Individual neurophysiological signatures of spontaneous rhythm processing.

When sensory input conveys rhythmic regularity, we can form predictions about the timing of upcoming events. Although rhythm processing capacities differ considerably between individuals, these differences are often obscured by participant- and trial-level data averaging procedures in M/EEG research. Here, we systematically assessed neurophysiological variability displayed by individuals listening to isochronous (1.54 Hz) equitone sequences interspersed with unexpected (amplitude-attenuated) deviant tones. Our approach aimed at revealing time-varying adaptive neural mechanisms for sampling the acoustic environment at multiple timescales. Rhythm tracking analyses confirmed that individuals encode temporal regularities and form temporal expectations, as indicated in delta-band (1.54 Hz) power and its anticipatory phase alignment to expected tone onsets. Zooming into tone- and participant-level data, we further characterized intra- and inter-individual variabilities in phase-alignment across auditory sequences. Further, individual modeling of beta-band tone-locked responses showed that a subset of auditory sequences was sampled rhythmically by superimposing binary (strong-weak; S-w), ternary (S-w-w) and mixed accentuation patterns. In these sequences, neural responses to standard and deviant tones were modulated by a binary accentuation pattern, thus pointing towards a mechanism of dynamic attending. Altogether, the current results point toward complementary roles of delta- and beta-band activity in rhythm processing and further highlight diverse and adaptive mechanisms to track and sample the acoustic environment at multiple timescales, even in the absence of task-specific instructions.

Non-hip and non-vertebral fractures: the neglected fracture sites.

SUMMARY: Non-hip, non-vertebral fractures (NHNVF) were compared with hip, vertebral and controls. NHNVF were younger and heavier than controls and hip/vertebral fractures in both men and women, respectively. Falls and prior fractures were less common in NHNVF than hip fractures. Glucocorticoid use was lower in NHNVF compared to vertebral fracture (VF) in men. INTRODUCTION: Although hip fracture (HF) and vertebral fractures (VF) receive the most attention in the literature and are the targeted sites for fracture prevention, non-hip, non-vertebral fracture (NHNVF) sites account for a greater proportion of fractures than the hip or vertebrae. This study aimed to assess risk factors for NHNVF and compare them with those for HF, VF and controls. METHODS: Incident fractures during 2005-2007 for men and 1994-1996 for women were identified using computerised keyword searches of radiological reports, and controls were selected at random from electoral rolls for participation in the Geelong Osteoporosis Study. Participants aged 60+ years were included in this study. RESULTS: Compared to controls, men and women with NHNVF were younger (ORs, 0.90, 95% CI 0.86-0.94; and 0.96, 0.93-0.98, respectively) and had a lower femoral neck bone mineral density (BMD) T-score (age-adjusted; difference [men] 0.383, P = 0.002; [women] 0.287, P = 0.001). Compared to HF, men and women with NHNVF were heavier (difference [men] 9.0 kg, P = 0.01; [women] 7.6 kg, P < 0.001). Heavier weight was also a risk factor for women with NHNVF compared to VF (1.03, 1.01-1.06). In men with NHNVF, falls (0.37, 0.14-0.97) and prior fractures (0.38, 0.15-0.98) were less common compared to HF; and glucocorticoid use was less common for NHNVF (0.30, 0.11-0.85) compared to VF. CONCLUSIONS: Given the high numbers of NHNVF sustained by men and women in this study, fracture prevention strategies should focus on individuals with high risk of sustaining these types of fractures, as well as on individuals who are more likely to sustain a HF or VF.

Calcaneal ultrasound reference ranges for Australian men and women: the Geelong Osteoporosis Study.

