Photoassociation of long-range nD Rydberg molecules.

We observe long-range homonuclear diatomic nD Rydberg molecules photoassociated out of an ultracold gas of Rb87 atoms for 34≤n≤40. The measured ground-state binding energies of Rb87(nD+5S1/2) molecular states are larger than those of their Rb87(nS+5S1/2) counterparts, which shows the dependence of the molecular bond on the angular momentum of the Rydberg atom. We exhibit the transition of Rb87(nD+5S1/2) molecules from a molecular-binding-dominant regime at low n to a fine-structure-dominant regime at high n [akin to Hund's cases (a) and (c), respectively]. In the analysis, the fine structure of the nD Rydberg atom and the hyperfine structure of the 5S1/2 atom are included.

The evidence for the use of recombinant factor VIIa in massive bleeding: development of a transfusion policy framework.

A review of the recent randomized control trial evidence of the use of recombinant factor VIIa (rFVIIa) in massive bleeding. rFVIIa is a recombinant genetically engineered clotting factor that has been used for the management of haemophilia patients with inhibitors. There has been increasing use in patients with massive bleeding, even when there is no underlying coagulation disorder present. In November 2006, the Canadian National Advisory Committee on Blood and Blood Products engaged in a consultation and review process with several leading Canadian experts to review and discuss the current evidence up to November 2006. There is little evidence to support the routine use of rFVIIa in massive bleeding on review of 13 randomized controlled trials. rFVIIa should only be considered as part of a transfusion policy framework for massive bleeding after all other transfusion and supportive measures are considered. An example of a policy framework is presented.

Serological biomarker screening and host factor analysis elucidating immune response heterogeneity in active pulmonary tuberculosis.

While mortality and morbidity from pulmonary tuberculosis (PTB) have improved, diagnosis of this infectious disease remains suboptimal without a point-of-care test. Antibody/ antigen-based serodiagnostics is the most amenable for point-of-care translation but hampered by a lack of validated biomarkers and a heterogeneous patient antibody response. Using a case-control design, we assessed serodiagnostic potential of immunoglobulins G, A, and dimeric IgA responses against 18 antigenic preparations, followed by antibody-subclass responses against antigen 60 (A60), and four markers of host innate immunity by enzymelinked immunoassay using sera samples (n=110) collected from April to October 2007 in VietNam from human immunodeficiency-negative patients with provisional diagnosis of PTB. We further analyzed host variables to investigate factors driving biomarker heterogeneity observed in patients. Among active pulmonary tuberculosis patients, low correlation was observed between anti-A60 antibody-classes, and between anti-A60 immunoglobulin G subclasses, but anti-A60 immunoglobulin A subclasses were significantly correlated. The best diagnostic combination of anti-A60 immunoglobulin G/A and a C-reactive protein "ruleout" remains insufficient at 82%/92% sensitivity/specificity (95%CI: 72-92%/82-98%). Heterogeneity of anti-A60 immunoglobulins G2, G3, M, as well as C-reactive protein and serum amyloid A levels observed in this study population appeared to be significantly associated with history of previous tuberculosis, hemoptysis, age, vaccination, night sweats, smoking, chest pain, fever, alcohol, and solid culture count. Further research on tuberculosis serological biomarkers may require consideration of host factors and new approaches using multiple biomarkers.

Participation as a leader in immersion weight loss treatment: a 1-year follow-up study.

Non-overweight individuals may follow aggressive weight management approaches alongside overweight/obese friends or family members; thus, research has begun to evaluate subsequent effects among non-overweight populations. A prior study evaluated the short-term effects of an immersion weight loss programme on healthy young adult staff leaders. Results indicated that participation seemed to benefit, not harm, the young adults. The current investigation examined 1-year eating disorder and weight trajectories in this sample. The total sample (N = 244) consisted of staff leaders (44.3%) and demographically similar comparison participants who completed eating disorder and weight assessments across four time points: baseline, end of summer, 6-week follow-up and 1-year follow-up. Forty-seven per cent of the original sample responded to all time points (staff leaders n = 60; comparison n = 55). Over the course of 1 year, risk trajectories did not differ between groups. Staff leaders did not report significant changes in body mass index, suggesting that they maintained healthy weight over the course of 1 year. Participation as an immersion weight loss programme leader appeared to be protective against weight gain, without increasing eating disorder risk, for healthy young adults. This provides further support for using weight management interventions across a wide range of individuals.

