Subtypes of Illicit Drug Users: A Latent Class Analysis of Data From an Australian Twin Sample

This article applies methods of latent class analysis (LCA) to data on lifetime illicit drug use in order to determine whether qualitatively distinct classes of illicit drug users can be identified. Self-report data on lifetime illicit drug use (cannabis, stimulants, hallucinogens, sedatives, inhalants, cocaine, opioids and solvents) collected from a sample of 6265 Australian twins (average age 30 years) were analyzed using LCA. Rates of childhood sexual and physical abuse, lifetime alcohol and tobacco dependence, symptoms of illicit drug abuse/dependence and psychiatric comorbidity were compared across classes using multinomial logistic regression. LCA identified a 5-class model: Class 1 (68.5%) had low risks of the use of all drugs except cannabis; Class 2 (17.8%) had moderate risks of the use of all drugs; Class 3 (6.6%) had high rates of cocaine, other stimulant and hallucinogen use but lower risks for the use of sedatives or opioids. Conversely, Class 4 (3.0%) had relatively low risks of cocaine, other stimulant or hallucinogen use but high rates of sedative and opioid use. Finally, Class 5 (4.2%) had uniformly high probabilities for the use of all drugs. Rates of psychiatric comorbidity were highest in the polydrug class although the sedative/opioid class had elevated rates of depression/suicidal behaviors and exposure to childhood abuse. Aggregation of population-level data may obscure important subgroup differences in patterns of illicit drug use and psychiatric comorbidity. Further exploration of a 'self-medicating' subgroup is needed.

Use of latent profile analysis to identify eating disorder phenotypes in an adult Australian twin cohort

Context: The relationships among the different eating disorders that exist in the community are poorly understood, especially for residual disorders in which bingeing or purging occurs in the absence of other behaviors. Objective: To examine a community sample for the number of mutually exclusive weight and eating profiles. Design: Data regarding lifetime eating disorder symptoms and weight range were submitted to a latent profile analysis. Profiles were compared regarding personality, current eating and weight, retrospectively reported life events, and lifetime depressive psychopathology. Setting: Longitudinal study among female twins from the Australian Twin Registry in whom eating was assessed by a telephone interview. Participants: A community sample of 1002 twins (individuals) who had participated in earlier waves of data collection. Main Outcome Measures: Number and clinical character of latent profiles. Results: The best fit was a 5-profile solution with women who were (1) of normal weight with few lifetime eating disorders (4.3%), (2) overweight (10.6% had a lifetime eating disorder), (3) underweight and generally had no eating disorders except for 5.3% who had restricting anorexia nervosa, (4) of low to normal weight (89.0% had a lifetime eating disorder), and (5) obese (37.0% had a lifetime eating disorder). Each profile contained more than 1 type of lifetime eating disorder except for the third profile. Women in the first and third profiles had the best functioning, with women in the fourth and fifth profiles having similarly poorer functioning. The women in the fourth group had a symptom profile distinctive from the other 4 groups in terms of severity; they were also more likely to have had lifetime major depression and suicidality. Conclusion: Lifetime weight ranges and the severity of eating disorder symptoms affected clustering more than the type of eating disorder symptom.

Expression of LAG-3 by tumor-infiltrating lymphocytes is coincident with the suppression of latent membrane antigen-specific CD8(+) T-cell function in Hodgkin lymphoma patients