UNLABELLED: Heel ultrasound is a more portable modality for assessing fracture risk than dual-energy X-ray absorptiometry and does not use ionising radiation. Fracture risk assessment requires appropriate reference data to enable comparisons. This study reports the first heel ultrasound reference ranges for the Australian population. INTRODUCTION: This study aimed to develop calcaneal (heel) ultrasound reference ranges for the Australian adult population using a population-based random sample. METHODS: Men and women aged≥20 years were randomly selected from the Barwon Statistical Division in 2001-2006 and 1993-1997, respectively, using the electoral roll. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI) were measured at the heel using a Lunar Achilles Ultrasonometer. Gender-specific means and standard deviations for BUA, SOS and SI were calculated for the entire sample (men 20-93 years, n=1,104; women 20-92 years, n=914) and for participants aged 20-29 years (men, n=157; women, n=151). Associations between ultrasound measures and age were examined using linear regression. RESULTS: For men, mean±standard deviation BUA, SOS and SI were 118.7±15.8 dB/MHz, 1,577.0±43.7 m/s and 100.5±20.7, respectively; values for women were consistently lower (111.0±16.4 dB/MHz, P<0.001; 1,571.0±39.0 m/s, P=0.001; and 93.7±20.3, P<0.001, respectively). BUA was higher in young men compared with young women (124.5±14.4 vs 121.0±15.1 dB/MHz), but SOS (1,590.1±43.1 vs 1,592.5±35.0 m/s) and SI (108.0±19.9 vs 106.3±17.7) were not. The relationships between age and each ultrasound measure were linear and negative across the age range in men; associations were also negative in women but non-linear. CONCLUSION: These data provide reference standards to facilitate the assessment of fracture risk in an Australian population using heel ultrasound.

Patterns of treatment in Australian men following fracture.

UNLABELLED: This study aimed to describe treatment initiation rates for men who had recently sustained a fracture. Most (75.9%) men potentially eligible for subsidised treatment at the time of fracture remained untreated even after a subsequent fracture. INTRODUCTION: This study aimed to describe treatment initiation rates for men who had recently sustained a fracture. METHODS: The study was conducted as part of the Geelong Osteoporosis Study in south-eastern Australia. Men in the study area who had sustained an incident fracture in the period July 2006 to December 2007 were identified from hospital radiology reports. A self-report questionnaire was sent to eligible participants approximately 12 months after fracture. Respondents were asked for details of medications prescribed for 'osteoporosis/fracture/low bone mass' before and after fracture, and where applicable, reasons for cessation of treatment. We analysed the results for 109 men aged 50 years and older who had sustained fracture in the study period. RESULTS: Most (75.9%) men potentially eligible for subsidised treatment at the time of fracture remained untreated. Of the 87 men who were untreated, nine had osteoporosis at the hip and/or spine and 29 (26.6%) reported having sustained a low trauma prior fracture. CONCLUSIONS: Our findings are consistent with previously published data showing low rates of treatment initiation in men eligible for osteoporosis treatment. There appear to be barriers involving participants' and medical practitioners' knowledge, beliefs and attitudes regarding osteoporosis and treatment, as well as in the doctor-patient partnership in osteoporosis management. Establishment of clinical pathways for fracture management beyond orthopaedic care may be one of a range of appropriate responses.

Bone mineral density reference ranges for Australian men: Geelong Osteoporosis Study.

SUMMARY: A large population-based random sample of Australian white men was used to provide normative bone mineral density (BMD) data at multiple anatomical sites. The femoral neck BMD data are very similar to those obtained in USA non-Hispanic white males participating in the National Health and Nutrition Examination Survey III (NHANES III). The reference ranges will be suitable for similar populations. INTRODUCTION: To provide normative BMD data for Australian men derived from a large population-based random sample. METHODS: An age-stratified random sample of men was recruited from the Australian electoral rolls (n = 1,467 aged 20-97 years). BMD was quantified at multiple sites using Lunar densitometers. RESULTS: Age-related differences in BMD were best predicted by linear relationships at the spine and hip and by quadratic functions at the whole body and forearm. At the spine, a small age-related increase in mean BMD was observed. Although in the subset with no spinal abnormalities, there was a decrease of 0.003 g/cm(2) per year from age 20. At the hip sites, mean BMD decreased at 0.001-0.006 g/cm(2) per year from age 20. At the forearm and whole body, BMD peaked at 41-47 years. Apart from a small difference in men greater than or equal to 80 years, the Australian femoral neck BMD data are not different to those obtained in USA non-Hispanic white males participating in NHANES III and were generally similar to those of large studies from Canada (CaMos) and Spain. CONCLUSIONS: These data supply BMD reference ranges at multiple anatomical sites that will be applicable to white Australian men and similar populations such as USA non-Hispanic white men.

