Feasibility and acceptability of a remotely-delivered behavioural health coaching intervention to limit gestational weight gain.

INTRODUCTION: Gestational weight gain (GWG) and postpartum weight retention (PPWR) are significant, potentially modifiable, contributors to women's future weight and health trajectories. There is a need for feasible and patient-centered (i.e., convenient, remotely-delivered, technology-enhanced, and accessible through the prenatal care setting) behavioural interventions that limit GWG and PPWR. This study tests the feasibility and acceptability of a remotely-delivered behavioural health coaching intervention to limit gestational weight gain and postpartum weight retention. METHODS: Pregnant women (11-16 weeks gestation) were recruited from two prenatal clinics and randomized to the active intervention or health education comparison group. Completion of the program was monitored and perceived helpfulness was rated (0-100). RESULTS: Twenty-six women were randomized (n = 13 per arm; mean age = 31.6 years, SD = 3.6; mean BMI = 26.7 kg/m2, SD = 7.4). Participants completed a median of 18 coaching calls and 16/19 learning activities during pregnancy, and a median of 6 calls and 5/6 learning activities postpartum. They logged weights at least once/week for a median of 36/38 expected weeks and tracked daily calories and exercise for a median of 154/266 days and 72/266 days, respectively. Median (Q1, Q3) helpfulness ratings of the program during pregnancy were 80 (64, 91) and 62 (50, 81) postpartum; helpfulness ratings of coaching calls were 85 (58, 98). At 37 weeks gestation, 77% of participants achieved IOM weight gain recommendations compared to 54% in the comparison group. CONCLUSIONS: This study provides evidence for the feasibility and acceptability of a remotely-delivered behavioural weight control intervention in pregnancy and postpartum.

Treatment with abiraterone and enzalutamide does not overcome poor outcome from metastatic castration-resistant prostate cancer in men with the germline homozygous HSD3B1 c.1245C genotype.

BACKGROUND: In men with castration-sensitive prostate cancer (CSPC), the HSD3B1 c.1245A>C variant has been reported to be associated with shorter responses to first-line androgen-deprivation therapy (ADT). Here, we evaluated the association between the inherited HSD3B1 c.1245A>C variant and outcomes from metastatic castration-resistant prostate cancer (mCRPC) after first-line treatment with abiraterone (Abi) or enzalutamide (Enza). PATIENTS AND METHODS: Patients with mCRPC (n = 266) were enrolled from two centers at the time of starting first-line Abi/Enza. Outcomes after Abi/Enza included best prostate-specific antigen (PSA) response, treatment duration, and overall survival (OS). Outcomes after first-line ADT were determined retrospectively, and included treatment duration and OS. As was prespecified, we compared patients with the homozygous variant HSD3B1 genotype (CC genotype) versus the combined group with the heterozygous (AC) and homozygous wild-type (AA) genotypes. RESULTS: Among the 266 patients, 22 (8.3%) were homozygous for the HSD3B1 variant (CC). The CC genotype had no association with PSA response rate; the median Abi/Enza treatment duration was 7.1 months for the CC group and 10.3 months for the AA/AC group (log rank P = 0.34). Patients with the CC genotype had significantly worse OS, with median survival at 23.6 months for the CC group and 30.7 months for the AA/AC group (log rank P = 0.02). In multivariable analysis adjusting for age, Gleason score, PSA, prior chemotherapy, and M1 disease, the association between the CC genotype and OS remained significant (hazard ratio 1.78, 95% confidence interval 1.03-3.07, P = 0.04). Poor outcome after first-line ADT in the CC group was also observed when evaluating retrospective ADT duration data for the same combined cohort. CONCLUSIONS: In this large two-center study evaluating the HSD3B1 c.1245 genotype and outcomes after first-line Abi/Enza, homozygous variant (CC) HSD3B1 genotype was associated with worse outcomes. Novel therapeutic strategies are needed to enable treatment selection based on this genetic marker.

