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Objective: For 3 decades, studies have reported that the usual sequence of drug initiation is licit drugs, then cannabis, and then other illicit drugs. This article describes the prevalence of violations of this sequence, the predictors of violations, and the relationship between violations and the onset of alcohol or drug dependence.Method: The New Zealand Mental Health Survey is a nationally representative sample with 12,992 face-to-face interviews carried out in 2003-2004. The response rate was 73.3%. The World Health Organization Composite International Diagnostic Interview (CIDI 3.0) was used in the survey. Reports of the age at first use were obtained for alcohol and drugs but not for smoking.Results: Violations of the usual sequence of drug initiation were uncommon in the population (2.6%). Use of other illicit drugs before cannabis was the main violation, found in 2.3% of alcohol users, 3.0% of cannabis users, 8.6% of cocaine users, and 16.7% of those who had used other illicit drugs. Use of other illicit drugs before cannabis was more predominant in younger cohorts and those with more early-onset internalizing disorders. Violations had little association with the development of dependence in users when other important predictors such as age at onset of use and the number of illicit drugs used were taken into account. Internalizing disorders and early-onset bipolar disorder also predicted dependence.Conclusions: In New Zealand, violations of the gateway sequence are not common and they are not markers of progression to dependence. [ABSTRACT FROM AUTHOR]

The relationship between mental disorders and chronic physical conditions is well established, but the possibility of ethnic group differences in mental-physical associations has seldom been investigated. This study investigated ethnic differences in associations between four physical conditions (chronic pain, cardiovascular disease, diabetes, and respiratory disease) and 12-month mood and anxiety disorders. A nationally representative face-to-face household survey was carried out in New Zealand from 2003 to 2004 with 12,992 participants aged 16 and older, achieving a response rate of 73.3%. The current study is of the subsample of 7,435 participants who were assessed for chronic physical conditions (via a standard checklist), and compares Maori, Pacific and Other New Zealanders. DSM-IV mental disorders were measured with the Composite International Diagnostic Interview (CIDI 3.0). The ethnic groups differed significantly in prevalences of both physical and mental disorders, but almost no ethnic differences in mental-physical associations were found. Independent of ethnicity, associations were observed between chronic pain and mood and anxiety disorders, cardiovascular disease and anxiety disorders, respiratory disease and mood and anxiety disorders. Despite differences in mental and physical health status between ethnic groups in New Zealand, mental-physical disorder associations occur with considerable consistency across the groups. These results suggest that whatever factors are conducive to the development of a mental disorder from a physical disorder (or vice versa), they are either unaffected by the cultural differences manifest in these ethnic groups, or, any cultural factors operating serve to both increase and decrease comorbidity such that they cancel each other out. [ABSTRACT FROM AUTHOR]

Background: A better understanding of the factors associated with the size and/or progression of osteolytic lesions has been hampered by a lack of sensitivity of radiographic measurement techniques.Methods: We retrospectively analyzed quantitative computed tomography scans that had been made with use of a high-resolution multi-slice scanner with a metal artifact-suppression protocol. The scans had been made to determine the volume of osteolytic lesions around thirty-five cementless Harris-Galante acetabular components that had been in situ for at least ten years. Repeat scans of thirty hips allowed for the measurement of progression in the size of osteolytic lesions over a one-year period. Associations between the volume of osteolytic lesions, progression in the size of the lesions, polyethylene wear since the time of implantation, change in component position, and patient-related variables (age, gender, body mass index, activity level, walking limitations, joint pain, and function) were determined.Results: In sixteen of the thirty hips that had repeat computed tomography scans, the lesions progressed in size during the study period. The median size of the lesions in these sixteen hips was 10.3 cm(3) at the time of the initial scan, compared with 13.3 cm(3) at a median of fifteen months later (p = 0.001). Osteolytic lesions measuring >10 cm(3) in volume on the initial scan were 2.5 times (95% confidence interval 1.3 to 4.8 times) more likely to progress in size over one year than smaller lesions were. Patients with greater polyethylene wear rates, higher activity levels, no walking limitations, and larger prosthetic femoral head dimensions (26 or 28 mm) had significantly larger osteolytic lesions (p < 0.0001, p = 0.009, p = 0.006, and p = 0.028, respectively). Progression in the size of the osteolytic lesions over one year was significantly associated with larger initial osteolytic lesions (p = 0.002), greater polyethylene wear rates (p = 0.009), and larger (26 or 28-mm) prosthetic femoral head dimensions (p = 0.019).Conclusions: There is considerable variation in the rates of progression of the size of osteolytic lesions around stable acetabular components. Lesion size and the progression of lesion size are generally related to polyethylene wear rates, higher patient activity levels, and larger-diameter femoral heads. Osteolytic lesions measuring >10 cm(3) in volume are associated with a high rate of progression. [ABSTRACT FROM AUTHOR]

