Cyclin G2 inhibits epithelial-to-mesenchymal transition by disrupting Wnt/ß-catenin signaling.

Epithelial ovarian cancer (EOC) has the highest mortality rate among gynecological malignancies owing to poor screening methods, non-specific symptoms and limited knowledge of the cellular targets that contribute to the disease. Cyclin G2 is an unconventional cyclin that acts to oppose cell cycle progression. Dysregulation of the cyclin G2 gene (CCNG2) in a variety of human cancers has been reported; however, the role of cyclin G2 in tumorigenesis remains unclear. In this study, we investigated the function of cyclin G2 in EOC. In vitro and in vivo studies using several EOC-derived tumor cell lines revealed that cyclin G2 inhibited cell proliferation, migration, invasion and spheroid formation, as well as tumor formation and invasion. By interrogating cDNA microarray data sets, we found that CCGN2 mRNA is reduced in several large cohorts of human ovarian carcinoma when compared with normal ovarian surface epithelium or borderline tumors of the ovary. Mechanistically, cyclin G2 was found to suppress epithelial-to-mesenchymal transition (EMT), as demonstrated by the differential regulation of various EMT genes, such as Snail, Slug, vimentin and E-cadherin. Moreover, cyclin G2 potently suppressed the Wnt/ß-catenin signaling pathway by downregulating key Wnt components, namely LRP6, DVL2 and ß-catenin, which could be linked to inhibition of EMT. Taken together, our novel findings demonstrate that cyclin G2 has potent tumor-suppressive effects in EOCs by inhibiting EMT through attenuating Wnt/ß-catenin signaling.

The western australian road injury database (1987-1996): ten years of linked police, hospital and death records of road crashes and injuries.

Accurate information about injuries and their causes is essential to road safety research, policy development and evaluation. Such information is most powerful when it is available for all road crashes within a jurisdiction. The Western Australian Road Injury Database achieves this through the on-going linkage of crash details from reports to police with the details of injuries to casualties contained in hospital and death records. Over the 10-year period 1987-1996, 386,132 road crashes involving 142,308 casualties were reported to the police in Western Australia. There were also 47,757 hospital discharge records and 2,906 death records related to road crashes during this period. Of the 142,308 police casualties, 17 848 had a matching hospital discharge record and 2,454 had a matching death registration. Linkage within the hospital records revealed that the 47,757 discharge records involved 43,179 individuals, of whom 39,073 were admitted to hospital once, 3,653 were admitted twice, 374 were admitted three times and 78 were admitted more than three times. Of the 43,179 hospitalised casualties, 817 had a matching death record. Linked police, hospital and death records of road crash casualties provide accurate outcome information for casualties in crashes reported to the police. In addition, estimates of under reporting of crashes for different road user groups can be made by comparing hospital records with and without a matching police record. This article demonstrates the power of a linked system to answer complex research questions related to outcome and under-reporting.

A linkage study of Western Australian drink driving arrests and road crash records.

Records of drivers in all reported road crashes occurring in Western Australia between 1987 and 1995 were linked with records of all drink driving arrests in the same period. About 7% of all drink driving arrests occurred because of a road crash. Differences were observed between these drink-driving crashes and other types of road crashes. Drink driving crashes tended to be more severe than those not involving alcohol. Serious crashes (involving fatalities or hospitalisations) accounted for 20% of alcohol-related crashes, but only 6% of all crashes reported over the study period. From another perspective, crash-related drink-driving arrests were more likely than routine enforcement arrests to involve younger (18-35 years) and older (65 years and over) drink drivers. Routine enforcement arrests, on the other hand, were likely to involve a greater proportion of Aboriginal drivers.

Novice drink drivers, recidivism and crash involvement.

A group of drink drivers with no prior arrest for drink driving was selected from drink driving arrest records originating in Western Australia between 1987 and 1995. These drink-driving records were linked to road crash records for the same period. The analysis of these combined records focussed on the sequence of driving events (i.e., arrests, crashes and arrests resulting from crashes) and the present article explores the relationship in time between known drink driving incidents and crash involvement. Using multi-variate survival analysis, it was found that if a driver's first drink driving offence resulted from a road crash, especially if this occurred at a younger age, he/she was significantly more likely to drink, drive and crash again.

Complementing police road-crash records with trauma registry data--an initial evaluation.

