Modelling the performance of an integrated fixed-film activated sludge (IFAS) system: a systematic approach to automated calibration.

IFAS systems are inherently complex due to the hybrid use of both suspended and attached bacterial colonies for the purpose of pollutant degradation as part of wastewater treatment. This poses challenges when attempting to represent these systems mathematically due to the vast number of parameters involved. Besides becoming convoluted, large effort will be incurred during model calibration. This paper demonstrates a systematic approach to calibration of an IFAS process model that incorporates two sensitivity analyses to identify influential parameters and detect collinearity from a subset of 68 kinetic and stoichiometric parameters, and the use of the Nelder-Mead optimization algorithm to estimate the required values of these parameters. The model considers the removal of three critical pollutants including biochemical oxygen demand (BOD), total nitrogen (TN) and total suspended solids (TSS). Results from the sensitivity analyses identified four parameters that were the primary influence on the model. The model was found to be most sensitive to the two stoichiometric parameters including aerobic heterotrophic yield on soluble substrate whose total effects were responsible for 92.4% of the model's BOD output sensitivity and 92.8% of the model's TSS output sensitivity. The anoxic heterotrophic yield on soluble substrate was observed to be responsible for 54.3% of the model's TN output sensitivity. To a lesser extent the two kinetic parameters, aerobic heterotrophic decay rate and reduction factor for denitrification on nitrite, were responsible for only 8.0% and 13.1% of the model's BOD and TN output sensitivities respectively. Parameter estimation identified the need for only minor adjustments to default values in order to achieve sufficient accuracy of simulation with deviation from observed data to be only ± 3.6 mg/L, ± 1.3 mg/L, and ± 9.5 mg/L for BOD, TN and TSS respectively. Validation showed the model was limited in its capacity to predict system behaviour under extreme dissolved oxygen stress.

The meiotic recombination hotspots of Schizosaccharomyces pombe.

Meiotic recombination predominantly occurs at genomic loci referred to as recombination hotspots. The fission yeast, Schizosaccharomyces pombe, has proved to be an excellent model organism in which to study details of the molecular basis of meiotic recombination hotspot activation. S. pombe has a number of different classes of meiotic hotspots, indicating that a single pathway does not confer hotspot activity throughout the genome. The M26-related hotspots are a particularly well characterised group of hotspots and details of the molecular activation of M26-related hotspots are now coming to light. Moreover, genome-wide DNA array analysis has been applied to the question of meiotic recombination in this organism and we are now starting to get a picture of recombination hotspot distribution on a genome-wide scale.

Identification of a fibrinolytic enzyme in Schistosoma mansoni eggs and modulated blood fibrinogen metabolism in S. mansoni-infected mice.

Aqueous extracts of Schistosoma mansoni eggs have been shown to have fibrinolytic activity inhibitable by a serine protease inhibitor. Fibrinolytic activity was not present in extracts of either adult worms or cercariae. A 27 kDa enzyme that was proteolytically active on fibrinogen in zymography and that degraded fibrinogen in a pattern similar to that of plasmin, is presumed to be responsible for the schistosome egg fibrinolytic activity. Anti-human fibrinogen antisera were shown to have antibodies that cross-reacted with mouse fibrinogen in Western immunoblots. Electroblotted sera from S. mansoni-infected and control uninfected mice displayed different antigenic profiles when probed with the cross-reactive anti-human fibrinogen antibodies, suggesting an alteration in mouse host fibrinogen metabolism as a result of the parasitic infection. We discuss the possibility that modulation of fibrinogen metabolism is a factor in a recently discovered anti-atherogenic effect exerted by schistosomes.

Warfarin treatment of chronic idiopathic urticaria and angio-oedema.

