings. The diagnosis should be confirmed by a qualitative and, if possible, quantitative analysis of H(2)S.

The Electroplating of Cadmium from Sulfate Solutions

It has been proven that cadmium forms a very satisfactory plate on steel, which has to withstand severe corrosion, especially the corrosion of sea water and spray. The metal is now successfully plated electrolytically from cyanide solutions, but wherever work is carried on with cyanide, there is great danger of poisoning to the workers.

Immune response of horses to vaccination with the recombinant Hc domain of botulinum neurotoxin types C and D

Botulinum neurotoxins, predominantly serotypes C and D, cause equine botulism through forage poisoning. The C-terminal part of the heavy chain of botulinum neurotoxin types C and D (HcBoNT/C and D) was expressed in Escherichia coli and evaluated as a recombinant mono- and bivalent vaccine in twelve horses in comparison to a commercially available toxoid vaccine. A three-dose subcutaneous immunization of adult horses elicited robust serum antibody response in an ELISA using the immunogen as a capture antigen. Immune sera showed dose-dependent high potency in neutralizing specifically the active BoNT/C and D in the mouse protection assay. The aluminium hydroxide based mono- and bivalent recombinant HcBoNT/C and D vaccines were characterized by good compatibility and the ability to elicit protective antibody titers similar or superior to the commercially available toxoid vaccine.

Factors that trigger emergency physicians to contact a poison centre: findings from a Swiss study.

OBJECTIVE Poison centres offer rapid and comprehensive support for emergency physicians managing poisoned patients. This study investigates institutional, case-specific and poisoning-specific factors which influence the decision of emergency physicians to contact a poison centre. METHODS Retrospective, consecutive review of all poisoning-related admissions to the emergency departments (EDs) of a primary care hospital and a university hospital-based tertiary referral centre during 2007. Corresponding poison centre consultations were extracted from the poison centre database. Data were matched and analysed by logistic regression and generalised linear mixed models. RESULTS 545 poisonings were treated in the participating EDs (350 (64.2%) in the tertiary care centre, 195 (35.8%) in the primary care hospital). The poison centre was consulted in 62 (11.4%) cases (38 (61.3%) by the tertiary care centre and 24 (38.7%) by the primary care hospital). Factors significantly associated with poison centre consultation included gender (female vs male) (OR 2.99; 95% CI 1.69 to 5.29; p<0.001), number of ingested substances (>1 vs 1) (OR 2.84; 95% CI 1.65 to 4.9; p<0.001) and situation (accidental vs intentional) (OR 2.76; 95% CI 1.05 to 7.25; p=0.039). In contrast, age, medical history and hospital size did not influence poison centre consultation. Poison centre consultation was significantly higher during the week, and significantly less during night shifts. The poison centre was consulted significantly more when patients were admitted to intensive care units (OR 5.81; 95% CI 3.25 to 10.37; p<0.001). Asymptomatic and severe versus mild cases were associated with more frequent consultation (OR 4.48; 95% CI 1.78 to 11.26; p=0.001 and OR 2.76; 95% CI 1.42 to 5.38; p=0.003). CONCLUSIONS We found low rates of poison centre consultation by emergency physicians. It appears that intensive care unit admission and other factors reflecting either complexity or uncertainty of the clinical situation are the strongest predictors for poison centre consultation. Hospital size did not influence referral behaviour.

Time-trends in assisted and unassisted suicides completed with different methods: Swiss National Cohort.

OBJECTIVE The number of suicides assisted by right-to-die associations has increased in recent years in Switzerland. The aim of our study was to compare time trends in rates of assisted and unassisted suicide from 1991-2008. METHODS The Swiss National Cohort is a longitudinal study of mortality in the Swiss population; based on linkage of census data with mortality records up to 2008. The Federal Statistical Office coded suspected assisted suicides from 1998 onwards; and from 2003 onwards right-to-die associations reported the suicides they assisted. We used Poisson regression to analyse trends in rates of suicide per 100'000 person-years, by gender and age groups (15-34, 35-64, 65-94 years). RESULTS A total of 7'940'297 individuals and 24'842 suicides were included. In women, rates changed little in the younger age groups but increased in 65-94-year-olds, due to an increase in suicide by poisoning (from 5.1 to 17.2 per 100'000; p <0.001). An increase in suicides by poisoning was also observed in older men (from 8.6 to 18.2; p<0.001). Most suicides by poisoning were assisted. In men, suicide rates declined in all age groups, driven by declines in suicide with firearms. CONCLUSIONS Research is needed to gain a better understanding of the reasons for the tripling of assisted suicide rates in older women, and the doubling of rates in older men, of attitudes and vulnerabilities of those choosing assisted suicide, and of access to palliative care. Rates of assisted suicide should be monitored; including data on patient characteristics and underlying comorbidities.

