Neuromorphic Tactile Edge Orientation Classification in an Unsupervised Spiking Neural Network.

Dexterous manipulation in robotic hands relies on an accurate sense of artificial touch. Here we investigate neuromorphic tactile sensation with an event-based optical tactile sensor combined with spiking neural networks for edge orientation detection. The sensor incorporates an event-based vision system (mini-eDVS) into a low-form factor artificial fingertip (the NeuroTac). The processing of tactile information is performed through a Spiking Neural Network with unsupervised Spike-Timing-Dependent Plasticity (STDP) learning, and the resultant output is classified with a 3-nearest neighbours classifier. Edge orientations were classified in 10-degree increments while tapping vertically downward and sliding horizontally across the edge. In both cases, we demonstrate that the sensor is able to reliably detect edge orientation, and could lead to accurate, bio-inspired, tactile processing in robotics and prosthetics applications.

Antidepressant use and 10-year incident fracture risk: the population-based Canadian Multicentre Osteoporosis Study (CaMoS).

UNLABELLED: We used data from a large, prospective Canadian cohort to assess the association between selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) and fracture. We found an increased risk of fractures in individuals who used SSRI or SNRI, even after controlling for multiple risk factors. INTRODUCTION: Previous studies have suggested an association between SSRIs and increasing risk of fragility fractures. However, the majority of these studies were not long-term analyses or were performed using administrative data and, thus, could not fully control for potential confounders. We sought to determine whether the use of SSRIs and SNRIs is associated with increased risk of fragility fracture, in adults aged 50 + . METHODS: We used data from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective randomly selected population-based community cohort; our analyses focused on subjects aged 50+. Time to event methodology was used to assess the association between SSRI/SNRI use, modeled time-dependently, and fragility fracture. RESULTS: Among 6,645 subjects, 192 (2.9%) were using SSRIs or/and SNRIs at baseline. During the 10-year study period, 978 (14.7%) participants experienced at least one fragility fracture. In our main analysis, SSRI/SNRI use was associated with increased risk of fragility fracture (hazard ratio (HR), 1.88; 95% confidence intervals (CI), 1.48-2.39). After controlling for multiple risk factors, including Charlson score, previous falls, and bone mineral density hip and lumbar bone density, the adjusted HR for current SSRI/SNRI use remained elevated (HR, 1.68; 95% CI, 1.32-2.14). CONCLUSIONS: Our results lend additional support to an association between SSRI/SNRI use and fragility fractures. Given the high prevalence of antidepressants use, and the impact of fractures on health, our findings may have a significant clinical impact.

The effect of proton pump inhibitors on fracture risk: report from the Canadian Multicenter Osteoporosis Study.

UNLABELLED: A large Canadian cohort was studied over 10 years to see if proton pump inhibitor (PPI) use increased the risk of sustaining a fragility fracture. We found an increased risk of fracture in individuals who used PPIs. The risk remained after controlling for other known fracture risk factors. INTRODUCTION: Multiple retrospective studies have linked proton pump inhibitor use with increased risk of fragility fracture. We prospectively studied the association between PPI use and fracture in a large cohort over a 10-year period while controlling for known fracture risk factors. METHODS: We studied 9,423 participants in the Canadian Multicenter Osteoporosis Study. The cohort was formed in 1995-1997 and followed for 10 years with monitoring for incident nontraumatic fracture and PPI use. Cox regression analyses were used to assess the association between PPI use and incident fracture risk. RESULTS: PPI use, coded as a time-dependent variable, was associated with a shorter time to first nontraumatic fracture, hazard ratio (HR)=1.75 (95% confidence interval (CI) 1.41-2.17, p<0.001). After controlling for multiple risk factors, including femoral neck bone density, the association remained significant, HR=1.40 (95% CI 1.11-1.77, p=0.004). Similar results were obtained after controlling for bisphosphonate use, using PPI "ever" use, or when the outcome was restricted to hip fracture. CONCLUSIONS: In this large prospective population-based cohort study, we found an association between PPI use and increased risk of fragility fracture. Although the increased risk found was modest, this finding is important, given the high prevalence of PPI use and the excess morbidity and mortality associated with osteoporosis-related fractures.

Fragility fractures and the osteoporosis care gap in women: the Canadian Multicentre Osteoporosis Study.