BACKGROUND: Chronic idiopathic urticaria is a disabling condition that does not always respond to antihistamine drugs and other agents are sometimes needed to control disease activity. Warfarin has demonstrated efficacy in single unblinded case studies [1] but has been dismissed by others [2]. OBJECTIVE: We investigated the effect of warfarin treatment in eight patients with chronic idiopathic urticaria unresponsive to antihistamines in an open study. Six of the eight patients responded to treatment and three had a dramatic response. These three were included in a double-blind placebo-controlled trial of warfarin therapy to confirm significant benefit from treatment. METHODS: The three warfarin responders had their stable warfarin dose encapsulated and placebo capsules were provided. A double-blind placebo-controlled crossover trial was performed on each patient. Visual analogue scores recorded disease activity. RESULTS: Comparison of visual analogue scores showed a significant benefit while on warfarin with a reduction in pruritus and angio-oedema. CONCLUSION: This is the first double-blind placebo-controlled study to show a response of chronic idiopathic urticaria to warfarin. The mechanisms of action are unclear and require further study.

Chemoprophylaxis compliance in travelers with malaria.

Much effort and resources have been focused on improving or evolving antimalarial prophylactic regimens in order to reduce the increasing problems of malaria infection in nonimmune travelers to malaria endemic regions. Falciparum malaria in travelers returned from Africa has been attributed to reduced efficacy of chloroquine against chloroquine-resistant strains of Plasmodium falciparum (CRPF). Reported prophylaxis use by tourists from East Africa suggests only 52% admit taking their chemoprophylaxis without any missed doses. The effect of noncompliance with chloroquine (CQ) or proguanil (PG) in East Africa has been estimated as equivalent to taking no prophylaxis at all. The influence of poor compliance and/or parasite resistance on the changing pattern of malaria among travelers needs to be understood if methods of reducing morbidity are to be identified. In a number of studies, prophylaxis compliance in travelers has been collected by self-administered questionnaires from which prophylaxis efficacy of drug regimens has been calculated. The interpretation of drug efficacy has hinged on drug compliance and is controversial. We have addressed the role of chemoprophylaxis compliance in travelers with malaria using a prospective study of 368 malaria patients attending the Hospital for Tropical Diseases by examining their travel history and reported prophylaxis compliance compared to their actual plasma drug levels. This has enabled us to characterize the role of CRPF and poor compliance in the etiology of breakthrough malaria in travelers.

Lansoprazole, clarithromycin and metronidazole for seven days in Helicobacter pylori infection.

BACKGROUND: This study determines the efficacy and safety of a 1-week triple therapy regimen of lansoprazole, clarithromycin and metronidazole in an area with a high prevalence of pre-treatment metronidazole-resistant strains of Helicobacter pylori. METHODS: Seventy-five H. pylori positive patients with gastritis or duodenal ulcer were entered into an open study of lansoprazole 30 mg o.m., clarithromycin 250 mg b.d. and metronidazole 400 mg b.d. H. pylori status was determined by CLOtest, histology, culture and by 13C-urea breath test (repeated > or = 28 days after treatment). RESULTS: Seventy-one patients completed the treatment and returned for follow-up. H. pylori was eradicated in 61 of 71 (86%) patients by per-protocol analysis, and in 61 of 75 (81%) patients by intention-to-treat analysis. H. pylori was eradicated in 12 of 16 (75%) patients with metronidazole-resistant strains compared with 22 of 24 (92%) in patients with metronidazole-sensitive strains of H. pylori (P = 0.14). Fourty-five patients reported at least one adverse event, and three patients stopped treatment due to them (two with headaches and one with diarrhoea). CONCLUSIONS: A 1-week course of lansoprazole 30 mg o.m., clarithromycin 250 mg b.d. and metronidazole 400 mg b.d. eradicates H. pylori in up to 86% of patients. It is of proven benefit in patients with pre-treatment metronidazole-resistant strains of H. pylori.

'Sticky' neutrophils, pathergic arthritis, and response to heparin in pyoderma gangrenosum complicating ulcerative colitis.