BACKGROUND: Evidence is needed for the best long-term diet for weight loss, and improvement in cardiac risk and disease in obese adults. METHODS: We systematically reviewed randomized controlled trials (RCTs) in any language. We searched 13 databases and handsearched journals. Trials lasted 1 year or more. One investigator extracted the data and a second checked data extraction. Trial quality was assessed. RESULTS: Low fat diets (LFDs) produced significant weight losses up to 36 months (-3.55 kg; 95% CI, -4.54 to -2.55 kg). Blood pressure, lipids and fasting plasma glucose improved with these diets after 12 months. Four studies found that LFDs may prevent type 2 diabetes and reduce antihypertensive medication for up to 3 years. A very low calorie diet (VLCD, < 4.2 MJ day(-1)) was associated with the most weight loss after 12 months (-13.40 kg; 95% CI, -18.43 to -8.37 kg) in one small study with beneficial effects on asthma. There was no evidence that low carbohydrate protein sparing modified fasts (PSMFs) were associated with greater long-term weight loss than low calorie diets (LCDs, 4.2-6.7 MJ day(-1)) or VLCDs. PSMFs were, however, associated with greater lowering of fasting plasma glucose and HbA1c than LCDs. CONCLUSIONS: Little evidence supports the use of diets other than LFDs for weight reduction. With the increasing prevalence of morbid obesity, long-term follow-up in RCTs is needed to evaluate the effect of LCDs, VLCDs and PSMFs more fully. [ABSTRACT FROM AUTHOR]

BACKGROUND: Evidence is needed for the effectiveness of interventions given with reducing diets for obese adults: drug therapy, exercise, or behaviour therapy. METHODS: We systematically reviewed randomized controlled trials in any language. We searched 13 databases and handsearched journals. Trials lasted 1 year or more. One investigator extracted data and a second checked data extraction. Trial quality was assessed. RESULTS: Adding orlistat to diet was associated with weight change for up to 24 months (-3.26 kg, 95% CI, -4.15 to -2.37 kg), and statistically significant beneficial changes were found for total and LDL cholesterol, blood pressure and glycaemic control. Adding sibutramine to diet was associated with a 12 month weight change of -4.18 kg (95% CI, -5.14 to -3.21 kg), and statistically significant beneficial effects on high density lipoprotein cholesterol (HDL) and triglycerides (TGs), but an increase in diastolic blood pressure. Adding exercise to diet, or to diet and behaviour therapy, was associated with improved weight loss for up to 36 months and improvements in HDL, TGs and blood pressure. Adding behaviour therapy to diet, or to diet and sibutramine together, was associated with improved weight loss for up to 18 months. Adding drugs, exercise or behaviour therapy to dietary advice was each associated with similar weight change. CONCLUSIONS: Adding orlistat, sibutramine, exercise, or behaviour modification to dietary advice can improve long-term weight loss. [ABSTRACT FROM AUTHOR]

Background: Surgeons traditionally undertake a prospective evaluation of patients undergoing total hip arthroplasty in order to determine outcomes. The validity of doctor-derived data is questionable because of the potential for interobserver error, reporting bias, and differences between the perceptions of doctors and patients. Also, the use of doctor-derived data necessitates the use of costly outpatient services. Consequently, there are likely to be benefits associated with the use of patient-derived clinical evaluation data. However, few studies have focused on whether data obtained from the patient and doctor differ.Methods: The agreement between patient and doctor responses on a sixteen-item total hip arthroplasty clinical evaluation questionnaire completed at more than 2900 clinical assessments was determined. Data from repeated assessments performed preoperatively and postoperatively enabled stratified analyses that were used to examine reasons for disagreement and factors influencing agreement. Agreement was measured with use of the kappa coefficient.Results: For twelve of the sixteen items, the patient responses had acceptable agreement with the doctor responses. Some important differences between patient-derived and doctor-derived data were found. If the patient had other joint or health problems, had a revision total hip arthroplasty, or reported mild or moderate pain, there was a greater chance of reduced agreement on the pain items. Younger patients demonstrated better agreement with doctors than older patients did.Conclusions: Patients' perceptions of symptoms and outcomes after total hip arthroplasty are relatively similar to those of their doctor. There is minimum risk of misinterpreting outcomes data by replacing doctor-completed questionnaires with patient-completed questionnaires in uncomplicated total hip arthroplasty cases. For patients with comorbid joint problems or other health problems, and for those reporting substantial pain, direct physician involvement in the evaluation of pain is recommended. The selective use of patient-completed questionnaires has the potential to substantially reduce the costs of outcomes evaluation programs by minimizing doctor input. Pending revision of some of the items, the use of this patient-completed questionnaire is advocated. [ABSTRACT FROM AUTHOR]