Dietary restraint: what's the harm? A review of the relationship between dietary restraint, weight trajectory and the development of eating pathology.

Dietary restraint has historically been implicated as a risk factor for the development of eating pathology. Despite existing findings, recent research suggests that many individuals are capable of practicing dietary restraint without negative effects. In order to successfully incorporate the positive aspects of dietary restraint into interventions for healthy weight management, a nuanced examination of the relationship between dietary restraint and resulting eating patterns is necessary. Accordingly, the current review seeks to clarify the existing literature with regard to dietary restraint. First, this review examines the construct of dietary restraint and differentiates dietary restraint from related constructs, such as weight loss dieting. Second, it identifies situations in which dietary restraint has been linked with positive outcomes, such as healthy weight management and prevention of eating pathology. Altogether, it appears that dietary restraint can prove a beneficial strategy for those attempting to control their weight, as it does not relate to increased levels of eating pathology when practiced as part of a well-validated weight management programme.

Participation as a leader in immersion weight loss treatment may benefit, not harm, young adult staff members.

Despite the success of weight-management programmes, some researchers caution that participation in an aggressive approach to weight management could promote the development of eating pathology. The current study evaluated the risks and benefits for young adults of serving as staff members in an immersion treatment of adolescent obesity over the course of a summer. Participants included weight loss staff members (n = 108) along with a comparison group of young adults with similar demographic characteristics (n = 136). Participants completed assessments of eating disorder and obesity risk at three time points: the beginning of the summer, the end of the summer and a 6-week follow-up. Weight loss leadership participants who were initially overweight lost weight over the course of the summer, but those at healthy weights maintained their weight. Comparison participants also maintained their weight during the summer. Weight loss staff members also increased dietary restraint over the summer, and increases in dietary restraint appeared to facilitate appropriate weight reduction. Participation as a leader in an immersion weight loss programme seemed to benefit, not harm, young adults; this suggests potential advantages for using weight controlling interventions in a wide range of individuals, including as an obesity prevention strategy.

Public health implications of molecular point-of-care testing for chlamydia and gonorrhoea in remote primary care services in Australia: a qualitative study.

OBJECTIVES: With accurate molecular tests now available for diagnosis of chlamydia and gonorrhoea (Chlamydia trachomatis (CT)/Neisseria gonorrhoeae (NG)) at the point-of-care (POC), we aimed to explore the public health implications (benefits and barriers) of their integration into remote primary care in Australia. METHODS: Qualitative interviews were conducted with a purposively selected group of 18 key informants reflecting sexual health, primary care, remote Aboriginal health and laboratory expertise. RESULTS: Participants believed that POC testing may decrease community prevalence of sexually transmitted infections (STIs), and associated morbidity by reducing the time to treatment and infectious period and expediting partner notification. Also, POC testing could improve acceptability of STI testing, increase testing coverage and result in more targeted prescribing, thereby minimising the risk of antibiotic resistance. Conversely, some felt the immediacy of diagnosis could deter certain young people from being tested. Participants also noted that POC testing may reduce the completeness of communicable disease surveillance data given the current dependence on reporting from pathology laboratories. Others expressed concern about the need to maintain and improve the flow of NG antibiotic sensitivity data, already compromised by the shift to nucleic acid-based testing. This is particularly relevant to remote areas where culture viability is problematic. CONCLUSIONS: Results indicate a high level of support from clinicians and public health practitioners for wider access to CT/NG POC tests citing potential benefits, including earlier, more accurate treatment decisions and reductions in ongoing transmission. However, the data also highlight the need for new systems to avoid adverse impact on disease surveillance. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registry: ACTRN12613000808741.

Short- and long-term changes in serum leptin dieting obese women: effects of caloric restriction and weight loss.

This study examined the effects of caloric restriction and weight loss on serum leptin concentrations in 49 obese women who participated in a 40-week weight loss program. During the first 12 weeks, half the subjects were provided a 1000 kcal/day low-calorie diet (LCD), compromised of portion-controlled foods, whereas the other half were prescribed a 1200 kcal/day balanced deficit diet (BDD) consisting of self-selected table foods. Thereafter, subjects in both conditions were instructed to consume approximately 1200-1800 kcal/day of self-selected foods, depending on their desired weight change. During the first 6 weeks, weight and serum leptin fell significantly more (P < 0.05) in women in the LCD condition than in the BDD condition. In the former group, the 55% reduction in baseline leptin was 10 times greater than the relative reduction in body weight. Stepwise multiple regression analysis revealed that degree of caloric restriction, but not weight loss, contribution significantly to the variance in the change in leptin at week 6. By contrast, long-term changes in leptin, when subjects had increased their calorie intake, were more strongly related to changes in weight and fat. At week 40, for example, weight loss account for 47% of the variance in the change in leptin. Serum leptin and body fat remained highly correlated after weight loss (r = 0.79, P < 0.001), as before (r = 0.66, P < 0.001). After treatment, however, we observed a greater-than-expected reduction in serum leptin concentrations, as expressed per kilogram of body fat. The significance of this finding remains to be determined.