This paper examines the consistency of hospital and police reporting of outcomes of road traffic crashes using a database of linked police crash reports and trauma registry records. Criteria for inclusion into the trauma registry include trauma-related causes with subsequent stay of more than 24 h or death due to injuries. During the 1997 calendar year there were 497 cases of road-related injuries within the combined trauma registry of Sir Charles Gairdner and Fremantle Hospitals, of which only 82% had matching police records. Linkage rates were associated with gender, injury severity and the number of vehicles involved. Within the road user category, pedestrians were least likely to link. Of the linked records, police classification of injury severity was correct in 78% of cases. Male casualties were more likely to be correctly classified than females, after adjustment for related variables including injury severity. Correct classification of injury by police was also closely related to severity of injury. Identification and targeting of these groups of casualties is vital in refining the road-crash reporting system. Increased crash reporting and availability of data from these two sources will provide road authorities with more reliable measures of injury outcome.

Surrogacy: an Illinois policy conceived.

It is predictable that the precipitous decline in the number of available children for adoption will find many Illinois couples pursuing the surrogate route, as has happened in other states. The current uncertain status of Illinois law regarding surrogate contracts demands legislative focus and direction. To prevent protracted litigation as in other jurisdictions and to prevent injustices to those involved in the surrogate argument, "what we do, let us do quickly."

Stress nuclear myocardial perfusion imaging versus stress echocardiography: prognostic comparisons.

The use of noninvasive stress cardiac imaging for stratifying risk in patients with known or suspected coronary artery disease is growing as a tool for identification of the subgroup most likely to benefit from the expense and risk of more invasive procedures, including cardiac catheterization and coronary revascularization. In this setting, it is especially important that a test be able to identify patients with sufficiently low risk that clinicians are comfortable in deferring such interventions, especially in those with other markers of increased risk. Previous data have shown that cardiac risk is most closely related to the presence and extent of jeopardized viable myocardium on noninvasive stress cardiac imaging. Although stress echocardiography may have comparable ability to detect coronary artery disease, current data suggest that stress echocardiography detects significantly less jeopardized viable myocardium than stress nuclear myocardial perfusion imaging and consequently fewer patients at risk for cardiac events. Stress nuclear myocardial perfusion imaging may therefore have important advantages for risk stratification and the direction of future care of patients with known or suspected coronary artery disease.

Age related changes in drivers' crash risk and crash type.

Age and gender differences in the rates of crash involvement of Western Australian drivers were examined using the Road Injury Database of the Road Accident Prevention Research Unit at the University of Western Australia. The population examined was all drivers of cars, station wagons and related vehicles involved in property damage, injury and fatal crashes reported to the police in Western Australia from 1 January 1989 to 31 December 1992. It was found that drivers aged < 25 years were involved in ca 35% of crashes, compared with 3% for drivers 70 years and over. Drivers under 25 years had the highest rates on a population and licence basis, but when the distance travelled was taken into account, rates of crash involvement for the 75 or more age group were as high as those of the youngest age group. Females had higher rates of crash involvement than males in all age groups. Drivers over 70 years were involved in relatively more crashes involving fatalities and hospital admissions than younger drivers, although the number of such crashes was small. The youngest groups of drivers had proportionately more single vehicle crashes, drivers 30-59 years had more same direction crashes, and drivers over 60 years, particularly those over 75 years, had more direct and indirect right angle crashes. There were also age related patterns in the movements associated with these crashes. Drivers under 30 years were associated with swerving and swinging wide, drivers 30-59 years were stopped at the time of the crash disproportionately often, and drivers over 60 years were associated with turning movements. The percentage of crashes in daylight ranged from ca 64% for drivers under 20 years to a maximum of over 90% for those 80 years and over. These patterns are consistent with changes in exposure to risk of crash involvement with age, and also with changes in ability, experience and psychological function, which are also related to age.

Comparison of accident and emergency with police road injury data.

This paper examines the consistency of police and hospital reporting of outcomes of road traffic crashes using a database of linked police crash reports and accident and emergency department data. The database used consisted of linked records of road traffic crashes in Western Australia for the period of October 1, 1987 to December 31, 1988 from police reported casualty crashes, the discharge records from all hospital admissions in Western Australia, the Registrar-General's death records, and records for each ambulance trip as a result of a road crash in the metropolitan area of Perth. The results suggest that police records of hospital admissions from the group of accident and emergency attendances underestimated the total by approximately 15%.