In Hodgkin lymphoma (HL), the malignant Hodgkin Reed-Sternberg (HRS) cells constitute only 0.5% of 10% of the diseased tissue. The surrounding cellular infiltrate is enriched with T cells that are hypothesized to modulate antitumor immunity. We show that a marker of regulatory T cells, LAG-3, is strongly expressed on infiltrating lymphocytes present in proximity to HRS cells. Circulating regulatory T cells (CD4(+) CD25(hi) CD45 ROhi, CD4(+) CTLA4(hi), and CD4(+) LAG-3(hi)) were elevated in HL patients with active disease when compared with remission. Longitudinal profiling of EBV-specific CD8(+) T-cell responses in 94 HL patients revealed a selective loss of interferon-gamma expression by CD8(+) T cells specific for latent membrane proteins 1 and 2 (LMP1/2), irrespective of EBV tissue status. Intratumoral LAG-3 expression was associated with EBV tissue positivity, whereas FOXP3 was linked with neither LAG-3 nor EBV tissue status. The level of LAG-3 and FOXP3 expression on the tumor-infiltrating lymphocytes was coincident with impairment of LMP1/2-specific T-cell function. In vitro pre-exposure of peripheral blood mono-nuclear cells to HRS cell line supernatant significantly increased the expansion of regulatory T cells and suppressed LMP-specific T-cell responses. Deletion of CD4(+) LAG-3(+) T cells enhanced LMP-specific reactivity. These findings indicate a pivotal role for regulatory T cells and LAG-3 in the suppression of EBV-specific cell-mediated immunity in HL.

Discovering user access pattern based on probabilistic latent factor model

There has been an increased demand for characterizing user access patterns using web mining techniques since the informative knowledge extracted from web server log files can not only offer benefits for web site structure improvement but also for better understanding of user navigational behavior. In this paper, we present a web usage mining method, which utilize web user usage and page linkage information to capture user access pattern based on Probabilistic Latent Semantic Analysis (PLSA) model. A specific probabilistic model analysis algorithm, EM algorithm, is applied to the integrated usage data to infer the latent semantic factors as well as generate user session clusters for revealing user access patterns. Experiments have been conducted on real world data set to validate the effectiveness of the proposed approach. The results have shown that the presented method is capable of characterizing the latent semantic factors and generating user profile in terms of weighted page vectors, which may reflect the common access interest exhibited by users among same session cluster.

A web recommendation technique based on probabilistic latent semantic analysis

Web transaction data between Web visitors and Web functionalities usually convey user task-oriented behavior pattern. Mining such type of click-stream data will lead to capture usage pattern information. Nowadays Web usage mining technique has become one of most widely used methods for Web recommendation, which customizes Web content to user-preferred style. Traditional techniques of Web usage mining, such as Web user session or Web page clustering, association rule and frequent navigational path mining can only discover usage pattern explicitly. They, however, cannot reveal the underlying navigational activities and identify the latent relationships that are associated with the patterns among Web users as well as Web pages. In this work, we propose a Web recommendation framework incorporating Web usage mining technique based on Probabilistic Latent Semantic Analysis (PLSA) model. The main advantages of this method are, not only to discover usage-based access pattern, but also to reveal the underlying latent factor as well. With the discovered user access pattern, we then present user more interested content via collaborative recommendation. To validate the effectiveness of proposed approach, we conduct experiments on real world datasets and make comparisons with some existing traditional techniques. The preliminary experimental results demonstrate the usability of the proposed approach.

The effect of water fluoridation on the bone mineral density of young women [Saskatoon study]

Introduction: Osteogenic effects of therapeutic fluoride have been reported; however, the impact of exposure to low level water fluoridation on bone density is not clear. We investigated the effect of long-term exposure to fluoridated water from growth to young adulthood on bone mineral density (BMD). Methods: BMD was measured in 24 healthy women from Regina (fluoride 0.1 mg/L) and 33 from Saskatoon (fluoride 1.0 mg/L), with no differences between groups for height, weight, lifestyle or dietary factors. Results: Saskatoon women had significantly higher mean BMD at total anterior-posterior lumbar spine (APS) and estimated volumetric L3 (VLS), with no difference at total body (TB) or proximal femur (PF). Conclusion: Exposure to water fluoridation during the growing years may have a power impact on axial spine bone density in young women.

