Cost-benefit analysis of controlling rabies: placing economics at the heart of rabies control to focus political will.

Rabies is an economically important zoonosis. This paper describes the extent of the economic impacts of the disease and some of the types of economic analyses used to understand those impacts, as well as the trade-offs between efforts to manage rabies and efforts to eliminate it. In many cases, the elimination of rabies proves more cost-effective over time than the continual administration of postexposure prophylaxis, animal testing and animal vaccination. Economic analyses are used to inform and drive policy decisions and focus political will, placing economics at the heart of rabies control.

La rage est une zoonose importante au plan économique. Les auteurs décrivent la portée de l'impact économique de la rage et présentent quelques modèles d'analyse économique utilisés pour comprendre ces effets ; ils analysent également les compromis à trouver entre les efforts consacrés à la gestion de la rage et ceux dédiés à son élimination. Dans bien des cas, il est plus rentable sur le long terme d'éliminer la rage que de procéder à la gestion continue de la prophylaxie post-exposition chez l'homme et au dépistage et à la vaccination des animaux. Les analyses économiques servent à documenter et à orienter les décisions concernant les mesures à prendre afin de mobiliser la volonté politique nécessaire, en plaçant l'économie au coeur de la lutte contre la rage.

La rabia es una zoonosis que reviste importancia económica. Los autores exponen la magnitud del impacto económico de la enfermedad y algunas de las modalidades de análisis económico utilizadas para aprehender esas consecuencias, así como el juego de equilibrios entre las medidas de gestión de la rabia y las actividades destinadas a eliminarla. En muchos casos, la eliminación de la enfermedad ofrece a la larga mayor eficacia, en relación con el costo, que la continua labor de administración de profilaxis tras exposición, realización de pruebas en animales y vacunación de estos. Los análisis económicos sirven para fundamentar y encauzar las decisiones de planificación y para aglutinar la voluntad política, haciendo de los aspectos económicos un eje de la lucha contra la rabia.

Effects of total and regional fat loss on plasma CRP and IL-6 in overweight and obese, older adults with knee osteoarthritis.

OBJECTIVE: To describe associations between total and regional body fat mass loss and reduction of systemic levels of inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) in obese, older adults with osteoarthritis (OA), undergoing intentional weight loss. DESIGN: Data come from a single-blind, 18-month, randomized controlled trial in adults (age: 65.6 ± 6.2; Body mass index (BMI): 33.6 ± 3.7) with knee OA. Participants were randomized to diet-induced weight loss plus exercise (D + E; n = 150), diet-induced weight loss-only (D; n = 149), or exercise-only (E; n = 151). Total body and region-specific (abdomen and thigh) fat mass were measured at baseline and 18 months. High-sensitivity CRP and IL-6 were measured at baseline, six and 18 months. Intervention effects were assessed using mixed models and associations between inflammation and adiposity were compared using logistic and mixed linear regression models. RESULTS: Intentional total body fat mass reduction was associated with significant reductions in log-adjusted CRP (ß = 0.06 (95% CI = 0.04, 0.08) mg/L) and IL-6 (ß = 0.02 (95% CI = 0.01, 0.04) pg/mL). Loss of abdominal fat volume was also associated with reduced inflammation, independent of total body fat mass; although models containing measures of total adiposity yielded the best fit. The odds of achieving clinically desirable levels of CRP (<3.0 mg/L) and IL-6 (<2.5 pg/mL) were 3.8 (95% CI = 1.6, 8.9) and 2.2 (95% CI = 1.1, 4.6), respectively, with 5% total weight and fat mass loss. CONCLUSIONS: Achievement of clinically desirable levels of CRP and IL-6 more than double with intentional 5% loss of total body weight and fat mass. Global, rather than regional, measures of adiposity are better predictors of change in inflammatory burden. CLINICAL TRIAL REGISTRATION NUMBER: NCT00381290.

Influence of age, sex and genetic factors on the human brain.