UNLABELLED: Canadian women over 50 years old were studied over a 10-year period to see if those who sustained a fracture (caused by minimal trauma) were receiving the recommended osteoporosis therapy. We found that approximately half of these women were not being treated, indicating a significant care gap in osteoporosis treatment. INTRODUCTION: Prevalent fragility fracture strongly predicts future fracture. Previous studies have indicated that women with fragility fractures are not receiving the indicated treatment. We aimed to describe post fracture care in Canadian women using a large, population-based prospective cohort that began in 1995-1997. METHODS: We followed 5,566 women over 50 years of age from across Canada over a period of 10 years in the Canadian Multicentre Osteoporosis Study. Information on medication use and incident clinical fragility fractures was obtained during a yearly questionnaire or interview and fractures were confirmed by radiographic/medical reports. RESULTS: Over the 10-year study period, 42-56% of women with yearly incident clinical fragility fractures were not treated with an osteoporosis medication. During year 1 of the study, 22% of the women who had experienced a fragility fracture were on treatment with a bisphosphonate and 26% were on hormone therapy (HT). We were not able to differentiate HT use for menopause symptoms vs osteoporosis. Use of bisphosphonate therapy increased over time; odds ratio (OR) for use at year 10 compared to use at year 1 was 3.65 (95% confidence interval (CI) 1.83-7.26). In contrast, HT use declined, with an OR of 0.07 (95%CI 0.02-0.24) at year 10 compared to year 1 of the study. CONCLUSION: In a large population-based cohort study, we found a therapeutic care gap in women with osteoporosis and fragility fractures. Although bisphosphonate therapy usage improved over time, a substantial gap remains.

Fracture prediction and calibration of a Canadian FRAX® tool: a population-based report from CaMos.

UNLABELLED: A new Canadian WHO fracture risk assessment (FRAX®) tool to predict 10-year fracture probability was compared with observed 10-year fracture outcomes in a large Canadian population-based study (CaMos). The Canadian FRAX tool showed good calibration and discrimination for both hip and major osteoporotic fractures. INTRODUCTION: The purpose of this study was to validate a new Canadian WHO fracture risk assessment (FRAX®) tool in a prospective, population-based cohort, the Canadian Multicentre Osteoporosis Study (CaMos). METHODS: A FRAX tool calibrated to the Canadian population was developed by the WHO Collaborating Centre for Metabolic Bone Diseases using national hip fracture and mortality data. Ten-year FRAX probabilities with and without bone mineral density (BMD) were derived for CaMos women (N = 4,778) and men (N = 1,919) and compared with observed fracture outcomes to 10 years (Kaplan-Meier method). Cox proportional hazard models were used to investigate the contribution of individual FRAX variables. RESULTS: Mean overall 10-year FRAX probability with BMD for major osteoporotic fractures was not significantly different from the observed value in men [predicted 5.4% vs. observed 6.4% (95%CI 5.2-7.5%)] and only slightly lower in women [predicted 10.8% vs. observed 12.0% (95%CI 11.0-12.9%)]. FRAX was well calibrated for hip fracture assessment in women [predicted 2.7% vs. observed 2.7% (95%CI 2.2-3.2%)] but underestimated risk in men [predicted 1.3% vs. observed 2.4% (95%CI 1.7-3.1%)]. FRAX with BMD showed better fracture discrimination than FRAX without BMD or BMD alone. Age, body mass index, prior fragility fracture and femoral neck BMD were significant independent predictors of major osteoporotic fractures; sex, age, prior fragility fracture and femoral neck BMD were significant independent predictors of hip fractures. CONCLUSION: The Canadian FRAX tool provides predictions consistent with observed fracture rates in Canadian women and men, thereby providing a valuable tool for Canadian clinicians assessing patients at risk of fracture.

Hair analysis provides a historical record of cortisol levels in Cushing's syndrome.

The severity of Cushing's Syndrome (CS) depends on the duration and extent of the exposure to excess glucocorticoids. Current measurements of cortisol in serum, saliva and urine reflect systemic cortisol levels at the time of sample collection, but cannot assess past cortisol levels. Hair cortisol levels may be increased in patients with CS, and, as hair grows about 1 cm/month, measurement of hair cortisol may provide historical information on the development of hypercortisolism. We attempted to measure cortisol in hair in relation to clinical course in six female patients with CS and in 32 healthy volunteers in 1 cm hair sections. Hair cortisol content was measured using a commercially available salivary cortisol immune assay with a protocol modified for use with hair. Hair cortisol levels were higher in patients with CS than in controls, the medians (ranges) were 679 (279-2500) and 116 (26-204) ng/g respectively (P<0.001). Segmental hair analysis provided information for up to 18 months before time of sampling. Hair cortisol concentrations appeared to vary in accordance with the clinical course. Based on these data, we suggest that hair cortisol measurement is a novel method for assessing dynamic systemic cortisol exposure and provides unique historical information on variation in cortisol, and that more research is required to fully understand the utility and limits of this technique.