Evolution and characterisation of the AhRAF4 NB-ARC gene family induced by Aspergillus flavus inoculation and abiotic stresses in peanut.

Aflatoxin contamination in peanut is a serious food safety issue to human health around the world. Finding disease resistance genes is a key strategy for genetic improvement in breeding to deal with this issue. We identified an Aspergillus flavus-induced NBS-LRR gene, AhRAF4, using a microarray-based approach. By comparison of 23 sequences from three species using phytogenetics, protein secondary structure and three-dimensional structural analyses, AhRAF4 was revealed to be derived from Arachis duranensis by recombination, and has newly evolved into a family of several members, characterised by duplications and point mutations. However, the members of the family descended from A. ipaensis were lost following tetraploidisation. AhRAF4 was slightly up-regulated by low temperature, drought, salicylic acid and ethylene, but down-regulated by methyl jasmonate. The distinct responses upon As. flavus inoculation and the differential reactions between resistant and susceptible varieties indicate that AhRAF4 might play a role in defence responses. Temporal and spatial expression and the phenotype of transformed protoplasts suggest that AhRAF4 may also be associated with pericarp development. Because tetraploid cultivated peanuts are vulnerable to many pathogens, an exploration of R-genes may provide an effective method for genetic improvement of peanut cultivars.

Socio-economic benefits from protected areas in southeastern Australia.

International case studies of protected area performance increasingly report that conservation and socio-economic outcomes are interdependent. Effective conservation requires support and cooperation from local governments and communities, which in turn requires that protected areas contribute to the economic well-being of the communities in which they are sited. Despite increasing recognition of their importance, robust studies that document the socio-economic impacts of protected areas are rare, especially in the developed world context. We proposed 3 potential pathways through which protected areas might benefit local communities in the developed world: the improved local housing value, local business stimulus, and increased local funding pathways. We examined these pathways by undertaking a statistical longitudinal analysis of 110 regional and rural communities covering an area of approximately 600,000 km(2) in southeastern Australia. We compared trends in 10 socio-economic indicators describing employment, income, housing, business development and local government revenue from 2000 to 2010. New protected areas acquisitions led to an increased number of new dwelling approvals and associated developer contributions, increased local business numbers, and increased local government revenue from user-pays services and grants. Longer-term effects of established protected areas included increased local council revenue from a variety of sources. Our findings provide support for each of our 3 proposed benefit pathways and contribute new insights into the cycling of benefits from protected areas through the economy over time. The business and legislative models in our study are typical of those operating in many other developed countries; thus, the benefit pathways reported in our study are likely to be generalizable. By identifying and communicating socio-economic benefits from terrestrial protected areas in a developed world context, our findings represent an important step in securing local support and ongoing high-level protection for key components of the world's biodiversity.

The utilization of poisons information resources in Australasia.

PURPOSE: To identify poisons information resources most commonly utilized by Australasian Emergency Department staff, and examine attitudes regarding the benefits and user experience of the electronic products used. METHODS: A survey tool was mailed to six Emergency Departments each in New Zealand and Australia to be answered by medical and nursing staff. RESULTS: Eighty six (71.7%) responses were received from the 120 survey forms sent: 70 (81%) responders were medical staff, the remainder nursing. Electronic resources were the most accessed poisons information resource in New Zealand; Australians preferring discussion with a colleague; Poisons Information Centers were the least utilized resource in both countries. With regard to electronic resources, further differences were recognized between countries in: ease of access, ease of use, quality of information and quantity of information, with New Zealand better in all four themes. CONCLUSIONS: New Zealand ED staff favored electronic poisons information resources while Australians preferred discussion with a colleague. That Poisons Information Centers were the least utilized resource was surprising.

Repetitive scratching and noxious heat do not inhibit histamine-induced itch in atopic dermatitis.