We report effects of age, age(2), sex and additive genetic factors on variability in gray matter thickness, surface area and white matter integrity in 1,010 subjects from the Genetics of Brain Structure and Function Study. Age was more strongly associated with gray matter thickness and fractional anisotropy of water diffusion in white matter tracts, while sex was more strongly associated with gray matter surface area. Widespread heritability of neuroanatomic traits was observed, suggesting that brain structure is under strong genetic control. Furthermore, our findings indicate that neuroimaging-based measurements of cerebral variability are sensitive to genetic mediation. Fundamental studies of genetic influence on the brain will help inform gene discovery initiatives in both clinical and normative samples.

Segmentation of synchrotron radiation micro-computed tomography images using energy minimization via graph cuts.

The research on applications of segmentation algorithms to Synchrotron Radiation X-Ray micro-Computed Tomography (SR-µCT) is an open problem, due to the interesting and well-known characteristics of SR images, such as the phase contrast effect. The Energy Minimization via Graph Cuts (EMvGC) algorithm represents state-of-art segmentation algorithm, presenting an enormous potential of application in SR-µCT imaging. We describe the application of the algorithm EMvGC with swap move for the segmentation of bone images acquired at the ELETTRA Laboratory (Trieste, Italy).

Phase contrast X-ray synchrotron imaging for assessing external and internal morphology of Rhodnius prolixus.

PhC-SR-µCT is a nondestructive technique that allows the microanatomical investigations and 3D images reconstructions. This technique is performed in blood sucker, Rhodnius prolixus--one of the most important insect vectors of Trypanosoma cruzi, ethiologic agent of Chagas' disease in Latin America--was able to provide excellent information about the microanatomy of the thorax and head allowing a new tool for further studies of development and physiology of triatomine by a non-invasive method of observation.

Insulin resistance, beta cell dysfunction and visceral adiposity as predictors of incident diabetes: the Insulin Resistance Atherosclerosis Study (IRAS) Family study.

AIMS/HYPOTHESIS: Central obesity, insulin resistance and beta cell dysfunction are independent risk factors for incident type 2 diabetes, although few studies have used detailed measures of these disorders. Our objective was to study the association of directly measured visceral and subcutaneous adipose tissue (VAT, SAT), insulin sensitivity (S (I)) and the acute insulin response (AIR) with incident type 2 diabetes. METHODS: Participants were 1,230 Hispanic-Americans and African-Americans in the Insulin Resistance Atherosclerosis Study (IRAS) Family Study who were free of type 2 diabetes at baseline (2000-2002). S (I) and AIR were determined from frequently sampled IVGTTs with minimal model analysis. VAT and SAT were determined by computed tomography. Impaired fasting glucose and type 2 diabetes were defined according to American Diabetes Association criteria. RESULTS: Incident type 2 diabetes was diagnosed in 90 participants after 5 years. After adjustment for age, sex, ethnicity, centre, impaired fasting glucose, triacylglycerol, HDL-cholesterol and systolic BP, both S(I) and AIR were inversely associated with type 2 diabetes (S (I), OR 0.53, 95% CI 0.39-0.73; AIR, OR 0.22, 95% CI 0.14-0.34 per SD; both p < 0.001), while both VAT and SAT were positively associated with type 2 diabetes (VAT, OR 1.68, 95% CI 1.22-2.33; SAT, OR 1.49, 95% CI 1.13-1.99; both p < 0.01). In a model including all four factors, S (I) and AIR (S (I), OR 0.55, 95% CI 0.37-0.80; AIR, OR 0.21, 95% CI 0.13-0.33; both p < 0.01) were significant predictors of type 2 diabetes, although associations with VAT and SAT were no longer significant. A significant sex x VAT interaction indicated a stronger association of VAT with type 2 diabetes in women than in men. CONCLUSIONS/INTERPRETATION: Insulin resistance, beta cell dysfunction and VAT predicted incident type 2 diabetes, with evidence of a stronger association of VAT with type 2 diabetes among women.

Erythema nodosum leprosum in Nepal: a retrospective study of clinical features and response to treatment with prednisolone or thalidomide.