An investigation of the interrelationship between manipulative therapy-induced hypoalgesia and sympathoexcitation

Objective: To investigate a proposed model in which manipulative therapy produces a treatment-specific initial hypoalgesic and sympathoexcitatory effect by activating a descending pain inhibitory system. The a priori hypothesis tested was that manipulative therapy produces mechanical hypoalgesia and sympatho-excitation beyond that produced by placebo or control. Furthermore, these effects would be correlated, thus supporting the proposed model. Design: A randomized, double-blind, placebo-controlled, repeated-measures study of the initial effect of treatment. Setting: Clinical neurophysiology laboratory. Subjects: Twenty-four subjects (13 women and 11 men; mean age, 49 yr) with chronic lateral epicondylalgia (average duration, 6.2 months). Intervention: Cervical spine lateral glide oscillatory manipulation, placebo and control. Outcome Measures: Pressure pain threshold, thermal pain threshold, pain-free grip strength test, upper limb tension test 2b, skin conductance, pileous and glabrous skin temperature and blood flux. Results: Treatment produced hypoalgesic and sympathoexcitatory changes significantly grater than those of placebo and control (p < .03). Confirmatory factor-analysis modeling, which was performed on the pain-related measures and the indicators of sympathetic nervous system function, demonstrated a significant correlation (r = .82) between the latencies of manipulation-induced hypoalgesia and sympathoexcitation. The Lagrange Multiplier test and Wald test indicated that the two latent factors parsimoniously and appropriately represented their observed variables. Conclusions: Manual therapy produces a treatment-specific initial hypoalgesic and sympathoexcitatory effect beyond that of placebo or control. The strong correlation between hypoalgesic and sympathoexcitatory effects suggests that a central control mechanism might be activated by manipulative therapy.

Twice-weekly, directly observed treatment for HIV-infected and uninfected tuberculosis patients: cohort study in rural South Africa

Objective: To determine the effectiveness of twice-weekly directly observed therapy (DOT) for tuberculosis (TB) in HIV-infected and uninfected patients, irrespective of their previous treatment history. Also to determine the predictive value of 2-3 month smears on treatment outcome. Methods: Four hundred and sixteen new and 113 previously treated adults with culture positive pulmonary TB (58% HIV infected, 9% combined drug resistance) in Hlabisa, South Africa. Daily isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) given in hospital (median 17 days), followed by HRZE twice a week to 2 months and HR twice a week to 6 months in the community. Results: Outcomes at 6 months among the 416 new patients were: transferred out 2%; interrupted treatment 17%; completed treatment 3%; failure 2%; and cured 71%. Outcomes were similar among HIV-infected and uninfected patients except for death (6 versus 2%; P = 0.03). Cure was frequent among adherent HIV-infected (97%; 95% CI 94-99%) and uninfected (96%; 95% CI 92-99%) new patients. Outcomes were similar among previously treated and new patients, except for death (11 versus 4%; P = 0.01), and cure among adherent previously treated patients 97% (95% CI 92-99%) was high. Smear results at 2 months did not predict the final outcome. Conclusion: A twice-weekly rifampicin-containing drug regimen given under DOT cures most adherent patients irrespective of HIV status and previous treatment history. The 2 month smear may be safely omitted. Relapse rates need to be determined, and an improved system of keeping treatment interrupters on therapy is needed. Simplified TB treatment may aid implementation of the DOTS strategy in settings with high TB caseloads secondary to the HIV epidemic. (C) 1999 Lippincott Williams & Wilkins.

Emergence of multidrug-resistant tuberculosis in a community-based directly observed treatment programme in rural South Africa

