Applications of Artificial Neural Networks in integrated water management: fiction or future?

An Artificial Neural Network (ANN) is nowadays recognized as a very promising tool for relating input data to output data. It is said that the possibilities of artificial neural networks are unlimited. Here we focus on the potential role of neural networks in integrated water management. An Artificial Neural Network (ANN) is a mathematical methodology which describes relations between cause (input data) and effects (output data) irrespective of the process laying behind and without the need for making assumptions considering the nature of the relations. The applications are widespread and vary from optimization of measuring networks, operational water management, prediction of drinking water consumption, on-line steering of wastewater treatment plants and sewage systems, up to more specific applications such as establishing a relationship between the observed erosion of groyne field sediments and the characteristics of passing vessels on the river Rhine. Especially where processes are complex, neural networks can open new possibilities for understanding and modelling these kinds of complex processes. Besides explaining the method of ANN this paper shows different applications. Three examples have been worked out in more detail. An intelligent monitoring system is shown for the on-line prediction of water consumption, ANN are successfully used for sludge cost monitoring and optimizing wastewater treatment and the usage of ANN is shown in optimizing and monitoring water quality measuring networks. An ANN appears to be a multiuse and powerful tool for modelling complex processes.

Chemotherapy affects the pattern of failure after shear loading of the proximal tibial growth plate.

INTRODUCTION: Tibial bones are shorter and less resistant to shear forces after treatment with doxorubicin, methotrexate, or cisplatin. We investigated the pattern of failure after shear loading of the proximal tibial growth plate in rats treated with these chemotherapeutic agents. MATERIALS AND METHODS: Male Wistar rats from the age of 4 weeks were given doxorubicin intravenously at 15 mg/m2 body surface area (BSA), methotrexate 60 mg/m2 BSA, or cisplatin 7.5 mg/m2 BSA. There was one nontreated control group fed ad libitum an d a diet control group for each drug-treated group. At the age of 13 weeks the tibial bones were dissected. The proximal growth plate was shear loaded to failure in the posteroanterior direction. The pattern of failure through the growth plate was examined. RESULTS: In rats fed ad libitum the failure pattern ran mainly through the transitional zone between proliferating and hypertrophic chondrocytes, but the pattern of failure showed considerable variability. The pattern in rats treated with methotrexate or cisplatin and that in their diet controls were comparable. In rats treated with doxorubicin the fracture ran mainly through the trabecular zone. CONCLUSIONS: Doxorubicin affects the pattern of failure after shear loading of the proximal tibial growth plate, but methotrexate and cisplatin do not. Special attention should be paid to epiphyseal injuries in children treated with doxorubicin.

The effect of chemotherapy on the morphology of the growth plate and metaphysis of the growing skeleton.

AIM: To establish the effect of three single chemotherapeutic agents on the growing skeleton, male Wistar rats were studied. METHODS: From the age of 4 weeks the rats were given iv doxorubicin (DOX) 15 mg/m(2) body surface area (BSA), methotrexate (MTX) 60 mg/m(2) BSA or cisplatin (CDDP) 7.5 mg/m(2) BSA. One non-treated control group was fed ad libitum (ad lib) and for every drug-treated group there was a diet-control group. After dissection at 13 weeks of age, morphology of the proximal tibial growth plate and metaphysis were studied. RESULTS: Compared to the ad lib group, DOX significantly decreased and MTX increased growth plate height (P<0.05). CDDP decreased height of the proliferating layer (P<0.05). Trabecular volume was decreased in the DOX and CDDP treated rats compared to the ad lib group (P=0.054). Compared to the diet control group trabecular bone volume was unaffected in the DOX group and decreased in the MTX and CDDP group (P<0.05). CONCLUSIONS: Doxorubicin causes growth plate thinning, methotrexate increases growth plate height and cisplatin does not affect growth plate height. All three chemotherapeutic agents decrease the trabecular volume of the proximal tibial metaphysis. Part of the effect of DOX, MTX and CDDP is related to the treatment induced malnutrition.

The effect of chemotherapy on the growing skeleton.