BACKGROUND: Repetitive scratching is the most common behavioural response to itch in atopic dermatitis (AD). Patients with chronic itch often report that very hot showers inhibit itch. We recently reported that scratching and noxious heat stimuli inhibit histamine-induced itch in healthy subjects. However, no psychophysical studies have been performed in AD to assess the effects of repetitive heat pain stimuli and scratching on histamine-induced itch. OBJECTIVES: To examine the effects of repetitive noxious heat and scratching on itch intensity in patients with AD using quantitative sensory testing devices. METHODS: Itch was induced with histamine iontophoresis in 16 patients with AD in both lesional and nonlesional skin as well as in 10 healthy subjects. Repetitive noxious heat and scratching were applied 3 cm distal to the area of histamine iontophoresis. Subjects rated their perceived intensity of histamine-induced itch with a computerized visual analogue scale. RESULTS: Our results demonstrate that repetitive noxious heat and scratching do not inhibit itch intensity in lesional and nonlesional AD skin but do so in healthy skin. Of note, both these stimuli increase itch intensity in lesional AD skin. CONCLUSIONS: Our results strongly suggest that scratching and noxious thermal stimuli have a different effect upon histamine-induced itch perception in patients with AD when compared with healthy controls. This difference may be associated with both peripheral and central sensitization of nerve fibres in AD.

A randomised trial of two methods of issuing prenatal test results: the ARIA (Amniocentesis Results: Investigation of Anxiety) trial.

BACKGROUND: Many pregnant women experience anxiety while waiting for the results of diagnostic tests. Policies and practices intended to reduce this anxiety require evaluation. OBJECTIVES: To test the following two hypotheses: * That giving amniocentesis results out on a fixed date alters maternal anxiety during the waiting period, compared with a policy of telling parents that the result will be issued "when available" (i.e. variable date). * That issuing early results from a rapid molecular test alters maternal anxiety during the waiting period, compared with not receiving any results prior to the karyotype. The effects of the two interventions on anxiety 1 month after receiving karyotype results were also examined. DESIGN: A multicentre, randomised, controlled, open fixed sample, 2 x 2 factorial design trial, with equal randomisation. SETTING: The prenatal diagnosis clinics in 12 hospitals in England offering amniocentesis as a diagnostic test for Down's syndrome. SAMPLE: Two hundred and twenty-six women who had had an amniocentesis were randomised between June 2002 and July 2004. Eight women with abnormal results or test failure were excluded post-randomisation. INTERVENTIONS: Issuing karyotype results on a prespecified fixed date, rather than issuing them as soon as they became available. Issuing karyotype results alone, or subsequent to issuing results from a rapid molecular test for the most common chromosomal abnormalities. MAIN OUTCOME MEASURES: Average anxiety during the waiting period, calculated using daily scores from the short version of the Spielberger State-Trait Anxiety Inventory (STAI). Anxiety 1 month after receiving karyotype results, measured using the short form STAI. RESULTS: Issuing early results from a partial but rapid test reduced maternal anxiety by a clinically significant amount during the waiting period (mean daily score 12.5 versus 14.8; scale score difference -2.36, 95% CI -1.2, -3.6), compared with receiving only the full karyotype results. There was no evidence that giving out karyotype results on a fixed or on a variable date altered maternal anxiety during the waiting period (mean daily score 13.2 versus 14.2; scale score difference -1.02, 95% CI -2.2, 0.2). One month after receiving normal karyotype results, anxiety was low in all groups, but women who had been given rapid test results tended to be more anxious than those who had not (mean single day score 9.2 versus 8.3; mean scale score difference 0.95, 95% CI -0.03, 1.9). This small to moderate effect did not reach conventional levels of statistical significance. CONCLUSIONS: Rapid testing was a beneficial addition to karyotyping, at least in the short term. This does not necessarily imply that early results would be preferred to comprehensive ones if women had to choose between them. Because there are no clear advantages in anxiety terms of issuing karyotype results as soon as they become available, or on a fixed date, women could be given a choice between them.

Amniocentesis results: investigation of anxiety. The ARIA trial.