Changes in resting energy expenditure after weight loss in obese African American and white women.

BACKGROUND: Previous studies showed that resting energy expenditure (REE) is lower in obese African American women than in obese white women. It is unknown, however, whether there are racial differences in how REE responds to weight loss and energy restriction. OBJECTIVE: We assessed REE, body composition, and respiratory quotient before and after weight loss in obese black and white women. DESIGN: We measured REE by indirect calorimetry and body composition by densitometry before and after 20-24 wk of treatment with a 3870-4289-kJ/d diet. Subjects were 109 obese females (24 black, 85 white) with a mean (+/-SD) body mass index (in kg/m2) of 36.3+/-5.0, weight of 95.7+/-12.6 kg, and age of 42.3+/-8.1 y. RESULTS: Before treatment, REE, adjusted for body composition, was significantly lower in black than in white subjects (P = 0.001). Black subjects lost significantly less weight during treatment than did white subjects (13.4+/-5.9 kg or 14.2+/-5.7% compared with 16.4+/-5.6 kg or 17.0+/-5.7%, respectively; P = 0.04). Analyses that controlled for initial REE and changes in fat mass and fat-free mass showed that blacks had significantly greater decreases in REE after treatment than did whites (9.9+/-7.3% compared with 6.3+/-7.4%; P = 0.02). CONCLUSION: This study suggests that weight loss results in greater reductions in REE in obese black women than in obese white women. These data underscore the need to consider both biological and behavioral factors when setting expectations and assessing outcomes for obesity treatment in African American women.

Prediction of intravenous theophylline dosage based on a single, nonsteady-state concentration: a clinical study of childhood status asthmaticus.

A pharmacokinetic model was applied to achieve therapeutic serum theophylline concentrations rapidly in 25 children with status asthmaticus. A sustained release theophylline preparation had been taken within 36 hours by 12 children; within 14 hours, seven had taken an immediate release preparation; for six children, no theophylline was taken before hospital admission. Single serum theophylline concentrations were determined at nonsteady-state conditions within 13.5 hours of admission (median 6.75 hours). An iterative program was applied to predict the steady-state theophylline concentration as well as necessary adjustments in dosage. Measured steady-state concentrations were then compared with the predicted values. The median measured steady-state concentration was 15 mg/L, and the median predicted steady-state level was 13 mg/L. The least squares regression line was: Measured = 0.738 predicted + 4.77; r = .721, P less than .01. No patient experienced symptoms of toxicity. This technique affords the possibility of accurate prediction of steady-state theophylline concentrations and dosing requirements with a minimum number of serum concentration determinations in children with status asthmaticus.

Characterization of hepatitis A virus capsid proteins with antisera raised to recombinant antigens.

The capsid proteins of hepatitis A virus (HAV) were expressed as fusion proteins of beta-galactosidase in E. coli using the expression vector lambda gt11. Four fusion proteins were stably expressed and used to immunize rabbits to obtain mono-specific antisera. The antisera were unable to neutralize viral infectivity or react with HAV by radioimmunoassay. Three of the antisera were able to recognize HAV antigens in infected BS-C-1 cells by immunofluorescence and denatured capsid proteins by immunoblot analysis. The antisera were used to investigate the migration of the capsid proteins in gels by immunoblot analysis using standard SDS-PAGE conditions and in gels containing urea. The migration of VP1 and VP3 correlated with their molecular weights predicted from the nucleotide sequence and was consistent in either the presence or absence of urea. However, VP2 migrated with an apparent molecular weight significantly higher than the predicted value and, in gels containing urea, migrated as a doublet. It is proposed that the upper band of this doublet represents VP0, the proteolytic precursor of VP2 and VP4. The relative molecular mass (Mr) of VP4 was estimated to be less than 1 kDa, which is substantially lower than the 2.5 kDa predicted from the nucleotide sequence.