OBJECTIVE: to provide a profile of disorders and disabilities in the older population. DESIGN: the MRC CFAS drew population samples of people aged 64 years and over from Family Health Service Authority lists at five sites and asked participants about sociodemographic variables, physical and cognitive health and activities of daily living, We calculated the prevalence of co-morbidity from the number of different types of complaint or disability (physical, functional and cognitive), and calculated healthy life expectancies in each of these co-morbid states. SETTING: three urban (Newcastle, Nottingham and Oxford) and two rural sites (Cambridgeshire and Gwynedd). RESULTS: the prevalence of morbidity is low at the youngest ages, as is co-morbidity. Women have consistently greater morbidity than men. Morbidity increases sharply with age, with a more dramatic rise in women. Life expectancy without any morbidity is short at all ages over 64, with the number of years expected with two or more areas affected virtually constant up to 90 years. As a proportion of remaining life expectancy, the period of time spent with two or more areas affected rises by the age of 90 to 30% in men and 60% in women. CONCLUSIONS: preventive programmes for the older population should take into account the large differences between the young old, the middle old and the old old. Our study provides a baseline against which to compare future changes in health in older populations, as well as benchmark expectancies for the UK population. [ABSTRACT FROM AUTHOR]

Background: Chinese females are distinguished internationally as having relatively high lung cancer incidence rates despite a low prevalence of cigarette smoking. In Singapore, this population comprises several dialect groups which have origins in different regions in China, each with its own traditional cultural practices.Methods: An analysis of 4029 incident cases of the disease notified to the Singapore Cancer Registry for 1968-1992 was undertaken to provide some insight into important aetiologic factors among these women.Results: The age-standardized incidence rate of lung cancer rose from 17.3 per 100,000 woman-years in 1968-1972 to 23.0 in 1978-1982 before falling off in more recent years. Age-period-cohort analysis indicated significant period and birth cohort effects, with the risk being highest for women born around 1908. Between the major dialect groups, Cantonese women had a significantly high rate compared with Hokkiens (relative risk [RR] = 2.6, 95% CI: 2.4-2.8). Histologically, there appears to be an increase in the proportion of adenocarcinomas diagnosed over this period (25.8% in 1968-1972 to 51.3% in 1988-1992).Conclusion: Our results suggest that traditional practices which have decreased over the years, and are more prominent among Southern Chinese, may play a part in the aetiology of lung cancer locally. [ABSTRACT FROM AUTHOR]

Background: Until recently relatively little data have been available on the prevalence of dementia in the oldest age groups, and yet it is these age groups which are expanding fastest. It is therefore important to understand whether the prevalence of dementia rises inexorably with age ('age-dependent'), or, as some suggest, levels off or even declines in the very oldest age groups ('age-related'). Combined analysis of the many prevalence studies now available has led to modelled curves which do suggest a slowing of rise in prevalence at these great ages, and has been interpreted as meaning that dementia is age-related. This interpretation does not take into account the differential survival of individuals with cognitive impairment compared with normals of the same age.Method: Flexible prevalence-incidence-duration models were generated using a deterministic approach applied to published combined analyses of prevalence rates, population death rates and mortality odds ratios.Results: The variation in observed prevalence patterns with age is explained to a great extent by the mortality observed in the cognitively impaired. Simple examination of age patterns in prevalence does not answer the fundamental question surrounding the age-dependence of cognitive impairment.Conclusion: Inferring biological meaning from these observed curves is not valid without examining the mathematical phenomena of the relationship of incidence, mortality and prevalence. This approach allows an examination of the impact of varying mortality and incidence on the prevalence of dementia and cognitive impairment and will be useful in determining the potential impact of preventive strategies on the population. [ABSTRACT FROM AUTHOR]

