East Africa's pastoralist emergency: is climate change the straw that breaks the camel's back?

The global warming trend of climate change is having severe adverse effects on the livelihoods of the Turkana pastoralists of northwestern Kenya. Care has to be taken in making assertions about the impact of climate change. The biggest effects may come not from lower average rainfall but from a widening of the standard deviation as weather extremes become more frequent. In a region already prone to drought, disease and conflict, climate change, access to modern weapons and new viral livestock diseases are now overwhelming pastoralists' coping capacity and deepening the region's roughly 30-year dependency on famine relief. This article examines the livelihood strategies of the Turkana and several poverty reduction programmes currently established, while addressing the reality that traditional pastoralism may no longer be a viable livelihood option, given the effects of climate change, disease and the ensuing conflict over diminishing resources. The findings conclude that the future for traditional Turkana pastoralists is dismal because they continue to depend on an environment that may no longer support them. Humanitarians are recommended to shift their focus to advocate and invest in alternative livelihood strategies that generate economic independence and help the Turkana adapt to their changing environment.

Veterinary medicines in the environment.

The impact of veterinary medicines on the environment will depend on a number of factors including physicochemical properties, amount used and method of administration, treatment type and dose, animal husbandry practices, manure storage and handling practices, metabolism within the animal, and degradation rates in manure and slurry. Once released to the environment, other factors such as soil type, climate, and ecotoxicity also determine the environmental impact of the compound. The importance of individual routes into the environment for different types of veterinary medicines varies according to the type of treatment and livestock category. Treatments used in aquaculture have a high potential to reach the aquatic environment. The main routes of entry to the terrestrial environment are from the use of veterinary medicines in intensively reared livestock, via the application of slurry and manure to land, and by the use of veterinary medicines in pasture-reared animals where pharmaceutical residues are excreted directly into the environment. Veterinary medicines applied to land via spreading of slurry may also enter the aquatic environment indirectly via surface runoff or leaching to groundwater. It is likely that topical treatments have greater potential to be released to the environment than treatments administered orally or by injection. Inputs from the manufacturing process, companion animal treatments, and disposal are likely to be minimal in comparison. Monitoring studies demonstrate that veterinary medicines do enter the environment, with sheep dip chemicals, antibiotics, sealice treatments, and anthelmintics being measured in soils, groundwater, surface waters, sediment, or biota. Maximum concentrations vary across chemical classes, with very high concentrations being reported for the sheep dip chemicals. The degree to which veterinary medicines may adsorb to particulates varies widely. Partition coefficients (K(d)) range from low (0.61 L kg(-1)) to high (6000 L kg(-1)). The variation in partitioning for many of the compounds in different soils was significant (up to a factor of 30), but these differences could be not be explained by normalization to the organic carbon content of the soils. Thus, to arrive at a realistic assessment of the availability of veterinary medicines for transport through the soil and uptake into soil organisms, the K(oc) (which is used in many of the exposure models) may not be an appropriate measure. Transport of particle-associated substances from soil to surface waters has also been demonstrated. Veterinary medicines can persist in soils for days to years, and half-lives are influenced by a range of factors including temperature, pH, and the presence of manure. The persistence of major groups of veterinary medicines in soil, manure, slurry, and water varies across and within classes. Ecotoxicity data were available for a wide range of veterinary medicines. The acute and chronic effects of avermectins and sheep dip chemicals on aquatic organisms are well documented, and these substances are known to be toxic to many organisms at low concentrations (ng L(-1) to microg L(-1)). Concerns have also been raised about the possibility of indirect effects of these substances on predatory species (e.g., birds and bats). Data for other groups indicate that toxicity values are generally in the mg L(-1) range. For the antibiotics, toxicity is greater for certain species of algae and marine bacteria. Generally, toxicity values for antibacterial agents were significantly higher than reported environmental concentrations. However, because of a lack of appropriate toxicity data, it is difficult to assess the environmental significance of these observations with regard to subtle long-term effects.

Autoantibodies to human tissue transglutaminase: superior predictors of coeliac disease.

