Social and economic costs of gambling problems and related harm among UK military veterans.

INTRODUCTION: Military veterans are at heightened risk of problem gambling. Little is known about the costs of problem gambling and related harm among United Kingdom (UK) Armed Forces (AF) veterans. We investigated the social and economic costs of gambling among a large sample of veterans through differences in healthcare and social service resource use compared with age-matched and gender-matched non-veterans from the UK AF Veterans' Health and Gambling Study. METHODS: An online survey measured sociodemographic characteristics, gambling experience and problem severity, mental health and healthcare resource utilisation. Healthcare provider, personal social service and societal costs were estimated as total adjusted mean costs and utility, with cost-consequence analysis of a single timepoint. RESULTS: Veterans in our sample had higher healthcare, social service and societal costs and lower utility. Veterans had greater contacts with the criminal justice system, received more social service benefits, had more lost work hours and greater accrued debt. A cost difference of £590 (95% CI -£1016 to -£163) was evident between veterans with scores indicating problem gambling and those reporting no problems. Costs varied by problem gambling status. CONCLUSIONS: Our sample of UK AF veterans has higher healthcare, social service and societal costs than non-veterans. Veterans experiencing problem gambling are more costly but have no reduction in quality of life.

Assessment of the genetic and economic impact of performance recording and genotyping in Australian commercial sheep operations.

With the new opportunities from DNA technology, multitier breeding schemes have the potential to become more effective and more integrated. Integrated breeding schemes can also be better adapted to account for potential genotype by environment interactions (G × E) between tiers. In this case, phenotypic and genotype information from lower tiers becomes more valuable as it involves measurement of traits that directly represent the breeding objective. The objective of this study was to compare scenarios that represented different selection strategies and their economic effectiveness in fine-wool commercial sheep operations that exploit multitier breeding structures. Genomic selection (GS) applied in the multiplier and the commercial tier presented the largest additional revenue among all scenarios, as it resulted in the largest amount of genetic progress. The largest benefits from GS were outweighed by the genotyping costs, which made DNA parentage the most feasible strategy for the multiplier tier, resulting in the highest cumulative net present value (CNPV). The benefits of phenotypes and genotype information from the commercial environment were larger in the presence of G × E between the nucleus and the commercial tier. The CNPV was larger with a 50% reduction in genotyping costs, which increased the returns of GS scenarios by 2.7-fold on average. Higher selection intensity when selecting multiplier rams also resulted in larger benefits. In this case, returns for the breeding scheme were 3.5-fold higher when 33% of multiplier males were selected based on commercial information, compared to scenarios selecting 50% of the available multiplier rams. The benefits of collecting commercial phenotypes and genotypes were long term, which means that return on investment often took more than 10 years to be achieved, and were largely dependent on two-stage selection to reduce cost while maintaining selection efficiency and on the cost of a genotype test.

Non-invasive monitoring of male and female numbat (Myrmecobius fasciatus: Myrmecobiidae) reproductive activity.

The reproductive endocrinology of the highly endangered numbat (Myrmecobius fasciatus) is described for the first time. Patterns of faecal steroid secretion (progesterone [PM], oestradiol-17ß [E2] and testosterone [TM] metabolites) were examined within a captive numbat population over 1 year and revealed a highly synchronized seasonal pattern of reproduction. TM secretion increased progressively from September to November, peaked in December and then decreased in February. All females displayed luteal phases (1-3), between late-November to late-March, in association with pregnant (Pr, n=4), non-productive mated oestrous cycles (NMEC, n=8) and non-mated oestrous cycles (NEC, n=6). The mean oestrous cycle length was 30.2 ± 1.1 d (n=11) and was comprised of a mean follicular (n=11) and luteal (n=18) phase length of 16.2 ± 1.6 d and 14.0 ± 0.8 d, respectively. No variation in mean luteal phase length or PM concentration according to cycle type (Pr, NMEC, NEC) or cycle number (1st, 2nd or 3rd cycle) was detected. Longitudinal profiling of PM secretion confirmed that the female numbat is seasonally polyoestrous and that the luteal phase occurs spontaneously. Changes in the secretion of E2 provided little instructive information on oestrous cycle activity. Mating success was 31%, with age and subject having no effect on mating success. Timing of introduction, of male to female, appeared to impact mating success, with paired animals introduced for a shorter time frame (≤14 d) prior to the first observed mating successfully producing young. Collectively, results of the present study confirm that PM and TM can be reliably used to index numbat reproductive activity.

Endogenous knockdown of survivin improves chemotherapeutic response in ALL models.