Oral opioids for chronic non-cancer pain: higher prevalence of hypogonadism in men than in women.

The effect of chronic oral opioids on hypothalamus-pituitary-gonadal axis in women, and on bone mineral density (BMD) in men and women is not known. The objective of this cross-sectional study was to determine the effect of long-term oral opioids on gonadal status and BMD in male and female patients with chronic non-cancer pain (CNCP). We included 26 community-dwelling CNCP patients, 12 men and 14 premenopausal women, treated with oral opioids for at least one year. We obtained Visual Analogue Scale for pain score, BMD and plasma LH and FSH in all patients; menstrual history and estradiol in women; free androgen index and total and free testosterone in men. Men were older then women (p<0.05) and had used opioids for a longer period (7.2+/-3.8 and 4.1+/-1.8 years, respectively; p<0.05), but there was no difference in opioid dose or pain score between sexes. The prevalence of hypogonadism was high in men (75%), while only 21% of the women reported oligo- or amenorrhea indicating hypogonadism (P<0.01, between sexes). Osteopenia was found in 50% of men and 21% of women (p=NS). We conclude that in CNCP patients receiving chronic opioid therapy there is a much higher prevalence of hypogonadism in men then in women. This needs to be considered clinical practice.

Elevated content of cortisol in hair of patients with severe chronic pain: a novel biomarker for stress.

Hair analysis has been used to reflect long-term systemic exposure to exogenous drugs and toxins. Several studies have demonstrated the feasibility of measuring endogenous steroid hormones, e.g. cortisol, in hair. Recently, a study in macaques showed a significant increase in hair cortisol levels induced by stress. We explored whether hair cortisol levels may be used as a biomarker for long-term stress in humans. Patients with severe chronic pain, aged 18 years or older, receiving opioid treatment for at least one year were recruited. Controls were non-obese (body mass index, BMI < 30 mg/kg(2)) adults. The Perceived Stress Scale (PSS) questionnaire was used to assess perceived stress over the last 4 weeks. A hair sample was obtained from the vertex posterior. Cortisol was measured using an enzyme-linked immunosorbent assay. We included fifteen patients (nine females and six males) and 39 non-obese control subjects (20 females, 19 males). PSS scores (median and range) were significantly higher in chronic pain patients (24: 12-28) than in controls (12: 3-31)(P < 0.001). Hair cortisol contents (median and range) were significantly greater in chronic pain patients (83.1: 33.0-205 g/mg) than in controls (46.1: 27.2-200 pg/mg) (P < 0.01). We conclude that hair cortisol contents are increased in patients with major chronic stress. Measurement of cortisol levels in hair constitutes a novel biomarker of prolonged stress.

Epidemiology of gallbladder cancer and trends in cholecystectomy rates in Scotland, 1968-1998.

The aim of this study was to describe the epidemiology of gallbladder cancer in Scotland during the last 30 years. A secondary aim was to describe trends in cholecystectomy rates because it has been suggested that changing rates of cholecystectomy for benign gallbladder disease may be influencing the epidemiology of gallbladder cancer. A retrospective analysis of cancer registration and mortality (gallbladder cancer) and hospital discharge (cholecystectomy) data from Scotland in 1968-1998 was carried out. In Scotland the incidence of, and mortality from, gallbladder cancer have been falling in women since at least 1968, and in men since the late 1980s. Whilst overall survival remains poor, survival in older patients may have improved recently, and survival is better in patients from affluent areas. Cholecystectomy rates increased until 1977 then fell until the introduction of laparoscopic surgery caused them to return to the rates previously observed. The current declining incidence of gallbladder cancer in Scotland is probably, in part, related to the increasing cholecystectomy rates seen prior to 1977. Further studies addressing changes in stage at diagnosis and treatment provided are required to investigate the recent apparent improvement in survival of elderly gallbladder cancer patients.

Do increases in mortality from intrahepatic cholangiocarcinoma reflect a genuine increase in risk? Insights from cancer registry data in Scotland.