Abstract Background Weaning of beef calves is a necessary husbandry practice and involves separating the calf from its mother, resulting in numerous stressful events including dietary change, social reorganisation and the cessation of the maternal-offspring bond and is often accompanied by housing. While much recent research has focused on the physiological response of the bovine immune system to stress in recent years, little is known about the molecular mechanisms modulating the immune response. Therefore, the objective of this study was to provide new insights into the molecular mechanisms underlying the physiological response to weaning at housing in beef calves using Illumina RNA-seq. Results The leukocyte transcriptome was significantly altered for at least 7 days following either housing or weaning at housing. Analysis of differentially expressed genes revealed that four main pathways, cytokine signalling, transmembrane transport, haemostasis and G-protein-coupled receptor (GPRC) signalling were differentially regulated between control and weaned calves and underwent significant transcriptomic alterations in response to weaning stress on day 1, 2 and 7. Of particular note, chemokines, cytokines and integrins were consistently found to be up-regulated on each day following weaning. Evidence for alternative splicing of genes was also detected, indicating a number of genes involved in the innate and adaptive immune response may be alternatively transcribed, including those responsible for toll receptor cascades and T cell receptor signalling. Conclusions This study represents the first application of RNA-Seq technology for genomic studies in bovine leukocytes in response to weaning stress. Weaning stress induces the activation of a number of cytokine, chemokine and integrin transcripts and may alter the immune system whereby the ability of a number of cells of the innate and adaptive immune system to locate and destroy pathogens is transcriptionally enhanced. Stress alters the homeostasis of the transcriptomic environment of leukocytes for at least 7 days following weaning, indicating long term effects of stress exposure in the bovine. The identification of gene signature networks that are stress activated provides a mechanistic framework to characterise the multifaceted nature of weaning stress adaptation in beef calves. Thus, capturing subtle transcriptomic changes provides insight into the molecular mechanisms that underlie the physiological response to weaning stress.

Abstract Background The effect of pre-weaning concentrate supplementation on peripheral distribution of leukocytes, functional activity of neutrophils, acute phase protein response, metabolic and behavioural response, and performance of abruptly weaned and housed beef calves was investigated. Calves were grazed with their dams until the end of the grazing season when they were weaned and housed (day (d) 0) in a concrete slatted floor shed, and offered grass silage ad libitum plus supplementary concentrates. Twenty-six days prior to weaning and housing, 20 singled suckled, pure-bred Simmental male (non-castrated), (n = 10, m) and female (n = 10, f) calves were assigned to one of two treatments (i) concentrate supplement (CS: n = 10 (5 m and 5 f), mean age (s.d.) 201 (12.8) d, mean weight (s.d.) 258 (20.2) kg) or (ii) no concentrate supplement (controls) (NCS: n = 10, (5 m and 5 f), mean age (s.d.) 201 (13.4) d, mean weight (s.d.) 257 (19.6) kg) pre-weaning. Results There was a treatment × sampling time interaction (P < 0.05) for percentage CD4+ and WC1+ (γδ T cells) lymphocytes and concentration of plasma globulin. On d 2, percentage CD4+ lymphocytes decreased (P < 0.001) in both treatments. Subsequently on d 7, percentage of CD4+ lymphocytes increased (P < 0.01) in CS compared with d 0, whereas percentage of CD4+ lymphocytes in NCS did not differ (P > 0.05) from d 0. On d 2, WC1+ lymphocytes decreased (P < 0.05) in both treatments but the decrease was greater (P <0.05) in NCS than CS. Subsequently, percentages did not differ (P > 0.05) from pre-weaning baseline. On d 2, the increase in concentration of globulin was greater (P < 0.05) in CS compared with NCS, and subsequently there was no difference between treatments. Pre-weaning ADG was 1.07 (s.e.m.) (0.26) kg and 0.99 (s.e.m.) (0.26) kg for CS and NCS, respectively. Post-weaning, CS calves spent more time lying compared with NCS calves. Conclusions Calves supplemented with concentrate prior to weaning had a lesser reduction in WC1+ lymphocytes, increased percentage CD4+ lymphocytes and concentration of total protein, and spent more time lying post-weaning, compared with non-supplemented calves.

