Using online tools at the Bovine Genome Database to manually annotate genes in the new reference genome.

With the availability of a new highly contiguous Bos taurus reference genome assembly (ARS-UCD1.2), it is the opportune time to upgrade the bovine gene set by seeking input from researchers. Furthermore, advances in graphical genome annotation tools now make it possible for researchers to leverage sequence data generated with the latest technologies to collaboratively curate genes. For many years the Bovine Genome Database (BGD) has provided tools such as the Apollo genome annotation editor to support manual bovine gene curation. The goal of this paper is to explain the reasoning behind the decisions made in the manual gene curation process while providing examples using the existing BGD tools. We will describe the sources of gene annotation evidence provided at the BGD, including RNA-seq and Iso-Seq data. We will also explain how to interpret various data visualizations when curating gene models, and will demonstrate the value of manual gene annotation. The process described here can be applied to manual gene curation for other species with similar tools. With a better understanding of manual gene annotation, researchers will be encouraged to edit gene models and contribute to the enhancement of livestock gene sets.

A critical review of the causes of death among post-mortem toxicological investigations: analysis of 34 buprenorphine-associated and 35 methadone-associated deaths.

AIMS: To assess the trends in the number, mortality and the nature of forensic cases involving toxicological detection of buprenorphine or methadone among toxicological investigations performed in Paris from June 1997 to June 2002. DESIGN: Retrospective, 5 year study with review of premortem data, autopsy, police reports, hospital data, and post-mortem toxicological analyses. SETTING AND PARTICIPANTS: 34 forensic cases of buprenorphine and 35 forensic cases of methadone detection among 1600 toxicological investigations performed at the Laboratory of Toxicology in the Medical Examiner's Office in Paris. MEASUREMENTS AND RESULTS: Therapeutic, toxic or lethal drug concentrations were defined based upon the results of blood analyses and the published literature. Drug concentrations were cross-referenced with other available ante- and post-mortem data. Subsequently, we classified a 'clear responsibility', 'possible responsibility' or 'not causative' role for buprenorphine or methadone in the death process, or 'no explanation of death'. Buprenorphine and methadone can be regarded as being directly implicated in, respectively, four of 34 death cases (12%) and three of 35 death cases (9%), and their participation in the lethal process is strongly plausible in eight (buprenorphine) and 11 (methadone) additional deaths. CONCLUSIONS: Analysis of causes of death reveals the difficulties in determining the role of substitution drugs in the death process, as many other factors may be involved, including circumstances surrounding death, past history, differential selection of subjects into either substitution modality and concomitant intake of other drugs (especially benzodiazepines and neuroleptics). The potential for synergistic or additive actions by other isolated molecules-particularly opioids, benzodiazepines, other psychotropes and alcohol-must be also considered.

Trends in opiate and opioid poisonings in addicts in north-east Paris and suburbs, 1995-99.

AIMS: (1). To assess the trends in the number, mortality and the nature of severe opiate/opioid poisonings from 1995 to 1999 in north-east Paris and adjacent suburbs and (2). to examine the effects of the introduction of high-dose buprenorphine on these parameters. DESIGN: Retrospective, 5-year study with review of pre-hospital, hospital and post-mortem data. SETTING AND PARTICIPANTS: Eighty patients from the toxicological intensive care unit (TICU) in north-east Paris, 421 patients from the pre-hospital emergency medical service in a north-east suburb of Paris (SAMU 93) and 40 deaths from the coroner's office in Paris. MEASUREMENTS AND RESULTS: We found that the number of pre-hospital opiate/opioid poisonings and deaths decreased over 5 years. During the same time frame, opiate/opioid poisoning admissions to our TICU remained steady, but the number of deaths declined. From 1995 to 1999, the detection of buprenorphine among opiate/opioid-poisoned TICU patients increased from two to eight occurrences per year while detection of opiates diminished from 17 to 10 occurrences per year. Increased buprenorphine detection correlated directly with increasing sales over this time period. In spite of the increased use of buprenorphine, the mortality associated with opiate/opioid poisonings has diminished in the pre-hospital environment from 9% in 1995 to 0% in 1999, and in the TICU from 12% in 1995 to 0% in 1997 and thereafter. We found a high frequency of multiple opiate/opioid use in severe poisonings, as well as the frequent association of other psychoactive drugs including ethanol. CONCLUSIONS: The number and the mortality of opiate/opioid poisonings appear to be stable or decreasing in our region. The association of multiple opiates/ opioids appears nearly as common as the association with other psychoactive drugs. The introduction of high-dose buprenorphine coincides with a decrease in opiate/opioid poisoning mortality. Further study will be necessary to clarify this observation.