OBJECTIVES: The Amniocentesis Results: Investigation of Anxiety (ARIA) trial tested two hypotheses: first, that giving amniocentesis results out on a fixed date alters maternal anxiety during the waiting period, compared with a policy of telling parents that the result will be issued 'when available' (i.e. a variable date), and secondly, that issuing early results from a rapid molecular test alters maternal anxiety during the waiting period, compared with not receiving any results prior to the karyotype. The effects of the two interventions on anxiety 1 month after receiving karyotype results were also examined. DESIGN: A multi-centre, randomised, controlled, open fixed sample, 2 x 2 factorial design trial, with equal randomisation. SETTING: Twelve hospitals in England offering amniocentesis as a diagnostic test for Down's syndrome. PARTICIPANTS: A total of 226 women who had had an amniocentesis were randomised between June 2002 and July 2004. Eight women with abnormal results or test failure were excluded post-randomisation. INTERVENTIONS: Issuing karyotype results on a prespecified fixed date, rather than issuing them as soon as they became available and issuing karyotype results alone, or subsequent to issuing results from a rapid molecular test for the most common chromosomal abnormalities. MAIN OUTCOME MEASURES: Average anxiety during the waiting period, calculated using daily scores from the short version of the Spielberger State-Trait Anxiety Inventory (STAI). Recalled anxiety, measured 1 month after receiving karyotype results, using a rating scale. Anxiety at the 1-month follow-up, measured using the short-form STAI. RESULTS: There was no evidence that giving out karyotype results on a fixed or on a variable date altered maternal anxiety during the waiting period. However, the analysis only had sufficient power to detect a moderate to large effect. Issuing early results from a partial, but rapid, test reduced maternal anxiety during the waiting period, compared with receiving only the full karyotype results. This was a moderate to large effect. In addition, group differences in recalled anxiety reflected fairly closely the differences in anxiety women had experienced while waiting for results. One month after receiving normal karyotype results, anxiety was low in all groups, but women who had been given rapid test results were more anxious than those who had not. This was a small to moderate effect. CONCLUSIONS: Since there are no clear advantages in anxiety terms of issuing karyotype results as soon as they become available, or on a fixed date, women could be given a choice between them. Rapid testing was a beneficial addition to karyotyping, at least in the short term. This does not necessarily imply that early results would be preferred to comprehensive ones if women had to choose between them. There should be further research, including more qualitative studies, into the causes, characteristics and consequences of anxiety associated with prenatal testing. The effects of different testing regimes on short- and long-term anxiety, on the preferences of women and on the relationship between anxiety and preference should be investigated. More research is needed on the ways in which information might be used to minimise anxiety in different testing regimes. Further research is also required into the policy implications of incorporating individual preferences for different testing regimes into prenatal testing programmes.

EVALUATE hysterectomy trial: a multicentre randomised trial comparing abdominal, vaginal and laparoscopic methods of hysterectomy.