Abstract Background The molecular mechanisms by which stress induces the development of pathologies remains unclear, although it is recognised that one of the major factors affecting health as a consequence of stress is the involvement of the neuroendocrine system. In cattle, a number of necessary husbandry practices have been shown to activate the stress response, yet very little is known about the impact these have at the molecular level. The objectives of the study were to characterise, in male and female beef calves, the immune response to weaning stress in bovine leukocytes at the physiological and molecular levels and to assess the difference between calves weaned in the presence of the dam and those weaned and penned away from the dam. Results Following exposure to weaning stress, total neutrophil number and neutrophil:lymphocyte (N:L) ratio increased (P < 0.01) in calves. Additionally, expression of pro-inflammatory cytokine genes, including IL-1β, IL-8, IFN-γ and TNFα, were up-regulated (P < 0.01). Furthermore, there was increased (P < 0.001) expression of the glucocorticoid receptor, GRα, the pro-apoptotic gene, Fas and the Gram-negative pattern recognition receptor, TLR4. Calves penned away from the dam post-weaning had increased (P < 0.01) neutrophil number and N:L ratio compared with calves penned next to the dam, and female calves had higher (P < 0.05) expression levels of IL-2, IL-8, IFN-γ and TNFα than male calves. Conclusions Weaning elicits an immediate and somewhat short-lived acute stress response in the calf. The effects serve to enhance, rather than suppress, the immune response by means of a heightened inflammatory response and cellular mobilization. The earlier and more profound increase in neutrophil number and N:L ratio together with reduced lymphocyte number in calves penned away compared with calves penned near their dams post-weaning suggests that the former may be more sensitive to weaning stress. The data also show a clear effect of gender in differential gene expression in response to stress with IFN-γ having increased expression in female calves compared with male calves over the course of the study. Additionally, this study has helped to characterise the inflammatory response to stress in calves and identify a number of novel candidate biomarkers suitable for investigation in future studies of stress.

Abstract Background Weaning involves the permanent separation of the calf from the dam and has been shown to be stressful for both. The objectives of this study were to characterise the effect of i) abrupt weaning and ii) subsequent housing on the extended physiological and immunological responses of beef cows. At weaning (day (d) 0, mean age of calf (s.d.) 212 (24.5) d), cows were abruptly separated from their calves and returned to the grazing area. After 35 d at pasture, cows were housed in a slatted floor shed and offered grass silage ad libitum plus a mineral-vitamin supplement daily. Rectal body temperature was recorded and blood samples were obtained on i) d 0 (weaning), 2, 7, 14, 21, 28, 35 and subsequently on ii) d 0 (housing), 2, 7, 14 and 21 for physiological, haematological and immunological measurements. Results Post-weaning, concentration of cortisol and dehydroepiandrosterone were unchanged (P > 0.05). Rectal body temperature, neutrophil number and neutrophil: lymphocyte ratio increased (P < 0.01) on d 2 compared with pre-weaning baseline. Lymphocyte and neutrophil number decreased (P < 0.05) on d 2 to 7 and d 7 to 21, respectively, compared with pre-weaning baseline. Interferon-γ production decreased (P < 0.05) on d 2 compared with pre-weaning baseline. An increase (P < 0.05) in acute phase proteins, fibrinogen and haptoglobin was evident on d 2 to 35 compared with pre-weaning baseline. Concentration of glucose increased on d 2 to 28, whereas non-esterified fatty acid decreased on d 2 to 35 compared with pre-weaning baseline. Post-housing, concentrations of cortisol, rectal body temperature, total leukocyte number, and glucose were unchanged (P > 0.05). On d 2 post-housing, neutrophil number and neutrophil: lymphocyte ratio increased (P < 0.05), whereas lymphocyte number and concentrations of dehydroepiandrosterone, fibrinogen and non-esterified fatty acid decreased (P < 0.05) compared with pre-housing baseline. Concentration of haptoglobin increased (P < 0.05) on d 14 to 21 post-housing. Conclusions A transitory increase in neutrophil number and decrease in lymphocyte number, increased neutrophil:lymphocyte ratio coupled with decreased interferon-γ production, and increased concentration of acute phase proteins indicate a stress response in cows post-weaning, whereas post-housing, changes were less marked.