Evaluation of the role of surgery in 130 patients with neuroblastoma.

The role of surgery for children with neuroblastoma was evaluated by using a recently proposed TNM staging system. One-hundred thirty patients were retrospectively assigned a TNM clinical stage (CS) preoperatively and a pathologic stage (PS) postoperatively. Patients with CS 4 were separated into CS 4A and CS 4B according to their age and pattern of metastases. Patient survival was analyzed according to CS, age, location of primary, and PS. Actuarial survival of patients was as follows: CS 1, 100%; CS 2, 82%; CS 3, 63%; CS 4A, 50%; and CS 4B, 5%. For all stages, patients younger than 1 year old survived longer than those older than 1 year (72% v 32%). Prognosis for CS 1 was the same regardless of age. For CS 2 and CS 3, patients younger than 1 year old lived longer. CS 4A had better survival than CS 4B. Survival by site was 100% for cervical, 62% for mediastinal, 45% for pelvic, and 36% for retroperitoneal primaries. The role of surgery was evaluated by analyzing survival according to the postoperative PS. PS 1-2-3 A were regarded as satisfactory resections since all macroscopic tumor was removed. PS 3B as a debulking procedure, and PS 3C as an unresectable lesion which was biopsied. Patients with nonmetastatic disease (CS 1-3) with PS 1 and PS 2 disease had a 100% survival rate; PS 3A, 93%; PS 3B, 58%; and PS 3C, 21%. This proves the value of total resection in nonmetastatic disease. The role of surgery could also be proven in metastatic disease.(ABSTRACT TRUNCATED AT 250 WORDS)

[Portal hypertension. Choice of therapy for children under 10 years: shunt or palliative surgery?]. / Hypertension portale. Choix de l'indication thérapeutique chez l'enfant de moins de 10 ans: dérivation ou palliatif.

Over the last 17 years, 65 cases of portal hypertension have been treated. Major surgery (shunt or disconnection) was performed in 22 children, 7 of these operations being conducted over the last two years by employing two recently developed techniques (Warren's selective distal splenorenal shunt, and Sugiura's wide azygoportal disconnection).

An epidemic of a "new" haemorrhagic disease in infants attributable to talcum powder contaminated with warfarin in Ho-Chi-Minh Ville (Vietnam).

In August 1981, pediatric hospitals in Ho-Chi-Minh Ville (Saigon) began to report numerous cases of a haemorrhagic syndrome in infants. A collaborative study with a French epidemilogist began on September 24, 1981, with the aim of finding the cause of this "new" haemorrhagic disease. After having excluded the hypothesis of a viral or bacterial infection, a retrospective study, using questionnaires with 83 items, concerning products of hygiene and nutrition and living conditions, was undertaken. This epidemiological investigation showed this phenomenon was caused by an anticoagulant contained in talcum powder. Analysis of the talcum powders found warfarin; the concentrations ranged between 1.7% and 6.5%. This dramatic episode (741 cases with 177 deaths) ended when the contaminated talc was withdrawn from circulation. The hypothesis of accidental contamination or use of warfarin in lieu of a perfuming agent must be rejected. Accidental addition of a rat-killer seems highly improbable and the possibility of intentional and malevolent adulteration is now under study. An experimental study of hemostasis in two baboons was carried out, using dermal application of the contaminated talc powder. The intoxicated animal died on the 5th day with severe vitamin K deficiency. This accident together with the animal study, shows the transcutaneous uptake of the anticoagulant, which could be of considerable importance in toxicology and in pharmacokinetics.

Epidemic of haemorrhagic disease in Vietnamese infants caused by warfarin-contaminated talcs.

In August, 1981, paediatric hospitals in Ho Chi Minh City (formerly Saigon), Vietnam, began to report cases of a haemorrhagic syndrome in infants. The cause of this haemorrhagic phenomenon was identified as talcum powder contaminated with the anticoagulant warfarin. Analysis of talcum powders revealed warfarin in concentrations between 1.7% and 6.5%. 741 cases were detected and 177 patients died. The possibility of accidental contamination or substitution of a perfuming agent by warfarin can be rejected. In an experiment with two baboons, the animal exposed to the contaminated talc died five days later from haemorrhage. The accident and the animal study demonstrate the significant transcutaneous uptake of the anticoagulant.