OBJECTIVE: Although little studied in developing countries, multidrug-resistant tuberculosis (MDR-TB) is considered a major threat. We report the molecular epidemiology, clinical features and outcome of an emerging MDR-TB epidemic. METHODS: In 1996 all tuberculosis suspects in the rural Hlabisa district, South Africa, had sputum cultured, and drug susceptibility patterns of mycobacterial isolates were determined. Isolates with MDR-TB (resistant to both isoniazid and rifampicin) were DNA fingerprinted by restriction fragment length polymorphism (RFLP) using IS6110 and polymorphic guanine-cytosine-rich sequence-based (PGRS) probes. Patients with MDR-TB were traced to determine outcome. Data were compared with results from a survey of drug susceptibility done in 1994. RESULTS: The rate of MDR-TB among smear-positive patients increased six-fold from 0.36% (1/275) in 1994 to 2.3% (13/561) in 1996 (P = 0.04). A further eight smear-negative cases were identified in 1996 from culture, six of whom had not been diagnosed with tuberculosis. MDR disease was clinically suspected in only five of the 21 cases (24%). Prevalence of primary and acquired MDR-TB was 1.8% and 4.1%, respectively. Twelve MDR-TB cases (67%) were in five RFLP-defined clusters. Among 20 traced patients, 10 (50%) had died, five had active disease (25%) and five (25%) were apparently cured. CONCLUSIONS: The rate of MDR-TB has risen rapidly in Hlabisa, apparently due to both reactivation disease and recent transmission. Many patients were not diagnosed with tuberculosis and many were not suspected of drug-resistant disease, and outcome was poor.

Traditional healers as tuberculosis treatment supervisors: precedent and potential

SETTING: Hlabisa, South Africa. OBJECTIVE: To determine precedent and potential for traditional healers to act as tuberculosis (TB) treatment supervisors. METHODS: Literature review to describe precedent for the involvement of traditional healers in TB treatment supervision. Interviews with 100 TB patients to determine use of healers and their acceptability as supervisors. Interviews with 24 healers in the project sub-district to determine willingness to act as supervisors. RESULTS: Despite extensive literature on the interaction between traditional healers and conventional health services, including descriptions of traditional understandings of TB, no published work was identified that reported supervision of TB patients by traditional healers. Of 100 patients interviewed, only 10% had used a healer as the first health provider for their illness, but 40% had attended a healer at some time prior to diagnosis. Although only 4% believe healers can cure TB, 84% would consider choosing a healer as a treatment supervisor. Of the 24 healers, 15 (63%) distinguished between two types of diagnosis made among patients with. symptoms suggestive of TB: TB and idliso. Idliso is poisoning or bewitching, and is said to be best cured by healers, while TB is infectious and cannot be cured by healers. Most healers (88%) reported having referred patients with possible TB to hospital in the past; all were keen to negotiate collaboration with health services, and 92% were willing to act as treatment supervisors. CONCLUSIONS: While there is little reported precedent for traditional healers to interact formally with tuberculosis treatment services, the potential for collaboration seems to be high, at least in our setting.

A six-year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children: The University of Saskatchewan bone mineral accrual study

To investigate the influence of physical activity on bone mineral accrual during the adolescent years, we analyzed 6 years of data from 53 girls and 60 boys. Physical activity, dietary intakes, and anthropometry were measured every 6 months and dual-energy X-ray absorptiometry scans of the total body (TB), lumbar spine (LS), and proximal femur (Hologic 2000, array mode) were collected annually. Distance and velocity curves for height and bone mineral content (BMC) were fitted for each child at several skeletal sites using a cubic spline procedure, from which ages at peak height velocity (PHV) and peak BMC velocity (PBMCV) were identified. A mean age- and gender-specific standardized activity (Z) score was calculated for each subject based on multiple yearly activity assessments collected up until age of PHV. This score was used to identify active (top quartile), average (middle 2 quartiles), or inactive (bottom quartile) groups. Two-way analysis of covariance, with height and weight at PHV controlled for, demonstrated significant physical activity and gender main effects (but no interaction) for PBMCV, for BMC accrued for 2 years around peak velocity, and for BMC at 1 year post-PBMCV for the TB and femoral neck and for physical activity but not gender at the LS (all p < 0.05). Controlling for maturational and size differences between groups, we noted a 9% and 17% greater TB BMC for active boys and girls, respectively, over their inactive peers 1 year after the age of PBMCV. We also estimated that, on average, 26% of adult TB bone mineral was accrued during the 2 years around PBMCV.