Rapid and efficient purification of hepatitis A virus from cell culture.

Hepatitis A virus (HAV) characteristically remains strongly cell-associated when grown in culture, with only small yields in the culture supernatant. Cell factories (6000 cm2) of BS-C-1 cells infected with the cytopathic HM175A.Z strain of HAV for 3, 4 or 7 days were harvested using trypsin to disperse the infected cell monolayer, and cells were collected by low speed centrifugation. More than 70% of the yield of virus and viral antigen can thus be obtained in the packed cell pellet. Packed cell pellets were resuspended in 5 volumes of isotonic buffer and cell membranes lysed by the addition of a non-ionic detergent. After removal of nuclei by centrifugation, ionic detergent was added to the clarified cytoplasmic extract. Under these conditions, HAV particles (virions and empty capsids) are the only particulate material remaining in the sample, and were recovered in a single ultracentrifugation step through discontinuous sucrose/glycerol density gradients. In one day, this method yields viral antigen with minimal cellular contaminants, in a concentrated volume suitable for subsequent biochemical, vaccine or diagnostic uses. The yield of viral antigen over numerous batches varied from 200 to 1600 vaccine-equivalent doses per cell factory, with a titre of up to 1 x 10(10) infectious particles per ml.

High level expression of the capsid protein of hepatitis E virus in diverse eukaryotic cells using the Semliki Forest virus replicon.

The capsid protein of hepatitis E virus (HEV) is encoded by open reading frame 2 (ORF 2) and exhibits variable processing when expressed in insect and COS cells, but nothing is known of its processing in cells relevant to its replication. The full-length ORF 2 protein was expressed at high levels in mammalian cells by insertion of ORF 2 in the Semliki Forest virus (SFV) replicon to generate rSFV/HEV ORF 2K. Expression of the capsid protein was detected readily by metabolic labelling and indirect immunofluorescence in BHK-21 cells transfected with RNA transcripts derived from rSFV/HEV ORF 2K. ORF 2 protein was also expressed at high levels in cells of diverse origin, including liver-derived cell lines Huh7 and HepG2, following infection with recombinant virus derived from cotransfection of BHK-21 cells with the rSFV/HEV ORF 2K and helper SFV replicon RNAs. The addition of hypertonic KCl during metabolic labelling reduced the level of host cell protein synthesis and enhanced the detection of intermediates in ORF 2 protein processing. The wide host range and high level expression directed by SFV replicon particles has particular utility in the analysis of cell-specific factors in the protein processing and assembly of non-cultivable viruses such as HEV.

ELISA for IgG-class antibody to hepatitis E virus based on a highly conserved, conformational epitope expressed in Escherichia coli.

In assays based on most recombinant hepatitis E virus (HEV) antigens, the IgG antibody responses to HEV are observed commonly to wane or disappear after the acute phase of infection. Such IgG assays have therefore been used for the diagnosis of acute HEV infection, but they have limited usefulness in seroepidemiological studies. Using western immunoblotting, it was shown previously that the open reading frame (ORF) 2.1 antigen, representing the carboxy-terminal 267 amino acids (aa) of the capsid protein, exposes a conformational epitope which allows optimal detection of convalescent antibody compared to other proteins expressed in Escherichia coli. This conformational epitope is shown to be highly conserved between divergent human HEV isolates, and the development of a sensitive and highly specific enzyme immunoassay (ELISA) based on this recombinant antigen is described. The ORF2.1 ELISA allows the detection and quantitation of both acute- and convalescent phase HEV-specific IgG, and will help to define better the antibody responses to the virus and the prevalence of HEV infection worldwide.

The new world of managed care: creating organized delivery systems.

In response to managed care pressures and imminent legislative reforms, provider organizations across the United States are coming together to form organized or integrated delivery systems. This paper describes various approaches to developing such systems and, drawing on ongoing research, examines what is known about the performance of such systems, the barriers they face, and the key factors likely to be associated with their success. The paper also addresses important policy questions related to the extent to which organized delivery systems should be actively encouraged by health reform legislation and how such systems should be held accountable.

The efficacy of cognitive-behavioral therapy on the core symptoms of bulimia nervosa.