INTRODUCTION: Erythema nodosum leprosum (ENL) is an inflammatory reaction, which may occur in the course of leprosy and may result in nerve function impairment and subsequent disability. METHODS: This retrospective study explores demographic and disease specific parameters. Severity of ENL was assessed using the Reaction Severity Scale (RSS). Records of 94 patients were reviewed. The study reports also on the treatment of 76 of these patients who were treated with prednisolone alone or thalidomide in addition to prednisolone. RESULTS Thirty percent of patients presented with ENL at time of diagnosis; 41% developed ENL-reaction in the first year of MDT. Forty-eight percent of patients were treated for ENL-reaction for less than 12 months; 13% for more than 5 years. High RSS-scores correlated with a longer duration of treatment. In group A (prednisolone) 51.7% and in group B (prednisolone and thalidomide) 76.6% of patients were male. Age, leprosy classification, delay of multidrug treatment (MDT) and interval between MDT and first ENL-symptoms did not differ significantly in both groups. Median duration of ENL-treatment was 15 months in group A versus 38 months in group B (P < 0.001). At the start of treatment, ENL-reaction was less severe in group A (RSS = 12) than in group B (RSS = 18; P = 0.003). DISCUSSION: ENL-symptoms may be of help in the early diagnosis and adequate treatment of ENL. Characterisation of (sub) groups of patients with ENL based on presence and severity of symptoms is important for future prospective studies to better evaluate the efficacy of interventions.

A biomechanical analysis of anterior load carriage.

Front load carriage is a common occupational task in some industries (e.g. agriculture, construction), but, as compared to lifting tasks, relatively little research has been conducted on the biomechanical loading during these activities. The focus of this study was to explore the low back biomechanics during these activities and, specifically, to examine the effects of load height and walking speed on trunk muscle activity and trunk posture. Eleven male participants participated in two separate front load-carriage experiments. The first experiment called for carrying a barbell (with weight corresponding to 20% of elbow flexion strength) at three heights (knuckle height, elbow height and shoulder height) at a constant horizontal distance from the spine. The second experiment called for participants to carry a bucket of potatoes weighing 14 kg at the same three heights, but with no further restrictions in technique. In both experiments, the participants performed this task while either standing still or walking at a self-selected speed. As they performed these tasks, the activity levels of the right-side muscle of the rectus abdominis, external oblique, biceps brachii, anterior deltoid and three levels (T9, T12 and L3) of the erector spinae were sampled. Mid-sagittal plane trunk posture was also quantified using three magnetic field-based motion sensors at T9, T12 and L3. The results showed a significant effect of both walking speed and load height on trunk posture and trunk muscle activity levels in both the barbell and bucket experiments. In the barbell experiment, the walking trials generated 43% more trunk muscle activity than the standing trials. Trials at shoulder height produced 11% more muscle activity than trials at elbow height in the T9 erector spinae muscles and 71% more muscle activity in the anterior deltoid. In the bucket experiment, trunk muscle activity responded in a similar fashion, but the key result here was the quantification of the natural hyperextension posture of the spine used to balance the bucket of potatoes. These results provide insight into muscle activation patterns in dynamic settings, especially (load) carrying biomechanics, and have implications in industrial settings that require workers to carry loads in front of their bodies.

Transformation of a leprosy hospital in Nepal into a rehabilitation centre: the Green Pastures Hospital experience.

Green Pastures Hospital for leprosy patients in Pokhara Nepal, was established in 1957 by the International Nepal Fellowship (INF) in a decade which saw the establishment of many similar hospitals in other leprosy endemic countries. In recent years, mainly due to significant improvements in leprosy control services and the wide implementation of multiple drug therapy (MDT) for all patients, many of these specialist hospitals have encountered 1) a decline in prevalence rate, 2) a large decline in the percentage of patients presenting with WHO grade 2 disability, 3) a decline in the previous indications for hospital admission, e.g. immunologically mediated reactions, and 4) a need to develop financial independence making them less dependent on donor agencies. In addition, the decision to change from specialist to general services opened up the possibility of using facilities and expertise for the rehabilitation of non-leprosy affected persons, whilst also moving towards the reduction of stigma and prejudice against patients with leprosy. This paper describes the process of 'transformation' of an established and well known leprosy hospital in Western Nepal from 1997 onwards into a general rehabilitation hospital. Careful preparation, with full involvement of existing staff and co-operation with other agencies in the hospital catchment area were key factors in what has now become a successful venture. Surgical procedures and orthopaedic appliance services for non-leprosy affected persons have increased in recent years and the introduction of a dermatology service has resulted in out-patient attendance rising from about 1000 in 1999 to 4500 in 2003. No evidence of reluctance to attend and use the facilities offered by this hospital because of stigma against leprosy has been encountered. Many of the changes described have been made in order to reduce financial dependence on donor sources of support, but the underlying reason for transformation is still based on the vision of the INF mission to work for and improve the condition of the marginalized in society.