Although the cure rate of newly diagnosed acute lymphoblastic leukemia (ALL) has improved over the past four decades, the outcome for patients who relapse remains poor. New therapies are needed for these patients. Our previous global gene expression analysis in a series of paired diagnosis-relapse pediatric patient samples revealed that the antiapoptotic gene survivin was consistently upregulated upon disease relapse. In this study, we demonstrate a link between survivin expression and drug resistance and test the efficacy of a novel antisense agent in promoting apoptosis when combined with chemotherapy. Gene-silencing experiments targeting survivin mRNA using either short-hairpin RNA (shRNA) or a locked antisense oligonucleotide (LNA-ON) specifically reduced gene expression and induced apoptosis in leukemia cell lines. When used in combination with chemotherapy, the survivin shRNA and LNA-ON potentiated the chemotherapeutic antileukemia effect. Moreover, in a mouse primary xenograft model of relapse ALL, the survivin LNA-ON decreased survivin expression in a subset of animals, and produced a statistically significant decrease in tumor progression. Taken together, these findings suggest that targeting endogenous levels of survivin mRNA by LNA-ON methods may augment the response to standard chemotherapy by sensitizing otherwise resistant tumor cells to chemotherapy.

Non-invasive methods of oestrus detection in captive southern hairy-nosed wombats (Lasiorhinus latifrons).

In order to develop a reliable method of oestrus detection in captive southern hairy-nosed (SHN) wombats, the reproductive behaviour of four groups of adult animals (1 male:2 female) was monitored using video surveillance and activity using movement-sensitive radio transmitters for a period of 12 months. During this time faecal samples were collected every 3 days and subsequently analysed for progesterone and oestradiol-17beta metabolites. In an attempt to induce and characterise oestrus-specific behaviour, each female was administered a subcutaneous injection of either 0.01 (n=2), 0.1 (n=4) or 0.2mg/kg (n=2) of oestradiol benzoate in one of two hormone trials. Remote video surveillance was an effective tool for detecting the reproductive behaviour of the captive SHN wombat. Courtship (n=426) and mating (n=46) was observed in five wombats and consisted of 13 distinctive behaviours in six consecutive phases: (1) investigation, (2) attraction, (3) chase, (4) restraint, (5) copulation and (6) recovery. Female sexual receptivity occurred at night and lasted for approximately only 13-h. Faecal progesterone metabolite analysis proved to be a reliable method for mapping oestrous cycle activity, but was not useful for the prediction of oestrus. Six out of the eight female wombats displayed periods of elevated progesterone secretion, corresponding to a mean (+/-SE) luteal phase of 20.9+/-1.1 days (n=23). Oestrous cycle length, defined as the interval between two successive luteal phases separated by a follicular phase was 31.8+/-1.1 days (n=12) and consisted of a follicular phase of 11.6+/-0.6 days (n=12). Changes in the secretion of faecal oestradiol-17beta metabolites provided little instructive information on oestrous cycle activity and were not associated with oestrus. Administration of oestradiol benzoate resulted in a spike of oestradiol-17beta metabolites in the faeces 3-4 days later, but was not dose dependent nor did it facilitate reproductive behaviour in either sex. Activity was not linked to key events in the oestrous cycle and appears not to be suitable as a method for detecting oestrus in the SHN wombat. We therefore recommend the use of 24-h video surveillance as the most reliable method for oestrus detection in captive SHN wombats.

Monitoring male southern hairy-nosed wombat (Lasiorhinus latifrons) reproductive function and seasonality in a captive population.

This study reports on the development and application of techniques used to assess the reproductive status of captive male southern hairy-nosed wombats (n=4) at Rockhampton Zoo. Initially, a GnRH agonist was used to establish a method for determining a reliable index of plasma and faecal testosterone secretion. Intra-muscular injection of buserelin (4 microg) resulted in an increase (P<0.05) in plasma and faecal testosterone concentration 90 min and 3 days after administration, respectively. Seasonal changes in faecal androgen, sperm production (spermatorrhoea) and testicular, prostatic and bulbourethral gland size were examined over a 18-month period, with prostate and bulbourethral gland cross-sectional areas being assessed by ultrasonography. Plasma testosterone secretion increased from early late winter and then decreased in spring (P<0.001); no seasonal variation (P=0.22) in faecal testosterone metabolite concentrations was apparent. Testicular volume showed no significant variation (P=0.29) over the sampling period. While there was no seasonal change (P=0.197, n=54) in prostate size, bulbourethral gland size increased in late-autumn, peaked in mid-winter and declined in early summer (P= or <0.001, n=55). Spermatozoa were found in the urine throughout the year. While, the captive population of SHN wombats at Rockhampton Zoo demonstrated significant changes in reproductive function, the extent of seasonality was less pronounced than that previously reported for wild populations in Southern Australia.