Morphometric vertebral fractures of the lower thoracic and lumbar spine, physical function and quality of life in men.

UNLABELLED: The epidemiology and sequelae of morphometric vertebral fracture (MVF) are poorly documented. We found that MVFs of the lower thoracic and lumbar spine were associated with poor quality of life and impaired physical function in men. We recommend that morphometric X-ray absorptiometry be included in routine requests for bone densitometry. INTRODUCTION: Vertebral fractures are sentinel events for osteoporosis. We aimed to compare quality of life and physical function in men with and without MVF. METHODS: Using morphometric X-ray absorptiometry (T10-L4), MVFs were identified in a random sample of men aged 20-93 years. Moderate and severe wedge, biconcave or compression deformities (>25% reduction in any vertebral height) were classified as MVFs. RESULTS: Of 1,147 men, MVFs were identified in 64. No MVFs were detected for men in their twenties. Prevalence was 1.5% for 30-39 years, 1.4% 40-49 years, 3.2% 50-59 years, 4.7% 60-69 years, 10.0% 70-79 years and 14.6% 80+ years. Among 555 men aged 60+ years, those with MVFs were twice as likely to have quality of life scores in the lowest tertile (age-adjusted OR = 2.35, 95%CI 1.24-4.45). MVFs were associated with lower mean age-adjusted physical activity scores [11.3 (95%CI 9.0-13.8) vs 14.0 (13.2-14.9), P = 0.04] and longer mean age-adjusted 'Up-&-Go' times [9.5 (8.9, 10.1) vs 8.9 (8.8, 9.1) s, P = 0.06]. CONCLUSION: Despite most men being unaware of their condition, MVFs were associated with poor quality of life and impaired physical function. We recommend that morphometric X-ray absorptiometry be included in routine requests for bone densitometry because detection of MVFs has important implications for osteoporosis management in men.

Inefficient procurement processes undermine access to medicines in the Western Cape Province of South Africa.

BACKGROUND: South Africa (SA) has experienced several stock-outs of life-saving medicines for the treatment of major chronic infectious and non-communicable diseases in the public sector. OBJECTIVE: To identify the causes of stock-outs and to illustrate how they undermine access to medicines (ATM) in the Western Cape Province, SA. METHODS: This qualitative study was conducted with a sample of over 70 key informants (frontline health workers, sub-structure and provincial health service managers). We employed the critical incident technique to identify significant occurrences in our context, the consequences of which impacted on access to medicines during a defined period. Stock-outs were identified as one such incident, and we explored when, where and why they occurred, in order to inform policy and practice. RESULTS: Medicines procurement is a centralised function in SA. Health service managers unanimously agreed that stock-outs resulted from the following inefficiencies at the central level: (i) delays in awarding of pharmaceutical tenders; (ii) absence of contracts for certain medicines appearing on provincial code lists; and (iii) suppliers' inability to satisfy contractual agreements. The recurrence of stock-outs had implications at multiple levels: (i) health facility operations; (ii) the Chronic Dispensing Unit (CDU), which prepacks medicines for over 300 000 public sector patients; and (iii) community-based medicines distribution systems, which deliver the CDU's prepacked medicines to non-health facilities nearer to patient homes. For instance, stock-outs resulted in omission of certain medicines from CDU parcels that were delivered to health facilities. This increased workload and caused frustration for frontline health workers who were expected to dispense omitted medicines manually. According to frontline health workers, this translated into longer waiting times for patients and associated dissatisfaction. In some instances, patients were asked to return for undispensed medication at a later date, which could potentially affect adherence to treatment and therapeutic outcomes. Stock-outs therefore undermined the intended benefits of ATM strategies. CONCLUSION: Addressing the procurement challenges, most notably timeous tender awards and supplier performance management, is critical for successful implementation of ATM strategies.