Reliability of thumb web measurements.

Two new methods of thumb web space measurement, the intermetacarpal distance (IMD) and the derived intermetacarpal angle (DIMA), were proposed and compared with a conventional method for interrater reliability. Forty subjects (22 normal hands, 18 impaired hands) were measured. Reliability of the measurement was estimated using the intraclass correlation coefficient (ICC) and the Bland and Altman method of 95% limits of agreement. Overall, the IMD method showed an ICC of 0.88 with 95% limits of agreement of -6.9 to 5.6 mm (approximately +/-6.2 mm). Similarly, for the DIMA method, the ICC was 0.47 with 95% limits of agreement of -11.9 to 5.1 degrees (approximately +/-8.5 degrees ). The IMD method appears more reliable than the conventional method, which had an ICC of 0.26 and 95% limits of agreement of -17.5 to 9.2 degrees (approximately +/-13.3 degrees ). The IMD method is recommended as a reliable method of measuring the thumb web space.

Disruption of lactogenesis by retained placental fragments.

This case report describes a situation in which lack of milk production led the mother to seek help from a lactation consultant in private practice. Despite extensive breast stimulation with the baby at breast and mechanical breast expression, no milk was produced. Retained placenta was suspected by the lactation consultant. The mother was later diagnosed with placenta increta. Only when this condition was diagnosed and resolved did milk onset occur. It is important to evaluate for retained placental fragments when lactation appears to be delayed.

Functional significance of variation in bryophyte canopy structure.

In most bryophytes, the thickness of boundary layers (i.e., unstirred layers) that surrounds plant surfaces governs rates of water loss. Architectural features of canopies that influence boundary layer thickness affect the water balance of bryophytes. Using field samples (9.3 cm diameter cushions) from 12 populations (11 species) of mosses and liverworts, we evaluated the relationship between canopy structure and boundary layer properties. Canopy structure was characterized using a contact surface probe to measure canopy depth along perpendicular transects at spatial scales ranging from 0.8 to 30 mm on 186 points per sample. Semivariance in depth measurements at different spatial scales was used to estimate three architectural properties: surface roughness (L(r)), the scale of roughness elements (S(r)), and fine-scale surface texture, the latter characterized by the fractal dimension (D) of the canopy profile. Boundary layer properties were assessed by evaporation of ethanol from samples in a wind-tunnel at wind speeds from 0.6 to 4.2 m/s and applied to characterize mass transfer using principles of dynamic similarity (i.e., using dimensionless representations of conductance and flow). In addition, particle image velocimetry (PIV) was used to visualize and quantify flow over two species. All cushions exhibited the characteristics of turbulent as opposed to laminar boundary layers, and conductance increased with surface roughness. Bryophyte canopies with higher L(r) had greater conductances at all wind speeds. Particle image velocimetry analysis verified that roughness elements interacted with flow and caused turbulent eddies to enter canopies, enhancing evaporation. All three morphological features were significantly associated with evaporation. When L(r), S(r), and D were incorporated with a flow parameter into a conductance model using multiple linear regression, the model accounted for 91% of the variation in mass transfer.

Towards an understanding of non-compliance. An assessment of risk factors for defaulting from leprosy treatment.