With the increasing use of high dose (poly)chemotherapy schedules in the treatment of childhood cancer it is particularly important to know the adverse effects of these treatments. Growth is a complex mechanism affected not only by chemotherapy but also by the malignancy itself as well as nutritional status, the use of corticosteroids and (cranial) radiation. In vitro and animal studies are often the most useful in determining the effect of a single chemotherapeutic agent on the growing skeleton. In vitro studies have shown doxorubicin, actinomycin D and cisplatin to have a direct effect on growth plate chondrocytes that in animals results in decreased growth and final height. Clinical studies with multiagent chemotherapy have demonstrated that antimetabolites decrease bone growth and final height. Childhood cancer survivors are at risk of a reduced bone mineral density, mainly due to methotrexate, ifosfamide and corticosteroids. This reduced bone mineral density persists into adult life and may increase bone fracture risk at an older age.

Selective inhibition of the Na+/H+ exchanger type 3 activates CO2/H+-sensitive medullary neurones.

Hypercapnia as well as lowered intracellular pH (pHi) increase the bioelectric activity of CO2/H+-sensitive neurones (VLNcs) of the ventrolateral medulla oblongata. Here we describe that immunoreactive Na+/H+ exchanger (NHE3) is present in ventrolateral neurones from medullary organotypic cultures (obex level). To test whether VLNcs can be acidified and thereby activated by inhibition of NHE3, we used the novel high-affinity NHE3-inhibitors S1611 and S3226. Both drugs raised the firing rates of VLNcs to at least 150% of the control values, and depolarized membrane potential by up to 15 mV at concentrations (0.5-1 micromol/l) suitable for selective inhibition of NHE3. The changes in bioelectric activity strongly resembled the responses to hypercapnia (PCO2: 60-100 mmHg). In BCECF-AM-loaded cultures a subfraction of ventrolateral VLNcs was found to be intracellularly acidified by 0.05-0.1 pH units following treatment with S1611; the time course of this acidification was similar to that evoked by hypercapnia. All drug effects were sustained and readily reversible upon washing. Non-CO2/H+-responsive medullary neurones as well as hippocampal CA3 neurones were unaffected by up to 20 micromol/l S1611. It is concluded that the selective inhibition of NHE3 acidifies and activates CO2/H+-sensitive neurones within the ventrolateral medulla oblongata.

S3226, a novel inhibitor of Na+/H+ exchanger subtype 3 in various cell types.

Inhibition of Na+/H+ exchange (NHE) subtypes has been investigated in a study of the mouse fibroblast L cell line (LAP1) transfected with human (h) NHE1, rabbit (rb) NHE2, rat (rt) or human (h) NHE3 as well as an opossum kidney cell line (OK) and porcine renal brush-border membrane vesicles (BBMV). S3226 ¿3-[2-(3-guanidino-2-methyl-3-oxo-propenyl)-5-methyl-phenyl]-N-isopro pylidene-2-methyl-acrylamide dihydro-chloride¿ was the most potent and specific NHE3 inhibitor with an IC50 value of 0.02 micromol/l for the human isoform, whereas its IC50 value for hNHE1 and rbNHE2 was 3.6 and approximately = 80 micromol/l, respectively. In contrast, amiloride is a weak NHE3 inhibitor (IC50>100 micromol/l) with a higher affinity to hNHE1 and rbNHE2. Cariporide (4-isopropyl-3-methylsulphonyl-benzoyl-guanidine methane-sulphonate), which has an IC50 for NHE3 of approximately 1 mmol/l, is a highly selective NHE1 inhibitor (0.08 micromol/l). Therefore, S3226 is a novel tool with which to investigate the physiological and pathophysiological roles of NHE3 in animal models.

Meniscal tissue regeneration in porous 50/50 copoly(L-lactide/epsilon-caprolactone) implants.