An evaluation of road crash injury severity measures.

Reliable and consistent measures of injury severity are necessary for the study of environmental, crash and personal factors involved in road traffic crashes. This study was designed to evaluate measures of injury severity derived from computerized hospital discharge records, using 3609 road crash casualties admitted to hospital in Western Australia in 1988. External cause of injury codes were used to identify injuries from road traffic crashes. The ICDMAP software was used to convert the diagnosis codes into Abbreviated Injury Scale (AIS) scores for each body region. The maximum AIS values were derived using (1) all 12 diagnosis codes; (2) the first six diagnosis codes; and (3) the principal diagnosis code alone. Other measures of injury severity evaluated were the number of body regions with at least one injury; the number of regions with Abbreviated Injury Severity score of three or more; and total number of days spent in hospital. Discriminant analysis suggested that the AIS could be separated into minor and major injuries at a score of three and the Injury Severity Score at a score of nine. The measures derived from the AIS were all strongly correlated with each other and with the length of hospital stay and the dichotomized values gave similar results to the other scores when used in regression analyses of the injury experience of different types of road users. It was concluded that measures incorporating elements of both severity and number of injuries were preferable but length of hospital stay would be a suitable proxy if no other injury information was available.

The feasibility of linking hospital and police road crash casualty records without names.

Government and other agencies routinely collect complementary information on road crash casualties and there may be opportunities to widen the scope of data available for research and policy evaluation if mechanisms can be established to combine these data sources. Where unit record data are available, direct links within and between individual records can often be achieved using record linkage techniques. Without the benefit of unique identifiers, sufficient other identifying information such as the full name, date of birth and sex of the casualty, their role in the crash and the date of the crash are required to enable correct links between individual records to be made. However, all these data items may not be available and it is therefore important to investigate the effect this may have on the quality and quantity of links between records. The research reported here used the hospital admission and police records from the Western Australian Road Injury Database, which had previously been linked using all the identifying characteristics mentioned above, special purpose software and comprehensive manual checking. This set of linked records were considered to be a "gold standard" which could be used to measure the quantity and quality of links produced using fewer identifying characteristics. Results from this process showed that about 90% of the original links could be identified when a phonetic code of the family name of the casualty was used with age, sex, road user type and crash date. However, only about 50% of the original links were found if linking was performed without using names or phonetic name codes.

Miniature dipole E-field probes for characterizing both phase and amplitude of microwave radiators for hyperthermia.

This paper describes a system for characterizing th electric field patterns of microwave radiators in lossy media, in particular, of those used in hyperthermia treatments for cancer therapy. We discuss the design, fabrication and testing of small, minimally-perturbing electric field probes which are capable of measuring both amplitude and phase. An appropriate test configuration for mapping field patterns radiating from hyperthermia applicators (antennae) also is described. The system was developed specifically for the evaluation of applicators centered at 434 MHz and 915 MHz.

Hospital inpatient costs resulting from road crashes in Western Australia.

The purpose of this study was to estimate the inpatient costs of road crashes in Western Australia, and to investigate factors relating to casualties and their injuries that affect the hospital costs resulting from road crashes. All road crash casualties who were injured severely enough to be hospitalised in Western Australia in 1988 were included. A casemix classification system was used to classify patients into diagnostic related groups. Hospital costs were assigned to individual patients on the basis of their diagnostic related group and length of hospital stay. The annual cost of hospital treatment for road crash casualties was estimated as $13.9 million, and 33 per cent of this was incurred by those with lower extremity injuries and 27 per cent by those with head injuries. Hospital costs per casualty ranged from an average of $1388 for those sustaining minor (Abbreviated Injury Scale severity score of 1 or 2) spinal injuries to $16,580 and $33,424, respectively, for those sustaining severe (Abbreviated Injury Scale severity score of 4 or 5) head and spinal injuries. A multivariate analysis of variance revealed the following factors as having a significant independent effect on the hospital inpatient costs of road crash casualties: type of hospital (teaching or nonteaching), body region of injury, injury severity level and road user group. There were also significant interaction effects between different factors. Since hospital inpatient costs vary considerably across factors, using average cost data in the specific economic evaluation of road safety interventions for groups of road users is inappropriate.

A comparison of hospital and police road injury data.