Within the Eastern Leprosy Control Project of Nepal, a retrospective case control study looked for simple factors that might be used operationally to predict non-compliant behaviour in patients. Patients with these factors would then become the targets of measures such as intensified health education messages and home visits in order to reduce the risk of defaulting. A study of 1442 patient cards (half defaulters, half treatment completed) revealed occasional small but significant demographic and clinical differences, but none was of a sufficient magnitude to be operationally useful. Review of the attendance of patients in the first few months of treatment suggested that eventual defaulting was strongly associated with irregularity from the commencement of treatment. It is possible that an early indicator based on attendance over the first months can be used to target patients who are in danger of non-completion of treatment.

Echogenic intracardiac focus in 2nd-trimester fetuses with trisomy 21: usefulness as a US marker.

PURPOSE: To determine whether there is a relationship between the presence of an echogenic intracardiac focus in 2nd-trimester fetuses and trisomy 21 (Down syndrome). MATERIALS AND METHODS: A complete genetic ultrasonographic (US) scan was obtained in 3,303 consecutive fetuses with an estimated gestational age of 14.0-24.0 weeks (mean +/- SD, 17.1 weeks +/- 1.75). US was performed in a prospective fashion without any knowledge of karyotype and included assessment of any potential echogenic intracardiac focus (ie, calcified papillary muscle). Karyotypes were obtained in all fetuses. Maternal ages ranged from 13.0 to 47.4 years (mean, 35.1 years +/- 5.1). The prevalence of Down syndrome in this population was 1.6% (53 of 3,303 fetuses). RESULTS: An echogenic intracardiac focus was seen in 147 of the 3,192 karyotypically normal fetuses (4.6%) and 16 of the 53 fetuses with trisomy 21 (30%). The positive predictive value (PPV) of an echogenic intracardiac focus in this high-risk population was 9.8%; sensitivity, 30%; specificity, 95%; likelihood ratio, 6.6; and relative risk (RR), 8.2 (P <.001). For a sonographically isolated echogenic intracardiac focus, the PPV was 3.7%; sensitivity, 19%; specificity, 95%; likelihood ratio, 4.2; and RR, 4.8 (P =.002). CONCLUSION: A sonographically isolated echogenic intracardiac focus (no other anomalies or markers noted on a complete genetic sonogram) was associated in our high-risk population with a 4.8-fold (95% CI: 1.8, 12.5) increase in RR for trisomy 21 (P =.002).

Reliability of Semmes Weinstein monofilament and ballpoint sensory testing, and voluntary muscle testing in Bangladesh.

The reliability of methods of testing nerve function is important, since diagnostic decision making is a direct function of the quality of the test. Three methods of nerve function testing were investigated at the Danish Bangladesh Leprosy Mission (DBLM) in north Bangladesh, and assessed for inter-observer reliability. The three methods were 1) ballpoint pen test (BPT) for sensory function; 2) graded Semmes Weinstein monofilament test (SWM) for sensory function and 3) voluntary muscle testing (VMT) for motor function. The weighted kappa (kappa w) statistic was used to express inter-observer reliability. Using this statistic, 0 represents agreement no better than random, and 1.0 complete agreement. kappa w values of > or = 0.80 are reckoned to be adequate for monitoring and research. Fifty-three patients were tested, a Senior physiotechnician acting as 'gold standard' against whom four other staff physiotechnicians were assessed. All three testing methods were found to have minimal inter-observer variation, with the kappa w for inter-observer agreement using BPT being 0.86, the SWM 0.92, and VMT 0.94. It is concluded that in trained and experienced hands, all three methods are reliable and repeatable to a level allowing confident use of results obtained in monitoring and research.

A scale to assess activities of daily living in persons affected by leprosy.