Body piercing: more than skin deep.

Young adult populations (18-25 years of age) throughout the world have latched onto the mainstream trend of body piercing. Best health care practices for these individuals involves the knowledge of proper procedural techniques, postsite care, common complications, and treatment modalities.

Changes in the ST-interval segment of the fetal electrocardiogram in relation to acid-base status at birth.

OBJECTIVE: To assess the occurrence of ST-interval segment changes of the fetal electrocardiogram (ECG) and cardiotocographic (CTG) abnormalities preceding acidaemia at birth. DESIGN: Case-control study. SETTING: University hospital labour ward. SAMPLE: Newborns with severe cord artery metabolic acidaemia (pH < 7.00 and lactate > or = 10 mmol/l; n= 24), moderate metabolic acidaemia (pH 7.00-7.09 and lactate > or = 10; n= 48), acidaemia (pH 7.00-7.09; n= 52), pre-acidaemia (pH 7.10-7.19; n= 265), and controls (pH > or = 7.20; n= 117). METHODS: Monitoring traces were assessed blinded to outcome. MAIN OUTCOME MEASURES: CTG and ST changes. RESULTS: Any ST event occurred significantly more often among cases with severe (79%) and moderate (75%) metabolic acidaemia than among controls (50%). The difference was restricted to baseline T/QRS rises and to the second stage of labour, during which any event only occurred significantly more often among cases with severe metabolic acidaemia (62%) than among controls (38%). ST events coincided with abnormal CTG patterns in 67, 44, 40, and 28% of cases with severe and moderate metabolic acidaemia, acidaemia, and pre-acidaemia, respectively, and in 12% of controls. ST events with intermediary CTG were similarly frequent in the case groups (0-6%) as in the controls (4%). The ST guidelines stated intervention in 96, 62, 73, and 49% of case groups and 23% of controls. CONCLUSIONS: Only two of three cases with severe and less than half of cases with moderate metabolic acidaemia were preceded by ST events coinciding with CTG abnormalities. It is therefore important to intervene for long-lasting, rapidly deteriorating or marked (preterminal) CTG abnormalities, also in the absence of ST events.

Oral cancer at a Tasmanian tertiary referral clinic, the Royal Hobart Hospital 1996-2002.

BACKGROUND: The Holman Clinic at the Royal Hobart Hospital includes a multi-disciplinary head and neck clinic which functions as a tertiary referral centre for Southern Tasmania and involves Ear Nose and Throat surgeons, Oral and Maxillofacial Surgeons, Plastic and Reconstructive Surgeons, Radiation Oncologists and Medical Oncologists. METHODS: The aim of this study was to examine retrospectively the number, gender distribution, age, site of lesion, histology, mortality and treatment modalities of the oral cancers referred to the Holman clinic at the Royal Hobart Hospital. The medical histories and a database of the Holman clinic were used as the sources of data for this study. A total of 101 patients were treated for oral cancer in the Holman clinic at the Royal Hobart Hospital from 1996 to 2002. There were 64 males and 37 females. RESULTS: The distribution of anatomical sites of the oral cancers in this study was as follows: 36 oral tongue lesions, 17 floor of mouth, 13 lip, five retromolar trigone, five mandibular alveolus, six buccal mucosa, nine palatal and 10 minor and major salivary gland cancers. The most common site of oral cancer was the tongue (35.6 per cent), followed by the floor of mouth (16.8 per cent) and lip (12.9 per cent). CONCLUSIONS: The majority of oral cancers were squamous cell carcinoma, except for the salivary gland cancers. The incidence of squamous cell carcinoma was between 67 and 100 per cent, depending upon the site involved. The trends found in this study are similar to those previously documented over the past 20 years.

Canine eruption into grafted alveolar clefts: a retrospective study.