Serum leptin levels are associated with bone mass in nonobese women.

Both serum leptin and bone mineral density are positively correlated with body fat, generating the hypothesis that leptin may be a systemic and/or local regulator of bone mass. We investigated 214 healthy, nonobese Australian women aged 20-91 yr. Bone mineral content, projected bone area, and body fat mass were measured by dual energy x-ray absorptiometry and fasting serum leptin levels by RIA. Associations between bone mineral content (adjusted for age, body weight, body fat mass, and bone area) and the natural logarithm of serum leptin concentrations were analyzed by multiple regression techniques. There was a significant positive association at the lateral spine, two proximal femur sites (Ward's triangle and trochanter), and whole body (partial r(2) = 0.019 to 0.036; all P < 0.05). Similar trends were observed at the femoral neck and posterior-anterior-spine. With bone mineral density the dependent variable (adjusted for age, body weight, and body fat mass), the association with the natural logarithm of leptin remained significant at the lateral spine (partial r(2) = 0.030; P = 0.011), was of borderline significance at the proximal femur sites (partial r(2) = 0.012 to 0.017; P = 0.058 to 0.120), and was not significant at the other sites. Our results demonstrate an association between serum leptin levels and bone mass consistent with the hypothesis that circulating leptin may play a role in regulating bone mass.

Fracture thresholds revisited. Geelong Osteoporosis Study.

Osteoporosis, in the absence of fracture, is defined as a deficit in bone mineral density (BMD) of 2.5 SD or more below the young adult reference mean in postmenopausal Caucasian populations. BMD is a measure of fracture risk but not the sole predictor. We have assessed a combination of easily accessible measures of age, height, weight, and BMD to improve fracture risk assessment. Women with low trauma fractures and a control group were recruited from south-eastern Australia. Discriminant analysis derived multivariate equations that assessed fracture risk. Age was not in the best models at the spine and forearm sites. Weight and height contributed to the relationship for the forearm sites only. At the proximal femur, the BMD level that separates fracture cases from nonfracture cases, increases with age. These separation levels of BMD were higher than the WHO's level of osteoporosis (T-score < -2.5 SD) at ages older than 62 years. This increasing BMD threshold with age suggests that other age-related risk factors assume increasing importance among the elderly.

A polymorphism in the tumor necrosis factor-alpha gene promoter region may predispose to a poor prognosis in COPD.

STUDY OBJECTIVES: To determine whether the adenine (A)-guanine (G) substitution polymorphism at position - 308 on the tumor necrosis factor-alpha gene confers susceptibility to COPD or to the development of a more severe form of disease. DESIGN: A cross-sectional study was undertaken to compare the frequency of the A allele in a group of 106 patients with COPD with that in a control population (n = 99). Patients were followed up prospectively for a period of 2 years. PARTICIPANTS AND SETTING: Participants included 106 COPD patients recruited from a respiratory outpatient clinic and 99 control subjects recruited from patients admitted for cardiac catheterization. MEASUREMENTS AND RESULTS: DNA was extracted from venous blood, and each subject was genotyped for the polymorphism by polymerase chain reaction amplification and restriction digestion using Nco1. There was no increased frequency of the A allele in patients compared to control subjects. AA homozygous patients had less reversible airflow obstruction (p<0.05) and a significantly greater mortality (both all-cause and respiratory deaths) on follow-up (p<0.001), despite a shorter cigarette smoking history. CONCLUSIONS: This study suggests that homozygosity for this A allele predisposes to more severe airflow obstruction and a worse prognosis in COPD.

The effects of carbohydrate restriction in patients with diet-controlled gestational diabetes.