OBJECTIVES: To test the null hypothesis of no significant difference between laparoscopic hysterectomy (LH), abdominal hysterectomy (AH) and vaginal hysterectomy (VH) with regard to each of the outcome measures of the trial, and also to assess the cost-effectiveness of the alternatives. DESIGN: Patients were allocated to either the vaginal or abdominal trial by the individual surgeon according to their usual clinical practice. After allocation patients were then randomised to receive either LH or the default procedure in an unbalanced 2:1 manner. SETTING: Forty-three surgeons from 28 centres throughout the UK and two centres in South Africa took part in the study. PARTICIPANTS: Patients with gynaecological symptoms that, in the opinion of the gynaecologist and the patient, justified hysterectomy. INTERVENTIONS: Of 1380 patients recruited to the study, 876 were included in the AH trial and 504 in the VH trial. In the AH trial, 584 patients had a laparoscopic type of hysterectomy (designated ALH) and 292 had a standard AH. In the VH trial 336 had a VLH and 168 had a standard VH. A cost--utility analysis was undertaken based on a 1-year time horizon. Quality-adjusted life years (QALYs) were estimated using the EQ-5D. RESULTS: Compared with AH, LH was associated with a higher rate of major complications, less postoperative pain and shorter hospital stay, but took longer to perform. Securing the ovarian pedicles with laparoscopic sutures was used in only 7% of cases but was associated with 25% of the complications. At the 6 weeks postoperative point, ALH was associated with a significantly better physical component of the SF-12 (QoL questionnaire), better body image scale scores and a significantly increased frequency of sexual intercourse than AH. These differences were not observed at either 4 or 12 months after surgery. There were no significant differences in any measured outcome between LH and VH except that VLH took longer to perform and was associated with a higher rate of detecting unexpected pathology. Compared with VH, VLH had a higher mean cost per patient of GBP401 and higher mean QALYs of 0.0015, resulting in an incremental cost per QALY gained of GBP267,333. The probability that VLH is cost-effective was less than 50% for a large range of willingness to pay values for an additional QALY. Compared with AH, ALH had a higher mean cost per patient of GBP186 and higher mean QALYs of 0.007, resulting in an incremental cost per QALY gained of GBP26,571. CONCLUSIONS: ALH is associated with a significantly higher risk of major complications and takes longer to perform than AH. ALH is, however, associated with less pain, quicker recovery and better short-term QoL after surgery than AH. The cost-effectiveness of ALH is finely balanced and is also influenced by the choice of reusable versus disposable equipment. Individual surgeons must decide between patient-orientated benefits and the risk of severe complications. VLH was not cost-effective relative to VH. Recommendations for future research include the application and relevance of QoL measures following hysterectomy, and long-term follow-up; patient preferences; reducing complication rates; improving gynaecological surgical training; surgeon effect in surgery trials; care pathways for hysterectomy; additional pathology identification in LH and meta-analysis/further trial of VH versus LH.

PTEN inactivation is rare in melanoma tumours but occurs frequently in melanoma cell lines.

Deletions detected in cytogenetic and loss of heterozygosity (LOH) studies indicate that at least one tumour suppressor gene maps to the long arm of chromosome 10. Previous deletion mapping studies have observed LOH on 10q in about 30% of melanomas analysed. The PTEN gene, mapping to chromosome band 10q23.3, encodes a protein with both lipid and protein phosphatase activity. Somatic mutations and deletions in have been detected in a variety of cell lines and tumours, including melanoma samples. We performed mutation analyses and extensive allelic loss studies to investigate the role this gene plays in melanoma pathogenesis. We found that a total of 34 out of 57 (60%) melanoma cell lines carried hemizygous deletions of chromosome 10q encompassing the PTEN locus. A further three cell lines carried smaller deletions excluding PTEN. Inactivation of both PTEN alleles by exon-specific homozygous deletion or mutation was observed in 13 out of 57 (23%) melanoma cell lines. The mutation spectrum observed does not indicate an important role for ultraviolet radiation in the genesis of these mutations, and evidence from three cell lines supports the acquisition of PTEN aberrations in culture. Ten out of 49 (20%) matched melanoma tumour/normal samples harboured hemizygous deletions of either the whole chromosome or most of the long arm. Mutations within were detected in only one of the 10 tumours demonstrating LOH at 10q23 that were analysed. These results suggest that PTEN inactivation may be important for the propagation of melanoma cells in culture, and that another chromosome 10 tumour suppressor gene may be important for melanoma pathogenesis.

Contact allergy to corticosteroids in patients using inhaled or intranasal corticosteroids for allergic rhinitis or asthma.