BACKGROUND: The contemporary treatment of cleft lip and palate involves a sequence of surgical procedures and orthodontic management. Alveolar bone grafting (ABG) is usually undertaken after orthodontic expansion of the maxillary segments between the ages of eight and 12 years. Two of the important goals of alveolar bone grafting are the provision of bony support for the eruption of the canine and the closure of residual oro-nasal fistulae. The purpose of this study was to retrospectively evaluate the root development and eruption of the canine following ABG. METHODS: Group 1: radiographic and clinical records of a sample of 19 cleft patients who underwent alveolar bone grafting procedures, performed between 1996 and 1999 were reviewed. Group 2: a random sample of 15 cleft patients attending for routine dental review were clinically examined. The age of patient, degree of root development and eruption status of the canine, and presence of oronasal fistulae pre and post alveolar bone grafting were evaluated. RESULTS: Most cleft canines had continued root development and descended in the alveolus towards eruption following ABG. Four canine teeth (8 per cent) were impacted and required surgical exposure and orthodontic treatment following failure of eruption. Closure of anterior oro-nasal fistulae at the time of grafting was maintained post-operatively. CONCLUSIONS: This study demonstrated that canine root development and eruption continued satisfactorily through grafted alveolar clefts in most cases and closure of anterior oro-nasal fistulae was achieved in all cases.

The microtensile strength of bonding resins.

BACKGROUND: The purpose of this study was to determine the effect of water on the tensile strength of three bonding resins (All Bond 2, Scotchbond Multi-Purpose Adhesive, Clearfil LB Bond) and a low viscosity resin composite (Protect Liner F) after 1, 7, 28, 84 and 168 days of storage. METHODS: Cylinders of bonding resin 2.4 +/- 0.2 mm diameter and 9.5 mm long were made and stored at 37 degrees C for 24 hours. The specimens were milled into dumb-bell shapes and stored in either air or water at 37 degrees C. Five specimens of each material were stressed in tension after the specified storage times at a crosshead speed of 1 mm/min in a testing jig attached to a universal testing machine. The mean tensile strengths of bonding resins were calculated and analysed statistically using one-way analysis of variance, lower standard deviation and student t-tests. RESULTS: Comparison of the air and water samples at all test periods showed the tensile strengths of specimens stored in water were significantly less than those stored in air (P < 0.001). CONCLUSION: The effect of water on the tensile strength of bonding resins indicated a slight decrease in strength of each material over the 168 day test period, whereas the air samples showed little change over the test period.

Mycobacterium bovis strain bacillus Calmette-Guérin-induced liver granulomas contain a diverse TCR repertoire, but a monoclonal T cell population is sufficient for protective granuloma formation.

Granuloma formation is a form of delayed-type hypersensitivity requiring CD4(+) T cells. Granulomas control the growth and dissemination of pathogens, preventing host inflammation from harming surrounding tissues. Using a murine model of Mycobacterium bovis strain bacillus Calmette-Guérin (BCG) infection we studied the extent of T cell heterogeneity present in liver granulomas. We demonstrate that the TCR repertoire of granuloma-infiltrating T cells is very diverse even at the single-granuloma level, suggesting that before granuloma closure, a large number of different T cells are recruited to the lesion. At the same time, the TCR repertoire is selected, because AND TCR transgenic T cells (Valpha11/Vbeta3 anti-pigeon cytochrome c) are preferentially excluded from granulomas of BCG-infected AND mice, and cells expressing secondary endemic Vbeta-chains are enriched among AND cells homing to granulomas. Next, we addressed whether TCR heterogeneity is required for effective granuloma formation. We infected 5CC7/recombinase-activating gene 2(-/-) mice with recombinant BCG that express pigeon cytochrome c peptide in a mycobacterial 19-kDa bacterial surface lipoprotein. A CD4(+) T cell with a single specificity in the absence of CD8(+) T cells is sufficient to form granulomas and adequately control bacteria. Our study shows that expanded monoclonal T cell populations can be protective in mycobacterial infection.

Mycobacterium bovis BCG-induced granuloma formation depends on gamma interferon and CD40 ligand but does not require CD28.

Progressive granuloma formation is a hallmark of chronic mycobacterial infection. Granulomas are localized, protective inflammatory reactions initiated by CD4+ T cells, which contribute to control of bacterial growth and blockade of bacterial dissemination. In order to understand the costimulatory requirements that allow CD4+ T cells to directly or indirectly induce granulomas, we studied granuloma formation after 6 weeks in Mycobacterium bovis BCG-infected CD28- and CD40 ligand (CD40L)-deficient mice and compared it to granuloma formation in infected wild-type inbred mice and infected cytokine-deficient mice. We characterized granulomas morphologically in liver sections, analyzed granuloma infiltrating cells by flow cytometry, and measured cytokine production by cultured granuloma cells. CD28-deficient mice have no defect at the local inflammatory site, inasmuch as they form protective granulomas and control bacterial growth. However, there are fewer activated T cells in the spleen compared to infected wild-type animals, and quantitative differences in the cellular composition of the granuloma are observed by flow cytometry. In CD40L-deficient mice, the granuloma phenotype is very similar to the phenotype in gamma interferon (IFN-gamma)-deficient mice. Both IFN-gamma-deficient and CD40L-deficient mice form granulomas which prevent bacterial dissemination, but control of bacterial growth is significantly impaired. The relative proportion of CD4+ T cells in granulomas from both CD28(-/-) and CD40L(-/-) mice is significantly decreased compared with wild-type animals. Both models demonstrate that the phenotype and activation stage of systemic T cells do not always correlate with the phenotype and activation stage of the localized granulomatous response.