OBJECTIVE: To determine the effect of carbohydrate restriction on perinatal outcome in patients with diet-controlled gestational diabetes mellitus (GDM). METHODS: Women with diet-controlled GDM were divided non-randomly into two groups based on their dietary carbohydrate content: those with low dietary carbohydrate content (below 42%) and those with high dietary carbohydrate content (exceeding 45%). Subjects kept dietary accounts and were followed with daily fasting and postprandial glucose assessments. Subjects also were tested daily for urinary ketones. Glycosylated hemoglobin, mean fasting and postprandial glucose values, incidence of macrosomia and large for gestational age (LGA) infants, cesarean deliveries for cephalopelvic disproportion and macrosomia, and need for insulin therapy were compared between the groups. RESULTS: The two groups were identical in terms of demographic characteristics. Significant reductions in the postprandial glucose values were seen among subjects in the low-carbohydrate group (P < .04). Fewer subjects in the low-carbohydrate group required the addition of insulin for glucose control (P < .047; relative risk [RR] 0.14; 95% confidence interval [CI] 0.02, 1.00). The incidence of LGA infants was significantly lower in the low-carbohydrate group (P < .035; RR 0.22; 95% CI 0.05, 0.91). Subjects in the low carbohydrate group also had a lower rate of cesarean deliveries for cephalopelvic disproportion and macrosomia (P < .037; RR 0.15; 95% CI 0.04, 0.94). CONCLUSION: Carbohydrate restriction in patients with diet-controlled GDM results in improved glycemic control, less need for insulin therapy, a decrease in the incidence LGA infants, and a decrease in cesarean deliveries for cephalopelvic disproportion and macrosomia.

Causal Role of Xylella fastidiosa in Oleander Leaf Scorch Disease.

ABSTRACT A lethal leaf scorch disease of oleander (Nerium oleander) appeared in southern California in 1993. A bacterium, Xylella fastidiosa, was detected by culturing, enzyme-linked immunoassay, and polymerase chain reaction in most symptomatic plants but not in symptomless plants or negative controls. Inoculating oleanders mechanically with X. fastidiosa cultures from diseased oleanders caused oleander leaf scorch (OLS) disease. The bacterium was reisolated from inoculated plants that became diseased. Three species of xylem sap-feeding leafhoppers transmitted the bacterium from oleander to oleander. The bacterium multiplied, moved systemically, and caused wilting in Madagascar periwinkle (Catharanthus rosea) and leaf scorch in periwinkle (Vinca major) in a greenhouse after inoculation with needle puncture. No bacterium was reisolated from grapevine (Vitis vinifera), peach (Prunus persica), olive (Olea europaea), California blackberry (Rubus ursinus), or valley oak (Quercus lobata) mechanically inoculated with OLS strains of X. fastidiosa. A 500-bp sequence of the 16S-23S ribosomal intergenic region of oleander strains showed 99.2% identity with Pierce's disease strains, 98.4% identity with oak leaf scorch strains, and 98.6% identity with phony peach, plum leaf scald, and almond leaf scorch strains.

Accuracy of self-monitoring of blood glucose: impact on diabetes management decisions during pregnancy.

PURPOSE: This study tested the hypothesis that the accuracy of self-monitoring of blood glucose (SMBG) values of patients with diabetes during pregnancy deviates substantially from reference values. METHODS: The patients' glucose values were measured on 6 different SMBG meters; reference values were from the HemoCue B Glucose Analyzer. Over a 5-year period, 1973 comparisons between SMBG values and reference values were recorded during clinic visits and used for this study. Data were analyzed for percent of values that varied more than +/- 10.5% and +/- 15.5% from the reference value. Out-of-range data at each variance level were analyzed to determine the impact on medical management if decisions were based solely on SMBG values. RESULTS: One third of SMBG readings deviated significantly, which could adversely affect treatment for half of these patients if diabetes management was based on SMBG values. At the 10.5% deviation level, 34% of SMBG meter readings were out of range; 54% of these would have implied erroneous treatment. At the 15.5% deviation level, 18% were out of range; 63% of these would have implied erroneous management. CONCLUSIONS: The accuracy of home meters should be verified at regular intervals, and SMBG values should not be the sole criterion for diabetes management during pregnancy.