Pyoderma gangrenosum is strongly associated with inflammatory bowel disease and exhibits pathergy, occurring at sites of previous minor trauma. A patient is presented with a 21 year history of extensive ulcerative colitis, who developed pyoderma gangrenosum and arthralgia while receiving high dose corticosteroids for active ulcerative colitis. The arthralgia exhibited pathergy affecting particularly the left temporomandibular joint, which was stressed by an asymmetric bite, and the left elbow, which had been fractured many years previously. This prompted the hypothesis that neutrophils in this condition may be marginated, as a result of increased stickiness of either the neutrophil or the vascular endothelium. The introduction of heparin therapy was associated with rapid resolution of the arthralgia, pyoderma gangrenosum, and ulcerative colitis.

Flow motion in peripheral diabetic neuropathy.

1. Flow motion is the cyclical variation in blood flow owing to the rhythmical opening and closing of arterioles. Previous studies have suggested that cutaneous flow motion may be altered in diabetic neuropathy but have not been consistent in their findings. 2. In order to assess the effect of diabetic peripheral neuropathy on flow motion, we have examined the frequency and amplitude of flow motion in 12 patients with diabetic peripheral neuropathy, 10 age-matched diabetic patients without peripheral neuropathy and 10 age-matched non-diabetic controls. 3. Peripheral neuropathy was diagnosed by a history of foot ulceration or chronic painful neuropathy, clinical examination and abnormal peroneal nerve conduction velocities. Blood flow, using laser Doppler flowmetry, was measured at four sites on the dorsum of both hands and feet. Flow motion was analysed using fast Fourier transform analysis, between 0.05 and 0.2 Hz, and displayed on a power spectral density graph. Predominant frequency and relative amplitude of flow motion were calculated. 4. Relative amplitude and frequency of flow motion were similar in the hands of all three groups, as was the frequency in the feet of the three groups. Relative amplitude was significantly smaller in the feet of diabetic patients with neuropathy (median 7.2%, 95% confidence interval 4.9-9.4%) than in diabetic patients without neuropathy (median 13.5%, 95% confidence interval 6.3-21.5%, P < 0.02) or in non-diabetic control subjects (median 10.3%, 95% confidence interval 6.9-27.4%, P < 0.02). 5. Flow motion amplitude is reduced in diabetic peripheral neuropathy. The control of flow motion amplitude appears to be at least partly under neurological control.

A family with pachyonychia congenita affecting the nails only.

A family with pachyonychia congenita in which affected individuals showed nail involvement only is described. Pachyonychia congenita is a rare hereditary disorder inherited in an autosomal dominant manner. Various classifications of pachyonychia congenita have been suggested but none indicates nail involvement as a solitary finding.

Traveller's diarrhoea; a controlled study of its effect on chloroquine and proguanil absorption.

The potential for traveller's diarrhoea to impair proguanil and chloroquine absorption and cause chemoprophylaxis failure was investigated in a study involving recently returned travellers who were either asymptomatic or presented with diarrhoea. A routine dose of chemoprophylaxis was administered to 12 travellers with diarrhoea and 12 asymptomatic subjects. The subjects undertook a lactulose-mannitol intestinal permeability test and were bled hourly after prophylaxis ingestion. Plasma analysis of chloroquine and proguanil from serial samples revealed a significantly lower proguanil Cmax (146 ng/mL vs. 196 ng/mL, P = 0.05), and longer tmax (3.1 h vs. 2.6 h, P = 0.05) in the diarrhoea cohorts. The absorption coefficient was lower for proguanil (0.57 vs. 0.76) but the difference did not quite reach levels of significance. Chloroquine kinetics were similar in both groups. The diarrhoea cohort had a three-fold higher lactulose absorption, influencing the mean lactulose mannitol:ratio, 0.114 +/- 0.17 compared to the control ratio of 0.02 +/- 0.01 (P = 0.04). Symptomatic subjects had impaired mucosal function which reduced the absorption of proguanil but not chloroquine, a phenomenon which may reduce prophylactic efficacy.