Porous materials of a high-molecular-weight 50/50 copolymer of L-lactide and epsilon-caprolactone with different compression moduli were used for meniscal repair. In contrast to the previously used 4,4'-diphenylmethane and 1,4-trans-cyclohexane diisocyanates containing polyurethanes, degradation products of the copolymer are non-toxic. Two series of porous materials with compression moduli of 40 and 100 kPa respectively were implanted in the knees of dogs using a new, less traumatizing suturing technique. A porous aliphatic polyurethane series with compression modulus of 150 kPa was implanted for comparison. Adhesion of the implant to meniscal tissue was found to be essential for healing of the longitudinal lesion. Copolymer implants showed better adhesion, probably due to the higher degradation rate of the copolymer. Fibrocartilage formation was found to be affected by the compression modulus of the implant. Implants with a modulus of 40 kPa did not show ingrowth of fibrocartilage, whereas implants with compression moduli of 100 and 150 kPa yielded 50-70 and 80-100% fibrocartilage respectively. During degradation the copolymer phase separated into a crystalline phase containing mainly L-lactide and an amorphous phase containing mainly epsilon-caprolactone. The copolymer degraded through bulk degradation.

Synthesis of the highly selective Na+/H+ exchange inhibitors cariporide mesilate and (3-methanesulfonyl-4-piperidino-benzoyl) guanidine methanesulfonate.

The syntheses of cariporide mesilate ((4-isopropyl-3-methanesulfonyl-benzoyl) guanidine methanesulfonate, HOE 642, CAS 159138-81-5), currently being clinically investigated as a protective drug in cardiac ischemia and reperfusion states, and of HOE 694 ((3-methanesulfonyl-4-piperidino-benzoyl)guanidine methanesulfonate, CAS 149725-40-6), widely used as a physiological and pharmacological research tool in studies comprising Na+/H+ exchange (NHE) inhibition, are described. Additionally, their selectivity on the different subtypes is disclosed.

Meniscal repair by fibrocartilage in the dog: characterization of the repair tissue and the role of vascularity.

Lesions in the avascular part of 20 canine menisci were repaired by implantation of a porous polyurethane. Seven menisci were not repaired and served as controls. The repair tissue was characterized by biochemical and immunological analysis. The role of vascularity in healing was studied by perfusion of menisci with Indian ink. Histologically, repair tissue inside the implants initially consisted of fibrous tissue containing type I collagen. After 2 months, fibrocartilaginous tissue developed inside the implants, whereas control defects only showed repair with fibrous tissue. Both type I and type II collagen, the two major collagen types of normal meniscal fibrocartilage, could be detected in this newly formed fibrocartilage. The implant guided vascular tissue from the periphery towards the lesion resulting in healing of the tear. After fibrocartilage had formed, vascularity decreased and was completely absent in mature fibrocartilage. Control defects remained filled with vascular connective tissue. Two-thirds of the longitudinal lesions were found to be healed partially or completely. It is concluded that implantation of a porous polymer does enhance vascularity sufficiently to result in healing of meniscal lesions extending into the avascular part. Healing takes place by repair tissue strongly resembling normal meniscal fibrocartilage.

Meniscal replacement using a porous polymer prosthesis: a preliminary study in the dog.

A porous polyurethane prosthesis was used to replace the lateral meniscus in the dog. After an initial ingrowth of fibrous tissue, the prostheses became filled with tissue strongly resembling normal meniscal fibrocartilage. Although less severe than seen after total meniscectomy, cartilage degeneration was frequent, possibly because tissue ingrowth in the prostheses occurred too slowly. Porous polymers can be useful for replacement of the meniscus, provided that chemical and physical properties are optimized.

Use of porous polyurethanes for meniscal reconstruction and meniscal prostheses.

In the past, porous materials made of an aromatic polyurethane (PU) were successfully used to meniscal reconstruction in dogs. Since aromatic PUs yield very toxic fragments upon degradation, a linear PU was synthesized by curing a poly(epsilon-caprolactone) and 1,4-trans-cyclohexane diisocyanate based prepolymer with cyclohexanedimethanol. Porous materials of this polymer were also implanted for meniscal reconstruction. The results were comparable with the most successful implant series so far. Additionally, a porous meniscal prosthesis was developed to replace a total meniscus. Due to the very high shear stresses to which the prosthesis would be exposed, the stress hysteresis phenomenon linear PUs are known to exhibit could be of great consequence. Therefore an aliphatic PU network, synthesized by cross-linking poly(epsilon-caprolactone) and 1,4-trans-cyclohexane diisocyanate with glycerol, was used. Dislocation caused by tearing out of the sutures was found to be a problem because the tear resistance of the material was relatively low. In this study the tearing problem has been partly circumvented by using a complex suturing technique. Meniscal prostheses turned out to induce fibrocartilage upon implantation, and degeneration of articular cartilage was less severe than after meniscectomy.