Prevalence of osteoporosis in Australian women: Geelong Osteoporosis Study.

To evaluate the prevalence of osteoporosis at various sites among Australian women, cross-sectional bone mineral density (BMD) data for adult females was obtained from an age-stratified population-based sample (n = 1494; 20-94 yr) drawn at random from the Barwon Statistical Division, a population characteristic of Australia. Age- and weight- (and for three sites, height) matched reference ranges for BMD at the lumbar spine, proximal femur, forearm, and total body were developed using regression techniques. The cutoff BMD level for osteoporosis at the PA spine was 0. 917g/cm(2) and 0.713 g/cm(2) at the femoral neck according to the World Health Organization (WHO) guidelines. The upper cutoff level for osteopenia was 1.128 g/cm(2) at the PA spine and 0.913g/cm(2) for the femoral neck. The proportion of Australian women categorized as having osteoporosis at the PA spine, femoral neck, or midforearm ranged from 0.9% among those aged 40-44 yr to 87.0% for those older than 79 yr. This study provides reference data representative of the Australian female population. A large proportion of elderly Australian women has osteoporosis according to the WHO guidelines.

Assessment of fracture risk: value of random population-based samples--the Geelong Osteoporosis Study.

Fracture risk is determined by bone mineral density (BMD). The T-score, a measure of fracture risk, is the position of an individual's BMD in relation to a reference range. The aim of this study was to determine the magnitude of change in the T-score when different sampling techniques were used to produce the reference range. Reference ranges were derived from three samples, drawn from the same region: (1) an age-stratified population-based random sample, (2) unselected volunteers, and (3) a selected healthy subset of the population-based sample with no diseases or drugs known to affect bone. T-scores were calculated using the three reference ranges for a cohort of women who had sustained a fracture and as a group had a low mean BMD (ages 35-72 yr; n = 484). For most comparisons, the T-scores for the fracture cohort were more negative using the population reference range. The difference in T-scores reached 1.0 SD. The proportion of the fracture cohort classified as having osteoporosis at the spine was 26, 14, and 23% when the population, volunteer, and healthy reference ranges were applied, respectively. The use of inappropriate reference ranges results in substantial changes to T-scores and may lead to inappropriate management.

Design of the cyclops flap for chest-wall reconstruction.

The cyclops flap is a little-known but not forgotten alternative in chest-wall reconstruction for women. Female patients having a large, pendulous breast with a contralateral adjacent defect may be reconstructed by this technique. The flap derives its name from the repositioning of the remaining nipple to the center of the chest. The design of the flap is described. By knowing the width and length of the defect, the surgeon can design incisions on the remaining breast tissue that will allow the flap to advance easily, reliably filling the defect. The flap is an axial-pattern flap nourished by the lateral thoracic artery and the variable external mammary artery. This arterial inflow will serve the medial portion of the flap. The operation is straightforward and predictable. In using this design scheme three times in the last two years, there have been no complications. There is little discomfort after surgery. Occasionally, patients will benefit from this reconstructive option.

The significance of leukemia and lymphoma cells in cerebrospinal fluid contaminated by blood containing malignant cells: a probabilistic approach based on the Poisson frequency distribution.

The significance of malignant cells in a body fluid is often difficult to determine if that fluid is contaminated by blood containing malignant cells. This problem is most often seen in examination of CSF from patients with lymphoma or leukemia. We suggest a statistical model of this problem in which the numbers of malignant cells in the blood and the fluid specimen are related to the number of red blood cells. Using the Poisson distribution, the probability of finding the observed number of malignant cells in the fluid is calculated and used as the basis for suggesting whether these cells are likely to represent contamination effect or true involvement of the fluid by the malignancy. The limitations and applicability of this process are discussed.