The aim of this study was to develop a scale for identifying disability among people in the rural areas of developing countries. The studies were carried out in the Green Pastures Hospital and the leprosy field programme of the Western Region of Nepal. With the help of staff experienced in working with people with disability, a 68-question questionnaire was made, based on the International Classification of Impairments, Activities and Participation (ICIDH-2). A survey was carried out of 269 people affected by leprosy who had impairments, as well as a sample of those who were unimpaired. The survey results were used to develop the questionnaire into a scale, using standard scale development methods. This included checking of criterion validity, discrimination and reliability and stability using weighted kappa statistics. Of the 68 questions, 38 were included in the second draft of the instrument. Eight questions were added to identify difficulty in relationships, about the use of aids and about occupation and employment. The sum score of the scale against the expert score gave a Spearman correlation coefficient of 0.72. Intra- and inter-interviewer reliability coefficients were 0.77 (95% CI 0.73-0.81) and 0.61 (95% CI 0.56-0.67), respectively. The stability test gave an overall kappa of 0.76 (95% CI 0.70-0.82). Four questions with particularly poor results were omitted from the final draft of the instrument. An interview-based instrument was developed for identifying limitations in activities of daily living (disability) in people living in a rural setting in a developing country--the Green Pastures Activity Scale (GPAS). The scale performed well during validity and reliability testing. It consists of 34 activity questions, five relationship questions, and three questions on the use of aids, occupation and employment.

Substrate oxidation and availability during acute exercise in non-obese, obese, and post-obese sedentary females.

OBJECTIVE: This study compared fat oxidation rates during an acute bout of cycle ergometry exercise (E) typical of progressive fat oxidation in healthy, but sedentary, women of different obesity histories. DESIGN: Five never-obese (NO) (mean age=25+/-3 (s.e.)y, mean body fat=25.0+/-2.8 (s.e.)%), five obese (O) (26+/-3 y, 44. 4+/-1.7%), and five post-obese (PO) (22+/-1 y, 32.2+/-3.0%) women cycled for 60 min at 60-65% peak VO2. To identify the specific effects of E, a control trial consisting of 60 min of seated rest (R) was also performed. E and R trials were counterbalanced one month apart in the follicular phase and conducted following a 3 d normalized, eucaloric diet. MEASUREMENTS: Dual energy X-ray absorptiometry (DEXA) was used to determine body composition, and all were weight stable for at least eight weeks prior to experimentation. During both trials breath by breath measurements of VO2 and RER were used to determine substrate oxidation and energy expenditure. Blood samples were collected for hormone and metabolite analysis before, and every 15 min during exercise or rest. RESULTS: All three groups showed a similar and progressive shift toward fat oxidation as exercise progressed. No group differences were observed for E energy expenditure or fat oxidation. Glycerol (P<0.0001) and free fatty acids (P<0.0001) increased similarly in all three groups, but PO maintained the highest free fatty acid level during exercise (group effect; P<0.01). E and R decreased (P<0.001 for both) insulin levels across groups, with lowest levels noted in PO and highest in O. Plasma epinephrine (P<0.0001) and norepinephrine (P<0.001) increased similarly during E in all three groups. Plasma growth hormone (GH) levels rose (P<0.05) during E, with a pronounced increase observed in PO. CONCLUSION: We conclude that exercise of equal relative intensity elicited similar fat oxidation rates among NO, O, and PO women, despite group differences in free fatty acid availability. The PO women's persistently lower insulin and higher plasma GH levels may have enhanced free fatty acid availability.

Verbal retelling abilities in adolescents with and without language-learning disabilities for social studies lectures.

Verbal retelling abilities for social studies lectures were examined and compared in 20 adolescent boys, ages 12-5 to 14-7, with language-learning disabilities (LLD) and 29 with normal language abilities (NL). Participants viewed one videotaped social studies lecture with a comparison expository discourse structure and one with a causation discourse structure. Following each lecture presentation, participants verbally retold the lecture. Results of several repeated-measures analyses of variance indicated that the group with LLD produced a significantly smaller number of T-units, subordinate clauses, subordinate clauses per T-unit, T-units per second, lecture components per second, and percentage of lecture components in their retellings, compared with the group with NL, regardless of lecture type. Both groups produced a significantly greater number of T-units and subordinate clauses for the comparison lecture. By contrast, both groups recalled a significantly greater number of lecture components per T-unit and per second for the causation lecture. Results indicated that the comparison discourse structure facilitated more substantive and elaborate retellings, whereas the causation discourse structure facilitated more efficient, concise retellings in both groups. Research and instructional implications are discussed.