A survey of warning colours of pesticides

Pesticides are used to protect plants all over the world. Their increasing specificity has been due to utilization of differences in biochemical processes, and has been accompanied by lower human toxicity. Nevertheless cases of poisoning are still observed. While certain toxic substances are provided with characteristic dyes or pigments to facilitate easy identification, no overview of pesticide colors exists. The lack of available product information prompted us to explore the colors and dyes of pesticides registered in Germany, most of which are commercially available worldwide. A compilation of the colors and odors of 207 pesticide products is presented. While some of the substances can be identified by their physical characteristics, in other cases, the range of possibilities can be narrowed by their nature and color.

Pasteurization of Apple Cider with UV Irradiation

In a period of increasing concern about food safety, food poisoning outbreaks where unpasterurized apple cider or apple juice was found contaminated with Escherichia coli 0157:H7 reinforces the need for using the best technologies in apple cider production. Most apple cider is sold as an unpasteurized raw product. Because of their acidity, it was believed that juice products do not usually contain microorganisms such as E. coli 0157:H7, Salmonella, and Crytosporidium. Yet all of these foodborne pathogens are capable of being transmitted in unpasteurized juices. It is known that these pathogens can survive for several weeks in a variety of acidic juices. Although heat pasteurization is probably the best method to eliminate these pathogens, it is not the most desirable method as it changes sensory properties and also is very costly for small to mid-sized apple cider processors. Pasteurization of apple cider with Ultraviolet Irradiation (UV) is a potential alternative to heat pasteurization. Germicidal W irradiation is effective in inactivating microorganisms without producing undesirable by-products and changing sensory properties. Unpasteurized raw apple cider from a small local processor was purchased for this study. The effects of physical parameters, exposure time and dosage on the W treatment efficacy were examined as well as the effects of the UV light on apple cider quality. W light with principal energy at a wavelength of 254.7 nm, was effective in reducing bacteria (E .coli, ATCC 25922) inoculated apple cider. The W dosage absorbed by the apple cider was mathematically calculated. A radiation dose of 8,777 μW-s/cm2 reduced bacteria an average of 2.20 logs and in multiple passes, the FDA mandated 5-log reduction was achieved. Sensory analysis showed there was no significant difference between the W treated and non-treated cider. Experiments with W treated apple cider indicated a significant (p < 0.01) extension of product shelf life through inhibition of yeast and mold growth. The extension of the researched performed is applicable to other fruit juice processing operations.

Connecticut Poison Control Center. 2002 and 2003 Annual Report and Poison Exposure Statistics

The Connecticut Poison Control Center (CPCC) at the University of Connecticut Health Center (UCHC) was established in 1957 under Connecticut General Statute 10a- 132. The CPCC’s main responsibility is to provide 24-hour emergency toxicology management consultations for victims of poisoning, and serve as a source for pharmacology and toxicology-related information. The center monitors the epidemiology of human poisoning and provides surveillance for environmental and occupational chemical exposures, drug abuse, and pharmaceutical interactions and adverse effects. The CPCC performs toxicological research, and provides formal toxicology instruction for allied health professionals, as well as professional and consumer poison prevention education. The CPCC is one of 63 nationwide centers certified by the American Association of Poison Control Centers (AAPCC), and the only poison center in the state of Connecticut. The AAPCC establishes standards of care for poisoning and administers the Toxic Exposure Surveillance System (TESS), a national database of poisoning statistics, to which the CPCC is a contributor.

Los Voluntarios Abren les Puertas: las Cinco Claves para el Manejo Seguro del Plomo

Millions of houses and apartments built before 1978 have paint that contains lead. Chips, dust, and fumes from this paint can be very dangerous if they are not handled properly. Lead is particularly hazardous to unborn babies, infants, and young children. Volunteers in painting and housing-rehabilitation programs often work in homes that contain lead paint. The work they perform can create a lead hazard if they disturb this paint and produce paint chips or dust. Volunteers Opening Doors is a video program for these volunteers. It explains how volunteers can protect housing residents,themselves, and their families from lead poisoning by using the five keys to lead safety: 1. Protect residents and their belongings. 2. Prepare the work area. 3. Protect yourself from dust and debris. 4. Work wet. 5. Work clean.

Investigating the Role of Small, Acid-Soluble Spore Proteins (SASPs) in the Resistance of Clostridium Perfringens Spores to Heat.