Cognitive behavioral therapy (CBT) is widely regarded as the treatment of choice for bulimia nervosa (BN), with previous reviews of the CBT outcome literature claiming an approximate 40%-50% recovery rate. Most of these reviews have focused on reductions of binge eating and purging; however, the cognitive model of BN that underlies the CBT approach identifies three additional symptoms as central to the disorder: restrictive eating, concerns with shape and weight, and self-esteem. The purpose of this review was to determine the effect of CBT on the five core symptoms of BN, particularly those neglected in previous reviews. This review found that while most studies provided outcome data on binge eating, purgative behavior, and concern with shape and weight, fewer studies provided data on restraint and self-esteem. While generally favorable, evidence for the efficacy of CBT on the core symptoms of BN was mixed, depending on the outcome measures used. Shortcomings in the literature are identified and suggestions to correct these shortcomings are provided.

Exercise and the maintenance of weight loss: 1-year follow-up of a controlled clinical trial.

This study reports results 1 year after treatment for 77 obese women who had been treated for 48 weeks by diet combined with supervised (a) aerobic exercise, (b) strength training, (c) aerobic plus strength training combined, or (d) no exercise. Mean (+/- SD) end-of-treatment weight losses for the 4 conditions ranged from 13.5 +/- 9.1 kg to 17.3 +/- 10.3 kg, but there were no statistically significant differences among groups. Participants in all 4 conditions regained approximately 35% to 55% of their weight loss in the year after treatment; again, there were no significant differences among groups. Participants, however, who reported exercising regularly in the 4 months preceding the follow-up assessment regained significantly less weight than did nonexercisers.

Serological evidence for swine hepatitis E virus infection in Australian pig herds.

Hepatitis E virus (HEV) is an enterically transmitted human pathogen, with some similarities to caliciviruses. A variant of HEV was recently identified in pigs in the USA, infecting almost 100% of animals in commercial herds. Phylogenetic analysis suggests that this is a true 'swine HEV' distinct from the human virus, but the swine virus may also infect man. Using an in-house ELISA based on a highly conserved, recombinant HEV protein, we have examined collections of sera from Australian pigs for evidence of HEV infection in local pig herds. Sera from one research herd (n = 32) were uniformly non-reactive, and this was used to establish an assay cut-off (= mean + 3 SD of reference pig serum reactivities). Screening of sera from other herds demonstrates that swine HEV is present in Australia, with reactivity observed in 30% (12/40) of random samples from two piggeries, 92-95% of pigs by the age of 16 weeks in two other piggeries (n = 45), and 17% (15/59) of wild-caught pigs. Further studies are required to examine whether HEV causes disease in pigs and to determine the risk of swine HEV transmission to man.

The use of a mental status examination in a chemical dependence treatment program.

Current chemical dependence treatment programs place significant cognitive demands on patients early in abstinence. Unfortunately, many chemically dependent persons have significant cognitive deficits in the acute and post-acute stages of withdrawal. Constraints on resources often make thorough evaluation of cognitive status impractical. We examined the utility of a brief structured mental status examination, the Cognitive Capacity Screening Examination (CCSE), to identify cognitive deficits within the first week of admission to an inpatient chemical dependence treatment program. Although both age and educational level influenced CCSE total score to a statistically significant degree, the magnitude of their influence was of doubtful clinical importance. Findings suggest that the CCSE total score is not sufficiently sensitive to detect the deficits seen in chemically dependent individuals. However, a more detailed item analysis can provide useful information to the clinician. Normative data and recommendations for use of the CCSE with chemically dependent populations are provided.

Annulate lamellae and lytic HAV infection in vitro.

The aim of this study was to examine the relationship between viral infection and annulate lamellae (AL) production by using quantitative and qualitative electron microscopy to document the size and numbers of AL in BS-C-1 cells infected with a lytic strain of hepatitis A virus (HAV). The progress of the HAV infection was found to occur in two phases. In phase 1, cell proliferation and cell death were roughly the same as that of the mock infected control, but there was an increase with time in the amount of hepatitis A antigen in the infected cells. In phase 2 cell division was minimal and cell death became manifest. AL were detected in both infected and control cells. Quantitative analysis indicated that the average number of AL was greater in infected cells compared to that in control cells in phase 1; in infected cells there were greater numbers of AL in phase 1 than in phase 2; the average number of membraneous leaves/AL was greater in infected cells than in control cells. Quantitative analysis also indicated that AL were very rare, with only about three AL per entire control cell and eight AL per entire infected cell. The study clearly establishes that viral infection can stimulate AL production. The data suggest stimulation of AL production in the virus infected cells was linked to the synthesis of viral antigen. Ultrastructural observations indicated that AL could be derived from either the rough endoplasmic reticulum or the nuclear membrane.