In order to gather as much information as possible on road crashes and outcomes, routinely collected police reports of traffic accidents and hospital discharge files were individually matched or "linked" using a computerised iterative procedure on name-identified data from both sources. The two groups of linked and unlinked hospital records were compared. Within the linked dataset, a comparison of like variables was made and showed good agreement between the two sources on accident type and road user type. However, police-reported levels of injury severity were shown to be less reliable. In addition, the proportion of hospital inpatient records that linked to a police record was found to be influenced by several factors. The overall linkage rate from hospital to police was 64% but varied from 29% for motorcyclists in single-vehicle accidents to 79% for motor vehicle drivers. The linkage rate increased with increasing levels of injury severity and was substantially lower for casualties of certain ethnic groups. It was deduced that for most instances where a hospital record did not link to a police record, the crash had not been reported. These findings confirm that there was considerable underreporting of hospitalised road casualties to the police and that the extent of underreporting was greater for those less severely injured.

The construction of a road injury database.

In order to effectively examine possible causes and determinants of road trauma, reliable information on the participants, circumstances, and resultant injuries and deaths must be available. Characteristics of participants (persons and vehicles) and the circumstances of road accidents are routinely collected by police and road authorities, whereas details of the injuries and medical care provided to casualties are collected by hospital and ambulance services. A road injury database, linking data collected by the Health, Police, and Main Roads Departments of the Government of Western Australia with records of the St. John Ambulance Association and the Death Register, has been established. This paper describes the procedures used to link the various sources of data and discusses the design, construction, and quality of the resultant relational database.

Molecular cloning and characterization of a 42-kDa protein phosphatase of Leishmania chagasi.

Using rabbit serum raised against a potent T cell-stimulating antigen fraction of Leishmania chagasi promastigotes, we have cloned and expressed the Leishmania type 2C serine/threonine protein phosphatase, LcPP2C. LcPP2C was shown to be present as a 42-kDa protein in both the infective promastigote and tissue amastigote stages of L. chagasi and Leishmania amazonensis. DNA hybridization studies established the close conservation of LcPP2C among eight of eight geographically diverse species of Leishmania which cause a spectrum of human diseases. To support the relationship between LcPP2C and mammalian type 2C protein phosphatases observed through predicted amino acid sequence comparisons, we expressed enzymatically active rLcPP2C in Escherichia coli. We demonstrated that purified rLcPP2C readily dephosphorylated [32P]casein, an activity dependent on Mg2+ and insensitive to okadaic acid. In agreement with studies of rat liver PP2C, activity was maintained when Mg+2 was replaced with Mn+2 but not with Ca2+. As these parameters are characteristic of the eukaryotic type 2C serine/threonine protein phosphatases, LcPP2C can be classified as a member of this protein family. We further showed that of the four major classes of eukaryotic serine/threonine protein phosphatases, PP2C-and PP1-like activities, are readily detectable in Leishmania.

Effect of nutrition status and other factors on length of hospital stay after major gastrointestinal surgery.

Various factors may prolong postoperative recovery and the length of stay (LOS) in the hospital. In a retrospective study of 245 adult patients who had no oral intake for 5 days after major gastrointestinal surgery, we used a correlation matrix to describe the population and determine the effects of the following factors on LOS: malnutrition, complication status, stress level, type of surgery, pathology, period of inadequate nutrient intake, and use of nutritional support. LOS was markedly prolonged in malnourished patients compared with those who were not (23.5 +/- 16.5 vs. 16.5 +/- 10.7 days, means +/- SD, p < 0.001). Patients were then grouped into those who had nutritional support and those who had not, and a nutrition classification was derived by examining the uncertainty (entropy) in the data matrix that allowed separation of the population into distinct groups. Nutrition and complication status and days without oral nutrient intake were discriminative. Analysis of variance and multivariate studies were also used to determine whether the presence of malnutrition, complications, both together, or neither could predict LOS and to determine the confounding effect of nutritional support on LOS. A significantly extended LOS persisted for patients with malnutrition or complications and was most prolonged for those with both, but patients who received nutritional support had a greater LOS than those who did not. In addition to the effects of nutritional support, malnutrition, and complication status, LOS correlated with the duration of the postoperative period without oral nutrient intake. We therefore recommend systematic and early nutritional intervention for selected gastrointestinal surgical patients.