Porous implants for knee joint meniscus reconstruction: a preliminary study on the role of pore sizes in ingrowth and differentiation of fibrocartilage.

Implants with four different macropore sizes were implanted in the meniscus of 29 rabbits for assessment of ingrowth and differentiation of fibrocartilage. Implant macropores were 50-90, 90-150, 150-250 and 250-500 mum, the vol.% macropores was 48-55 and total pore volume 84-86 vol.%. Ingrowth was optimal in the two large pore implants whereas the small pore implants partially remained empty up to 1 year post-operative. Capsule formation and the foreign body reaction was severe for the small pore implants whereas this occurred to a lesser extent in the two large pore implants. Fibrocartilage formation, as assessed by morphology and antibody labelling for type I and type II collagen, was observed in a similar way in all implant types. It is concluded that for optimal ingrowth and incorporation of partial or total meniscal prosthesis, macropore sizes must be in the range of 150-500 mum.

Meniscal repair by fibrocartilage? An experimental study in the dog.

Longitudinal lesions in the avascular part of the dog's meniscus were repaired by implantation of a porous polyurethane. Ingrowing repair tissue was characterized by biochemical and immunological analysis. Histologically, repair tissue initially was composed of fibrous tissue containing type I collagen. After 3 months, fibrocartilaginous tissue developed inside the implants, whereas control defects only showed fibrous repair tissue. Both type I and II collagen, the major collagen types of normal meniscal fibrocartilage, could be detected in this newly formed fibrocartilage. It is concluded that fibrocartilage resembling normal meniscal tissue is formed and that longitudinal lesions can be healed after meniscal repair by implantation of a porous polymer.

Secondary retention of permanent molars: an assessment of ankylosis by scanning electron and light microscopy.

Secondary retention refers to the cessation of eruption of a tooth after emergence. This may be the result of pathological changes in the periodontal ligament. The aim of this study was to describe the morphological and histological aspects of the radicular surface of secondarily retained permanent molars. The roots of 12 secondarily retained molars and two control molars, were examined by means of scanning electron microscopy (SEM) and light microscopy (LM) in order to analyse the occurrence and localisation of ankylosis. With SEM it was observed that the root surface of retained molars showed local areas covered with bonelike tissue. LM of these areas showed that this tissue was bone in direct contact with the root surface (ankylosis). In 11 cases, the areas of ankylosis were observed in the bifurcation area and at the interradicular root surface. In the remaining case, ankylosis was located at the outer root surface. The results of this study endorse the assumption that focal ankylosis is an important factor in secondary retention. Treatment recommendations must be based on this fundamental principle, because orthodontic movement of ankylotic molars is not possible.

Porous polymer implants for repair of full-thickness defects of articular cartilage: an experimental study in rabbit and dog.

Full-thickness defects of articular cartilage were repaired by implantation of porous polymer implants in rabbits and dogs. The quality of the repair tissue was determined by collagen typing with antibodies. Implants with varying pore sizes and chemical composition were used. The effect of loading and motion was determined by inserting implants higher than, level with and lower than the surrounding cartilage. It appeared that healing took place by formation of fibrocartilaginous repair tissue containing both type I and type II collagen. Hyaline cartilage was observed in a minority of the rabbits used but not in the dog. Fibrocartilage formation in the dog was simulated by implantation of a porous polymer. Chemical composition of the polymer did not alter the results, neither did loading of the implant. It is concluded that the formation of fibrocartilaginous repair cartilage is stimulated by implantation of a porous polymer. This tissue seemed to function adequately in the dog but did show signs of degeneration in the rabbit.

Porous polymer implant for repair of meniscal lesions: a preliminary study in dogs.