BACKGROUND: Patients using topically applied corticosteroids are at risk of developing allergic contact hypersensitivity. OBJECTIVE: To assess prevalence of allergic contact hypersensitivity reactions to inhaled or intranasal corticosteroids. METHODS: A prospective study of 30 adult patients using inhaled or intranasal corticosteroids for conditions such as allergic rhinitis was performed. We used epicutaneous patch testing to determine the prevalence of allergic contact hypersensitivity to corticosteroids and common additives (propylene glycol and benzalkonium chloride) in inhaled and nasal corticosteroid preparations in this population. RESULTS: Of 30 patients, 4 (13%) had positive patch test results. 3 (10%) were allergic reactions and 1 (3%) was an irritant reaction. Half of the reactions were to a corticosteroid (budesonide) and half were to a common preservative in nasal preparations (benzalkonium chloride). CONCLUSION: This study supports other clinical evidence that contact dermatitis/mucositis from inhaled or intranasal corticosteroid products can occur. The corticosteroids or added agents such as preservatives can be causative and may result in allergic or irritant reactions, which can be relevant to clinical symptoms.

Effect of natural gas exsolution on specific storage in a confined aquifer undergoing water level decline.

The specific storage of a porous medium, a function of the compressibility of the aquifer material and the fluid within it, is essentially constant under normal hydrologic conditions. Gases dissolved in ground water can increase the effective specific storage of a confined aquifer, however, during water level declines. This causes a reduction in pore pressure that lowers the gas solubility and results in exsolution. The exsolved gas then displaces water from storage, and the specific storage increases because gas compressibility is typically much greater than that of water or aquifer material. This work describes the effective specific storage of a confined aquifer exsolving dissolved gas as a function of hydraulic head and the dimensionless Henry's law constant for the gas. This relation is applied in a transient simulation of ground water discharge from a confined aquifer system to a collapsed salt mine in the Genesee Valley in western New York. Results indicate that exsolution of gas significantly increased the effective specific storage in the aquifer system, thereby decreasing the water level drawdown.

Measuring met and unmet need of drug misusers: integration of quantitative and qualitative data.

This paper reports on the combination of qualitative and quantitative methods which were used to record the attitudes to, and perceptions of, drug treatment services by current, ex-, and potential clients in south-east London. Three research instruments were employed: a structured current client satisfaction survey (n = 333); a questionnaire which included open-ended questions, administered to drug users not currently in treatment (n = 88), and focus groups for young drug users not in treatment (n = 14), women in treatment (n = 7) and men in treatment (n = 11). The data thus collected were used to construct a picture of local met and unmet need and obstacles to the uptake of health care, which is supported by more than one perspective, and which can reasonably be used as the basis for the planning of local health care purchase. Three major concerns were revealed by the data: the inadequacy of existing GP drug services; the deterrent effect of long waiting lists for methadone treatment, and the role of treatment services in relation to those drug users who acknowledge that their drug use is problematic, but believe that treatment services have nothing to offer them.

Localization of multiple melanoma tumor-suppressor genes on chromosome 11 by use of homozygosity mapping-of-deletions analysis.

Loss-of-heterozygosity (LOH) studies have implicated one or more chromosome 11 tumor-suppressor gene(s) in the development of cutaneous melanoma as well as a variety of other forms of human cancer. In the present study, we have identified multiple independent critical regions on this chromosome by use of homozygosity mapping of deletions (HOMOD) analysis. This method of analysis involved the use of highly polymorphic microsatellite markers and statistics to identify regions of hemizygous deletion in unmatched melanoma cell line DNAs. Regions of loss were defined by the presence of an extended region of homozygosity (ERH) at > or =5 adjacent markers and having a statistical probability of < or =.001. Significant ERHs were similar in nature to deletions identified by LOH analyses performed on uncultured melanomas, although a higher frequency of loss (24 [60%] of 40 vs. 16 [34%] of 47) was observed in the cell lines. Overall, six small regions of overlapping deletions (SROs) were identified on chromosome 11 flanked by the markers D11S1338/D11S907 (11p13-15.5 [SRO1]), D11S1344/D11S11385 (11p11.2 [SRO2]), D11S917/D11S1886 (11q21-22.3 [SRO3]), D11S927/D11S4094 (11q23 [SRO4]), AFM210ve3/D11S990 (11q24 [SRO5]), and D11S1351/D11S4123 (11q24-25 [SRO6]). We propose that HOMOD analysis can be used as an adjunct to LOH analysis in the localization of tumor-suppressor genes.