T-Cell epitopes and human leukocyte antigen restriction elements of an immunodominant antigen of Blastomyces dermatitidis.

Humans infected with the dimorphic fungus Blastomyces dermatitidis develop strong T-lymphocyte responses to WI-1, an immunodominant antigen that has been shown to elicit protective immunity in mice. In the present study, the T-cell epitopes of WI-1 and human leukocyte antigen (HLA) restricting elements that display them were investigated. Peripheral blood mononuclear cells (PBMC) from 37 patients with a confirmed history of blastomycosis were tested for a response to WI-1 in primary proliferation assays; PBMC from 35 (95%) responded. Six patients whose PBMC proliferated strongly in response to WI-1 (defined as a stimulation index greater than 50) were tested further for responses to subcloned, recombinant fragments of the antigen. These patients responded chiefly to sequences within the N terminus and the 25-amino-acid tandem repeat. Cloned CD4(+) T cells from an infected individual were used to delineate more precisely the peptide epitopes in the fragments and HLA restricting elements that present them. A majority of the T-cell clones recognized an epitope spanning amino acids 149 to 172 within the N terminus, displayed by HLA-DR 15. A minority of the clones, which have been shown to perform a cytolytic function in vitro, recognized an epitope in the tandem repeat displayed by HLA-DPw4, an uncommon restricting element. Tandem repeat epitopes required display by the beta chain of DPw4 heterodimers. Thus, human T cells with different functions in vitro also recognize distinct regions of WI-1, raising the possibility that HLA restricting elements that present them could modulate immunity during blastomycosis by selection and display of WI-1 peptides.

TCR specificity in infection induced granulomas.

Granuloma formation is an essential host response to many intracellular pathogens and some particulate antigens. T lymphocytes, especially CD4+ T-cells, are required for the initial formation and ongoing maintenance of the inflammatory response. In the absence of CD4+ T-cells, most infections which normally provoke a granulomatous response are more widely disseminated or lethal since the protective lesions are either malformed or absent. The role of T-cell receptor mediated antigen specificity in infectious states is reviewed with a special emphasis upon recent work on S. mansoni induced granulomas.

African strains of Blastomyces dermatitidis that do not express surface adhesin WI-1.

African strains of Blastomyces dermatitidis differ from North American strains in their growth, morphology, and clinical disease phenotype. In addition, two serotypes, designated 1 and 2, have been described. We investigated African strains of B. dermatitidis for expression of the surface protein adhesin WI-1 and found that serotype 2 strains do not express it because they lack the coding sequence in their genome. The defect will make the strains useful for gene complementation and for testing the pathogenetic role of the WI-1 adhesin.

Transforming DNA integrates at multiple sites in the dimorphic fungal pathogen Blastomyces dermatitidis.

Blastomyces dermatitidis is a primary fungal pathogen of man and other mammals, but like many other human fungal pathogens, relatively little is known about the factors that account for its virulence and pathogenicity. We developed a transformation system to facilitate molecular genetic studies of putative virulence factors from B. dermatitidis. Transformation of the multinucleate yeasts was achieved by electroporation of DNAs containing a dominant selectable marker, hygromycin B (HygB) resistance. Southern analysis showed that transforming DNA invariably integrated ectopically into the chromosome. No evidence was found for extrachromosomal DNA. The HygB resistance could be expressed by either a 375-bp promoter fragment of the B. dermatitidis WI-1 gene encoding adhesin or an Aspergillus gpdA promoter placed 5' of the E. coli hph gene. Primer extension analysis showed that for plasmids containing the WI-1 promoter, transcription of the hph gene initiated within the 375-bp WI-1 promoter fragment. The combination of gene transfer and two promoters capable of independent transcription will allow us to restore or augment gene expression in appropriate strains and test an influence on virulence. Molecular genetic manipulation of B. dermatitidis represents a major advance in our ability to investigate the pathogenesis of blastomycosis and other similar fungal diseases.