BACKGROUND: Clostridium perfringens type A food poisoning is caused by enterotoxigenic C. perfringens type A isolates that typically possess high spore heat-resistance. The molecular basis for C. perfringens spore heat-resistance remains unknown. In the current study, we investigated the role of small, acid-soluble spore proteins (SASPs) in heat-resistance of spores produced by C. perfringens food poisoning isolates. RESULTS: Our current study demonstrated the presence of all three SASP-encoding genes (ssp1, 2 and 3) in five surveyed C. perfringens clinical food poisoning isolates. beta-Glucuronidase assay showed that these ssp genes are expressed specifically during sporulation. Consistent with these expression results, our study also demonstrated the production of SASPs by C. perfringens food poisoning isolates. When the heat sensitivities of spores produced by a ssp3 knock-out mutant of a C. perfringens food poisoning isolate was compared with that of spores of the wild-type strain, spores of the ssp3 mutant were found to exhibit a lower decimal reduction value (D value) at 100 degrees C than exhibited by the spores of wild-type strain. This effect was restored by complementing the ssp3 mutant with a recombinant plasmid carrying wild-type ssp3, suggesting that the observed differences in D values between spores of wild-type versus ssp3 mutant was due to the specific inactivation of ssp3. Furthermore, our DNA protection assay demonstrated that C. perfringens SASPs can protect DNA from DNase I digestion. CONCLUSION: The results from our current study provide evidences that SASPs produced by C. perfringens food poisoning isolates play a role in protecting their spores from heat-damage, which is highly significant and relevant from a food safety perspective. Further detailed studies on mechanism of action of SASPs from C. perfringens should help in understanding the mechanism of protection of C. perfringens spores from heat-damage.

Volunteers Opening Doors: the Five Keys to Lead Safety

Millions of houses and apartments built before 1978 have paint that contains lead. Chips, dust, and fumes from this paint can be very dangerous if they are not handled properly. Lead is particularly hazardous to unborn babies, infants, and young children. Volunteers in painting and housing-rehabilitation programs often work in homes that contain lead paint. The work they perform can create a lead hazard if they disturb this paint and produce paint chips or dust. Volunteers Opening Doors is a video program for these volunteers. It explains how volunteers can protect housing residents,themselves, and their families from lead poisoning by using the five keys to lead safety: 1. Protect residents and their belongings. 2. Prepare the work area. 3. Protect yourself from dust and debris. 4. Work wet. 5. Work clean.

RNA polymerase II large subunit degradation induced by ecteinascidin 743: Molecular characterization and subsequent rational investigation of antitumor mechanisms in cancers with clinical response

Ecteinascidin 743 (Et-743), which is a novel DNA minor groove alkylator with a unique spectrum of antitumor activity, is currently being evaluated in phase II/III clinical trials. Although the precise molecular mechanisms responsible for the observed antitumor activity are poorly understood, recent data suggests that post-translational modifications of RNA polymerase II Large Subunit (RNAPII LS) may play a central role in the cellular response to this promising anticancer agent. The stalling of an actively transcribing RNAPII LS at Et-743-DNA adducts is the initial cellular signal for transcription-coupled nucleotide excision repair (TC-NER). In this manner, Et-743 poisons TC-NER and produces DNA single strand breaks. Et-743 also inhibits the transcription and RNAPII LS-mediated expression of selected genes. Because the poisoning of TC-NER and transcription inhibition are critical components of the molecular response to Et-743 treatment, we have investigated if changes in RNAPII LS contribute to the disruption of these two cellular pathways. In addition, we have studied changes in RNAPII LS in two tumors for which clinical responses were reported in phase I/II clinical trials: renal cell carcinoma and Ewing's sarcoma. Our results demonstrate that Et-743 induces degradation of the RNAPII LS that is dependent on active transcription, a functional 26S proteasome, and requires functional TC-NER, but not global genome repair. Additionally, we have provided the first experimental data indicating that degradation of RNAPII LS might lead to the inhibition of activated gene transcription. A set of studies performed in isogenic renal carcinoma cells deficient in von Hippel-Lindau protein, which is a ubiquitin-E3-ligase for RNAPII LS, confirmed the central role of RNAPII LS degradation in the sensitivity to Et-743. Finally, we have shown that RNAPII LS is also degraded in Ewing's sarcoma tumors following Et-743 treatment and provide data to suggest that this event plays a role in decreased expression of the Ewing's sarcoma oncoprotein, EWS-Fli1. Altogether, these data implicate degradation of RNAPII LS as a critical event following Et-743 exposure and suggest that the clinical activity observed in renal carcinoma and Ewing's sarcoma may be mediated by disruption of molecular pathways requiring a fully functional RNAPII LS. ^