BACKGROUND: Using selected sample populations, we compared sensitivity and specificity of autoantibodies to guinea pig and human tissue transglutaminase to assess if the human antigen is superior for predicting coeliac disease. METHODS: Four commercial enzyme-linked immunoassay kits using human tissue transglutaminase as antigen were used to measure autoantibody levels in serum samples from untreated adult coeliacs (n = 32). They were from a series of 130 cases diagnosed between 1997 and 1999 and chosen to bias the group towards subjects with negative autoantibodies when measured with guinea pig tissue transglutaminase as antigen. Samples from 38 control subjects (biased towards false-positive levels with guinea pig antigen) were used to compare specificity. We also assessed if human antigen kits could differentiate between levels in normal subjects and in selective IgA deficiency. RESULTS: Sensitivity for coeliac disease in this selected group using the human antigen kits ranged from 88% to 100%. Three kits showed significantly higher specificity (82%-97%, P < 0.05) than the guinea pig antigen kit (71%) for the samples studied. No kit achieved complete separation between normal autoantibody levels and lower levels in selective IgA deficiency. CONCLUSIONS: All human antigen kits showed significantly higher sensitivity for coeliac disease compared to guinea pig antigen (P < 0.001). Receiver operating characteristic curves confirmed the superior diagnostic accuracy of the human antigen kits.

Alendronate in the treatment of primary hyperparathyroid-related osteoporosis: a 2-year study.

We investigated the effect of alendronate on calcium, PTH, and bone mineral density in 27 female and 5 male patients with primary hyperparathyroidism. The treatment group [n = 14; T score < or = -2.5 SD at the femoral neck (FN) or T < or = -1.0 SD plus previous nonvertebral fracture] was given alendronate 10 mg/d for 24 months. The second group (n = 18; T score > -2.5 SD at the FN) was untreated. Biochemistry was repeated at 1.5, 3, 6, 12, 18, and 24 months, and dual-energy x-ray absorptiometry at 12 and 24 months. There were no significant between-group baseline differences in calcium, creatinine, or PTH. Alendronate-treated patients gained bone at all sites [lumbar spine (LS), 1 yr gain, +7.3 +/- 1.7%; P < 0.001; 2 yr, +7.3 +/- 3.1%; P = 0.04). Untreated patients gained bone at the LS over 2 yr (+4.0 +/- 1.8%; P = 0.03) but lost bone elsewhere. Calcium fell nonsignificantly in the alendronate group between baseline (2.84 +/- 0.12 mmol/liter) and 6 wk (2.76 +/- 0.09 mmol/liter), with a nonsignificant rise in PTH (baseline, 103.5 +/- 14.6 ng/liter; 6 wk, 116.7 +/- 15.6 ng/liter). By 3 months, values had reverted to baseline. In primary hyperparathyroidism, alendronate is well tolerated and significantly improves bone mineral density at the LS (with lesser gains at FN and radius), especially within the first year of treatment. Short-term changes in calcium and PTH resolve by 3 months.

Impact of landmark reliability on the planar Procrustes analysis of tooth shape.

In a recent study, the ideas of Procrustes analysis were introduced to the study of tooth shape for teeth represented as configurations of 'landmarks' from digital images. This study aimed to establish how well the method could be expected to perform (in its standard form) when used on surfaces from a variety of tooth types and, in particular, how much impact inconsistencies in the positioning of landmarks would have on investigations of shape. Using four different operators' images and landmarks from 10 different surfaces from each of 20 patients, the consequences of location inconsistency are evaluated by calculating its effect on the recorded variation in Procrustes fits, obtained for each set of multiple representations. The proportion of variation in shape attributable to actual differences between patients, rather than other sources of error, ranged from only 36 to 65% for the five buccal-surfaces considered and was no more than 30% for any of the five occlusal surfaces. Further examination of these results indicated that consistent orientation differences before imaging might be a particular source of error in obtaining any occlusal-landmark data, as might location ambiguities around the edges of the teeth. Orientation effects were also suggested for the buccal-surfaces of the molar teeth. In contrast, the relatively flatter buccal-surfaces of the incisors and canines produced the most reliable data. Methods of analysis need to accommodate these problems if landmark data are to be used to describe variations in tooth shape. Different surfaces each present their own particular difficulties and so a variety of solutions may be required.

Group formation games with reappraisal.