Hemodynamics of leg ulceration assessed by laser Doppler flowmetry.

BACKGROUND: Cutaneous blood flow and the venoarteriolar reflex can be assessed in the leg by laser Doppler flowmetry. OBJECTIVE: Our purpose was to compare these measurements in ulcerated and nonulcerated skin in venous and arterial disease and to determine whether either changes with healing. METHODS: Studies were performed in 20 patients with venous disease, 16 with arterial disease, and 12 control subjects and repeated sequentially in 15 patients with small venous ulcers until they healed. RESULTS: Blood flow in nonulcerated skin was greatest in venous disease (but not when severe ulceration was excluded). The reflex was exaggerated in nonulcerated skin in venous disease but attenuated in the base of both venous and arterial ulcers. The reflex reappeared in the base of the venous ulcers as they healed. CONCLUSION: Measurement of the venoarteriolar reflex in nonulcerated skin distinguished between venous and arterial disease and its reappearance in the base of venous ulcers was associated with healing.

Epidemic visceral leishmaniasis in Sudan: a randomized trial of aminosidine plus sodium stibogluconate versus sodium stibogluconate alone.

In a comparative trial of treatment in southern Sudan, visceral leishmaniasis was diagnosed by the following symptoms: fever for > 1 month, splenomegaly, and antileishmanial direct agglutination test (DAT) titer of > or = 1:25,600. Patients (200) were randomized to receive sodium stibogluconate (Sbv) at 20 mg/kg/day for 30 days (groups S, n = 99) or Sbv at 20 mg/kg/day plus aminosidine at 15 mg/kg/day for 17 days (group AS, n = 101). Of 192 patients who had spleens or lymph nodes aspirated at entry, 134 (70%) were positive for parasites. During treatment, 7% in group S and 4% in group AS died. All 184 patients who completed treatment were clinically cured. At days 15-17, microscopy of aspirates showed that 57 (95%) of 60 in group AS were negative for parasites compared with 47 (81%) of 58 in group S (P = .018). At day 30, 57 (93.4%) of 61 group S aspirates were negative.

Scalp cyst with heterotopic brain tissue.

A multilocular scalp lesion was noticed at birth in a female infant. There was no underlying skull defect. Histological examination revealed neural tissue staining with S-100 and GFAP, but not with a neurofilament stain, which is in keeping with a glial cell origin. Heterotopic brain tissue is a rare developmental abnormality, which usually has no effect on neurological development. It should be considered in the differential diagnosis of scalp lesions in neonates.

The changing pattern of imported malaria in British visitors to Kenya 1987-1990.

Following a sudden increase of imported malaria from Kenya in December 1989-January 1990, an investigation was set up to identify risk factors for travellers' malaria. A questionnaire asking for details of travel patterns and compliance with prophylaxis was sent to cases reported over the 6-month Kenyan winter period. Quarterly malaria attack rates between January 1987 and June 1991 were calculated and linked to meteorological conditions in Mombasa. The number of travellers to Kenya has doubled in the 4 years studied and the quarterly rates varied 4-fold over this period. There was no clear seasonal pattern of malaria in travellers, nor was there any clear relation of malaria to coastal rainfall. Compliance with chemoprophylaxis was poor, with only 16% of cases using currently advised regimens. While the annual malaria attack rate per 10,000 travellers decreased by 37% over the study period, the total numbers of malaria cases imported from Kenya rose by 61%, reflecting the increase in the numbers of travellers to the region. As the popularity of East Africa as a tourist destination continues to increase, Kenya will remain an important and significant source of malaria imported into the UK.

Inflammatory ringworm with unusual features.

Zoophilic dermatophyte infections are often inflammatory but severe widespread inflammatory lesions of glabrous skin, as in the female patient described, are unusual. Most cases of M. canis ringworm can be traced to an infected animal. This dermatophyte is associated with a variety of clinical presentations on glabrous skin and is being isolated with increasing frequency in some countries.