Artificial meniscal lesions extending into the avascular part of the meniscus, which do not heal by any other means, were repaired by suturing either a porous polymer implant or a synovial flap into the defect. The implant guided the ingrowth of vascular repair tissue into the defect. This fibrous tissue later on transformed into fibrocartilage. Reconstruction with a synovial flap was not successful. It appeared that healing can be achieved by implantation of a porous polymer implant in a large number of cases. Future research will be aiming at improvement of the results of meniscal repair and application of this type of polymer for repair of cartilage defects.

Degradation of and tissue reaction to biodegradable poly(L-lactide) for use as internal fixation of fractures: a study in rats.

Samples of high-molecular-weight poly(L-lactide) (PLLA) (Mv = 9.0 x 10(5), a biomaterial developed for plates and screws used in internal fixation of jaw fractures, were implanted subcutaneously in the backs of rats to study tissue reaction to PLLA and to follow the degradation process. The PLLA seemed to follow the degradation pattern typical of biodegradable polyesters. After pure hydrolysis up to about 104 wk, phagocytic activity of macrophages was found at about 143 wk. Full resorption of PLLA was not demonstrated in this study. Except for the early and final parts of the implant period, no acute or chronic inflammatory reaction was observed. No implant was rejected. It is estimated that more than 3 yr will be required for total resorption of PLLA. For bone-healing this long period is of no practical importance. There is no need for removal of PLLA after fracture healing as is the case with metal fixation devices. Thus, PLLA has potential application in internal fixation of fractures and osteotomies in the maxillofacial region and other fractures that are not too heavily loaded in the human body.

Poly(L-lactide) implants in repair of defects of the orbital floor: an animal study.

Because of the life-long presence of alloplastic, nonresorbable orbital floor implants and the complications of their use mentioned in literature, the use of a resorbable material appears to be preferable in the repair of orbital floor defects. A high-molecular-weight, as-polymerized poly(L-lactide) (PLLA) was used for repair of orbital floor defects of the blowout type in goats. An artificial defect was created in the bony floor of both orbits. Reconstruction of the orbital floor was then carried out using a concave PLLA implant of 0.4-mm thickness. At 3, 6, 12, 19, 26, 52, and 78 weeks postoperatively, one goat was killed. Microscopic examination showed full encapsulation of the implant by connective tissue after 3 weeks. After 6 weeks, resorption and remodeling of the bone at the points of support of the implant could be detected. A differentiation between the sinus and orbital sides of the connective tissue capsule was observed. The orbital side showed a significantly more dense capsule than the antral side, which had a loose appearance. At 19 weeks, a bony plate was progressively being formed, and at 78 weeks, new bone had fully covered the plate on the antral and orbital side. No inflammation or rejection of the PLLA implant was seen.

Bone-plates and screws of bioabsorbable poly (L-lactide)--an animal pilot study.

Poly (L-lactide), a polymer of lactic acid (PLLA), with an extremely high molecular weight (Mv up to 1 x 10(6] has been synthesised under strictly controlled conditions resulting in a new microporous material with excellent mechanical properties. Bone-plates and screws machined from PLLA were used for fixation of two artificial mandibular fractures in sheep effected by a specially designed bone clamp. Fracture healing was uneventful without visible callus formation. Plates and screws of PLLA gave good stability over a sufficiently long period to enable normal fracture healing. Application in humans seems to be justified.

Secondary retention of permanent molars: a histologic study.

The etiology of secondary retention is not well understood, but ankylosis is often considered to be an important factor in primary molars. Data concerning the mechanism of secondary retention in the permanent dentition are insufficient, although a possible role of ankylosis has been suggested. In order to analyze the frequency of occurrence and localization of ankylosis in secondarily retained permanent teeth, 26 secondarily retained molars and for comparison six normal molars were studied histologically. These data were compared with the clinical and radiographic findings. Areas of ankylosis were observed along the roots of all secondarily retained molars. In 81% of the cases these areas were located at the bifurcation and interradicular root surface. No signs of ankylosis were found in normal molars. When these results were compared with the clinical and radiographic data, it was obvious that the latter gave many false negative results, because the areas of ankylosis were often too small to be detected clinically or radiographically.