Diversion of prescribed drugs by drug users in treatment: analysis of the UK market and new data from London.

AIMS: To review the available knowledge about the diversion to the illicit market of drugs prescribed to drug users in treatment in the United Kingdom, and to identify aspects of the London market in more detail. METHOD: An analysis of the literature and new data in terms of the extent and nature of the market, the practicalities of trade, motives for selling, reasons for demand and the influence of variations in prescribing practice on diversion. Prices of diverted prescription drugs and details of their availability in London are presented. FINDINGS: The size of the market is substantial and appears to involve a large number of individuals, each diverting small amounts of their own prescribed drugs. Major motives for selling prescribed drugs are to raise funds to buy other, preferred, drugs and/or to pay for a private prescription. Buyers in treatment appear to be motivated by a desire to supplement their own prescriptions because they are dissatisfied with the particular drug prescribed, dosage and formulation. Drug users in treatment can exploit the variations in prescribing practice--such as how much 'take-home' medication they are allowed and whether tests are conducted to ascertain if they are using it themselves--and divert their prescribed drugs. Prices of prescription drugs on the illicit market can fluctuate on a daily basis according to supply and demand. CONCLUSIONS: The results suggest that, to be effective, diversion control must simultaneously involve deterrents from prescribers, drug treatment services, law enforcement agencies and dispensing pharmacists. Finally, some suggestions for further research on this under-studied issue are suggested.

Self-reported overdose among injecting drug users in London: extent and nature of the problem.

AIMS: To estimate the extent and nature of overdose and factors associated with overdose among injecting drug users in London. DESIGN: Three hundred and twelve current injecting drug users were recruited and interviewed in community settings by a team of "privileged access interviewers". MEASUREMENTS: A structured questionnaire was used that covered the following areas: demographic characteristics, drug use, injecting behaviour, sharing practices, severity of drug dependence, experience of overdose, injecting-related health problems and treatment history. FINDINGS: The results showed that experience of overdose was common (38%). A majority (54%) had witnessed someone else overdose. Overdosing was not a solitary experience; over 80% of subjects who had overdosed had done so in the presence of someone else, but only 27% reported ambulances having been called. Factors found to be associated with overdose were: age at which injecting began; gender (women being more likely to experience overdose); use of alcohol; and polydrug injection. The overall rate of overdosing was one per 6 years of injecting; however, once an individual had an overdose the chance of having another increased. The risk of experiencing a first overdose fell with years of injecting. CONCLUSIONS: Harm-reduction interventions with drug injectors should educate users on the risk factors associated with overdose and actions that should be taken when someone has overdosed. Interventions designed to reduce the risk of overdose may be more effective if they are differentially targeted on drug injectors who have already experienced an overdose.

Functional localization of a melanoma tumor suppressor gene to a small (< or = 2 Mb) region on 11q23.

We have previously demonstrated the existence of a melanoma tumor suppressor gene(s) on the long arm of chromosome 11 through suppression of tumorigenicity assays. Although loss of heterozygosity studies also support this finding, only a large critical region (44 cM) has been identified to date on 11q22-25. To further localize a tumor suppressor gene(s) within this region, we have now generated and characterized nine melanoma microcell hybrids, each retaining an introduced fragment of 11q. Of the nine hybrids, four were suppressed for tumor formation in nude mice, while five formed tumors at the same rate as the parental melanoma cell line (UACC 903). Molecular analysis of the hybrids with 118 microsatellite markers narrowed the location of a putative suppressor gene to a small (< or =2 Mb) candidate region on 11q23 between the markers D11S1786 and D11S2077 and within the larger region frequently deleted in melanoma tumors and cell lines. While multiple tumor suppressor genes are likely to reside on 11q22-25, the presence of this region in all four suppressed hybrids supports the simplest model that a single locus is responsible for the suppressed phenotype observed in UACC 903.