The mortality from intrahepatic cholangiocarcinoma has increased recently in England and Wales and elsewhere. This study aims to examine recent trends in the incidence of intrahepatic cholangiocarcinoma in Scotland, to assess the extent to which changes in diagnostic practice may be influencing the observed trends, and to consider whether the results are compatible with a genuine increase in the risk of this cancer. Cancer registration (intrahepatic cholangiocarcinoma and anatomically adjacent cancers) data from Scotland 1968-1997 were analysed, including examination of trends in the percentage of cases recorded as being microscopically-verified. Since the late 1960s, the incidence of intrahepatic cholangiocarcinoma has increased approximately eight-fold in both sexes in Scotland. However, the proportion of cases verified microscopically has decreased substantially since the late 1970s, presumably due to an increasing reliance on radiological imaging for diagnosis. Despite this change in diagnostic practice, the incidence of microscopically-verified intrahepatic cholangiocarcinoma has also increased. While changes in diagnostic practice and misclassification could explain, at least part of, the observed increase in incidence of intrahepatic cholangiocarcinoma, a genuine increase in the risk of this cancer in the Scottish population seems probable. Further work is indicated to examine international trends in incidence, and to assess whether incidence differs within countries according to characteristics such as area of residence, socio-economic status, ethnic origin or occupation.

Socioeconomic status and risk of adenocarcinoma of the oesophagus and cancer of the gastric cardia in Scotland.

The incidence of oesophageal adenocarcinoma and gastric cardia cancer increased strikingly in Scotland between 1977 and 1996. In contrast to other cancers of the oesophagus and stomach, which showed a clear relationship with socioeconomic status, no trend was evident for oesophageal adenocarcinoma or gastric cardia cancer during 1987-1996.

Rising incidence of prostate cancer in Scotland: increased risk or increased detection?

OBJECTIVE: To assess the extent to which the increasing incidence of prostate cancer in Scotland can be explained by increased detection, particularly through transurethral resection of the prostate (TURP) and use of the prostate-specific antigen (PSA) test. Subjects and methods This population-based study was confined to men resident in Scotland and aged > or =50 years. Temporal trends were examined in age-specific and age-standardized incidence, mortality and TURP rates, and PSA testing rates during 1981-1996. Also analysed were the geographical variations in age-standardized incidence and mortality rates during two distinct periods, 1984-1986 (before PSA testing) and 1994-1996 (after PSA testing). Finally, incidence rates and relative survival at 5 years were calculated by age group and 5-year periods of diagnosis during 1968-1992. RESULTS: The incidence of prostate cancer in men aged > or = 50 years increased from an age-standardized rate of 142.0 per 100 000 in 1981 to 240.9 in 1996, with the steepest increase occurring between 1992 and 1993. The mortality rate increased similarly until 1993, but was relatively stable thereafter, falling slightly in 1996. In 1981-1988, incidence rates were closely correlated with TURP rates (r = 0.98, P<0.001). In 1989-1996, incidence was closely correlated with PSA testing rates (r = 0.98, P<0.001). By 1994-1996, incidence rates varied substantially between Scottish mainland health boards (range 167.7-303.0 per 100 000), with much less variation in mortality rates (90.7-110.0). Relative survival has increased recently in all age groups although, in the era before PSA testing, survival was reasonably stable despite increasing incidence. CONCLUSION: Although there may have been a true increase in risk, much of the observed increase in the incidence of prostate cancer in Scotland between 1981 and 1996 has been caused by increased detection, leading recently to considerable variation among different areas of the country. The extent to which this represents the early diagnosis of tumours which would eventually cause symptoms or be life-threatening, or detection of latent disease which would never have become symptomatic, is not clear. There is no evidence so far that the increased incidence is associated with any substantial reduction in mortality.

Composite tissue (limb) allografts in rats. I. Dose-dependent increase in survival with cyclosporine.

The dose-response effect of cyclosporine on rat limb transplant prolongation was investigated across the LBN-to-LEW histocompatibility barrier. This composite tissue allograft model has been shown to represent a strong transplantation barrier. Median limb allograft survival times increased in a dose-dependent manner with low cyclosporine doses, and then reached a plateau at higher levels. The cyclosporine dose that produced half-maximal survival based on a 20-day treatment was only 3.7 mg/kg/day. Histopathology revealed that the rejection process was distinctly different in limb allografts treated with cyclosporine compared with non-cyclosporine-treated controls. Rejection appeared to be delayed or partly arrested in certain areas of cyclosporine-treated limb allografts. These studies represent an initial step in laying the experimental foundation for clinical transplantation of composite tissue allografts using cyclosporine-induced immune suppression.

Composite tissue (limb) allografts in rats. II. Indefinite survival using low-dose cyclosporine.

Cyclosporine has reawakened interest in transplantation of peripheral composite tissue allografts (CTA) of skin, muscle, bone, vessel, and nerves. The purpose of this study was to examine whether cyclosporine could produce indefinite survival of CTA. Two groups of LEW recipients of LBN limb transplants were given different long-term treatments of cyclosporine. Tolerance was achieved in many of the animals. Several possibilities for the mechanism of this tolerance are discussed.