The formation of a social group, such as the group of individuals sharing a territory, depends on the interaction between choices made by individuals to stay or disperse. The process can be modelled as a multi-player variant of the well-known War of Attrition in evolutionary game theory, as shown by Blackwell (1997; J. Theor. Biol.189, 175-181). In this paper, we extend the set of strategies defined there by allowing reappraisal during the game. We give a formal analysis of the evolutionarily stable strategy, where one exists, and illustrate it with an example based on badger (Meles meles) territoriality. The results predict that group size will be well adapted to, and very sensitive to, the precise conditions under which the game is played, and give an indication of the potential for parent-offspring conflict.

Bayesian inference for a random tessellation process.

This article describes an inhomogeneous Poisson point process in the plane with an intensity function based on a Dirichlet tessellation process and a method for using observations on the point process to make fully Bayesian inferences about the underlying tessellation. The method is implemented using a Markov chain Monte Carlo approach. An application to modeling the territories of clans of badgers, Meles meles, is described.

Planar Procrustes analysis of tooth shape.

Accurate quantification of variation in tooth shape is important in studies of dental development, which typically have involved measuring distances between subjectively identified landmarks, key points of correspondence on teeth. An established statistical framework now exists for the analysis of shape when objects are represented as configurations of landmark coordinates; allowing work with the full geometry of objects, which is otherwise lost. This approach was introduced here to the study of tooth morphology, demonstrating how after optimally matching shapes to account for the unwanted effects of location, scale and rotation, most standard descriptive and inferential statistical techniques can be adapted and applied successfully. The techniques are illustrated using a sample of buccal-surface images of central incisors from patients with hypodontia; a significant difference is found in mean buccal-surface shape (Hotelling's two-sample T(2)-test; P=0.004) when compared to a corresponding control group. Successful implementation of these methods depends on the accuracy and reliability with which the landmarks are collected; issues and problems to be addressed are discussed.

A comparison of continuous alendronate, cyclical alendronate and cyclical etidronate with calcitriol in the treatment of postmenopausal vertebral osteoporosis: a randomized controlled trial.

A number of drugs are now available for the treatment of established osteoporosis and have been shown to significantly increase bone mineral density (BMD). There are, however, few comparative treatment studies and, furthermore, adverse events remain a problem with some of the newer agents, particularly in the elderly, in everyday clinical practice. We report a 12 month, open labeled, randomized controlled, prospective treatment study in 140 postmenopausal women with established vertebral osteoporosis, comparing the effect of continuous alendronate, cyclical alendronate and cyclical etidronate with calcitriol in terms of gain in BMD, reduction in bone turnover markers and adverse event profile. The mean percentage increases in BMD at 12 months, at the spine and hip respectively, were: continuous alendronate 5.7%, 2.6%; cyclical alendronate 4.1%, 1.6%; cyclical etidronate 4.9%, 2.0% (p<0.0 1) and calcitriol 2.0%, 0.4% (NS). In comparison with calcitriol, the mean changes in BMD at the spine and hip respectively were greater in the other groups; continuous alendronate: 3.7% (95% CI 1.4 to 8.3), 2.2% (95% CI 0.7 to 4.0); cyclical alendronate: 2.1% (95% CI 1.2 to 6.4), 1.2% (95% CI -0.3 to 3.0); cyclical etidronate: 2.9% (95% CI 1.9 to 6.5), 1.6% (95% CI 0.9 to 3.1)). The reduction in bone turnover markers was between 26% and 32% in the alendronate and etidronate groups (p<0.01), with a trend toward greater reduction in the continuous alendronate group. Eight patients discontinued the study: 6 in the continuous alendronate group, 1 in the cyclical alendronate group and 1 in the calcitriol group. Two patients in the cyclical etidronate group were unable to tolerate the Cacit component, but continued on substituting Cacit with Calcichew. In summary, 12 months of treatment with continuous alendronate, cyclical alendronate and cyclical etidronate are effective in terms of the gain in BMD at the anteroposterior spine and total hip in a comparable treatment population. These treatments are more effective than calcitriol and were generally well tolerated. Continuous alendronate showed a trend toward a larger gain in BMD and greater suppression of bone turnover markers than the other treatment groups, but had a higher incidence of adverse events, particularly within the older subgroup. Cyclical alendronate offers a lower adverse event profile and appears to be effective in comparison with continuous treatment, and may possibly be an alternative in the elderly. However, further studies are necessary, but more importantly with fracture end-points.

Cross-sectional analysis of renal transplantation osteoporosis.

We report a cross-sectional study of 54 adult female renal transplant recipients. We measured bone mineral density (BMD) of the lumbar spine, femoral neck, total hip, and mid- and total radius, and 38 patients underwent transiliac crest bone biopsy. Osteopenia was widespread with 31/54 (57%) of patients osteoporotic at one or more sites. Seventeen out of 54 (32%) of the patients had a prevalent low-trauma fracture. There was a clear trend in BMD reduction across spine, hip and midradius, with the predominantly cortical midradial site showing the greatest loss. We found no relationship between BMD and body mass index, parathyroid hormone (PTH), dose of immunosuppressant, years since transplantation, age at menopause, or years since menopause. Histologically, abnormal biopsies could be classified into three categories: hyperparathyroid (n = 20), adynamic (n = 14), and osteomalacic (n = 2). Mean PTH was lower (p = NS) and mean cumulative prednisolone dose was higher (p = 0.04) in the adynamic group compared with the hyperparathyroid group, but because of overlap between groups neither was an effective discriminator of histology. We suggest that bone biopsy is indicated in these patients to direct appropriate treatment. At the cellular level, there were significant negative correlations between osteoclast function (eroded surface, r = 0.47, p = 0.003) and osteoblast numbers (osteoblast surface, r = -0.40, p = 0.01) and cumulative exposure to prednisolone. We postulate that suppression of osteoblast function by prednisolone with unopposed bone resorption may result in relative hypercalcaemia and low PTH. This progressive reduction in bone turnover may promote or prolong the adynamic state.

The importance of CD34+/CD33- cells in platelet engraftment after intensive therapy for cancer patients given peripheral blood stem cell rescue.

The study was designed to determine whether the number of CD34+/CD33- cells given at autologous peripheral blood stem cell (PBSC) rescue after intensive therapy for cancer was a better predictor of platelet engraftment than the total number of CD34+ cells infused. Comparison between the total number of CD34+ cells/kg infused with the number of CD34+/CD33- cells/kg infused showed that, generally, 2 x 10(6) total CD34+ cells contained 1.38 x 10(6) CD34+/CD33- cells. There was poor correlation between the number of CD34+/CD33- and CD34+/CD33+ cells in the graft (r = 0.332). Engraftment times for platelets and neutrophils were evaluated in 68 patients. There was no significant difference between the times for platelets to reach >25 x 10(9)/l or neutrophils to reach >0.5 x 10(9)/l among patients who received > or <2 x 10(6) total CD34+ cells or > or <1.38 x 10(6) CD34+/CD33- cells although the latter was consistently the better predictor. Platelet recovery to >50 x 10(9)/l and >100 x 10(9)/l was delayed significantly in patients who received <1.38 x 10(6) CD34+/CD33-/kg infused (P < 0.02 and P < 0.05, respectively). The number of CD34+/CD33- cells/kg infused was a stronger predictor of platelet recovery than the total number of CD34+ cells infused (P < 0.05 for platelets >50 or >100 x 10(9)/l). Although platelet recovery was delayed significantly in patients who had <4 x 10(4) granulocyte-macrophage colony-forming units (CFU-GM)/kg infused, the time delay between receipt of PBSCs and availability of the colony counts limits the use of this assay to patients who do not require stem cells to be given immediately. Our data suggest that the number of CD34+/CD33- cells given at PBSC rescue provide information about the quality of the graft necessary for long-term platelet engraftment. However, since the percentage of CD34+/CD33- cells shows considerable inter-patient variation, measurement of this cell population may be important in patients who experience poor stem cell mobilization or when a target dose of 2 x 10(6) total CD34+ cells/kg is not achieved.

Absence of neurodegeneration and neural injury in the cerebral cortex in a sample of elderly patients with schizophrenia.

BACKGROUND: The cognitive and functional deterioration that is observed in many "poor-outcome" patients with schizophrenia suggests a neurodegenerative process extending into late life. Previous diagnostic studies have excluded known neurodegenerative diseases as explanations for this dementia. However, we hypothesized that relatively small accumulations of age- or disease-related neurodegenerative lesions occurring in an otherwise abnormal brain could result in deterioration in schizophrenia. METHODS: Postmortem studies were conducted using 23 prospectively accrued elderly persons with chronic schizophrenia for whom clinical ratings had been determined before death, 14 elderly control patients with no neuropsychiatric disease, and 10 control patients with Alzheimer disease. Immunohistochemistry and unbiased stereological counting methods were used to quantify common neurodegenerative lesions (ie, neurofibrillary tangles, amyloid plaques, and Lewy bodies) and cellular reactions to a variety of noxious stimuli (ubiquitinated dystrophic neurites, astrocytosis, and microglial infiltrates) in the ventromedial temporal lobe and the frontal and the calcarine (primary visual) cortices. RESULTS: No statistically significant differences were found between the patients with schizophrenia and the control patients without neuropsychiatric disease for the densities of any of the markers, while both groups exhibited fewer lesions than did the control group with Alzheimer disease. Correlation analyses in the schizophrenia sample failed to identify significant correlations between cognitive and psychiatric ratings and densities of any of the neuropathologic markers. CONCLUSIONS: No significant evidence of neurodegeneration or ongoing neural injury in the cerebral cortex was found in this sample of elderly persons with schizophrenia. Furthermore, the behavioral and cognitive deterioration observed in late life did not correlate with age-related degenerative phenomena.

The n-player war of attrition and territorial groups.

The choices made by juveniles, in territorial species, between dispersing and remaining in the natal territory, can be modelled as a simple multi-player evolutionary game, related to the well-known War of Attrition [Maynard Smith, J. (1974) J. theor. Biol. 47, 209-221; Haigh J. & Cannings, C. (1989) Acta Applicandae Mathematicae 14, 59-74]. The game is shown to have a unique evolutionarily stable strategy, involving a random choice between dispersing early in the game and staying indefinitely. An example is given, involving badgers (Meles meles), in which the key factor affecting the pay-off in the game is the possibility of inheriting the territory on the death of the current holders. The example indicates the sensitivity of the size of the group occupying the territory to the mortality rate among dispersers.

Prospective clinicopathologic studies of schizophrenia: accrual and assessment of patients.

OBJECTIVE: The purpose of this study was to characterize the neuropsychiatric profile of elderly patients with schizophrenia and establish a patient registry for prospective ante-mortem and post-mortem studies. METHOD: Medical records of all chronically institutionalized patients in eight state hospitals who were over the age of 65 and had a chart diagnosis of schizophrenia (N = 528) were reviewed. Of the potential subjects, 192 were excluded because of clinical histories inconsistent with a diagnosis of schizophrenia, 56 because of insufficient information to establish a psychiatric diagnosis, and 122 because of family members' refusal to give consent for autopsy in the event of death. To date, 81 of the remaining 158 patients have undergone neuropsychiatric evaluation with standard assessment instruments. RESULTS: Mini-Mental State scores of the 81 patients indicated severe dementia, and Functional Assessment Scale scores showed that patients required assistance with activities of daily living. All patients were rated as severely ill on the Brief Psychiatric Rating Scale. Ratings on the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms indicated a predominance of negative symptoms over positive. Of 30 patients who have died to date, research autopsies have been conducted on 26. CONCLUSIONS: Establishing a well characterized, prospective patient registry for clinicopathologic studies of schizophrenia is feasible but labor intensive. Diagnosis of schizophrenia with a high degree of confidence can be achieved by means of detailed chart review and assessment of current neuropsychiatric functioning with standard rating instruments. These data provide a basis for correlations of clinicopathologic factors.

The measurement of human endometrial prostaglandin production. A comparison of two in vitro methods.

Two in vitro methods for measuring human endometrial prostaglandin production were compared. Endometrial samples from eight patients were incubated over eight hours by a perifusion and a superfusion technique. The collected fractions were assayed by radioimmunoassay for PGE2 and PGF2 alpha. There was no significant difference between the perifusion and superfusion methods for the pattern and amount of PGE2 and PGF2 alpha production with time. Significantly higher production levels of PGE2 and PGF2 alpha were found in secretory phase endometria than in proliferative phase endometria. Histological examination of the tissue specimens by light and electron microscopy showed that both methods caused gross tissue damage after eight hours experimentation. The superfusion method produced more morphological damage than the perifusion method. However, no tissue damage could be detected after one hour of incubation with either method. Over an eight hour period neither the perifusion nor the superfusion technique appears to be a good indicator of in vivo endometrial prostaglandin production. Either technique used for only one to two hours may better reflect the in vivo situation.