Interaction-Transformation Evolutionary Algorithm for Symbolic Regression.

Interaction-Transformation (IT) is a new representation for Symbolic Regression that reduces the space of solutions to a set of expressions that follow a specific structure. The potential of this representation was illustrated in prior work with the algorithm called SymTree. This algorithm starts with a simple linear model and incrementally introduces new transformed features until a stop criterion is met. While the results obtained by this algorithm were competitive with the literature, it had the drawback of not scaling well with the problem dimension. This article introduces a mutation-only Evolutionary Algorithm, called ITEA, capable of evolving a population of IT expressions. One advantage of this algorithm is that it enables the user to specify the maximum number of terms in an expression. In order to verify the competitiveness of this approach, ITEA is compared to linear, nonlinear, and Symbolic Regression models from the literature. The results indicate that ITEA is capable of finding equal or better approximations than other Symbolic Regression models while being competitive to state-of-the-art nonlinear models. Additionally, since this representation follows a specific structure, it is possible to extract the importance of each original feature of a data set as an analytical function, enabling us to automate the explanation of any prediction. In conclusion, ITEA is competitive when comparing to regression models with the additional benefit of automating the extraction of additional information of the generated models.

Forest pit viper (Bothriopsis bilineata bilineata) bite in the Brazilian Amazon with acute kidney injury and persistent thrombocytopenia.

There are six species of Bothriopsis in Latin America, accidents caused by this genus are unusually reported. A 37-year-old man admitted thirty hours after a snakebite to the emergency department of Santarém City Hospital (SCH), northern Brazil. The patient presented local erythema, edema, increased local temperature and blister with serous fluid in the right arm. He developed acute kidney injury (AKI) and prolonged thrombocytopenia. The blood was incoagulable and he was treated with anti-bothropic antivenom and antibiotics. The patient had complete regression of all clinical and laboratory manifestations at varying intervals. The platelet counts returned to normal almost 2 weeks after administration of specific antivenom. The present report is the first accident caused by a snake of forest pit viper (Bothriopsis bilineata) in the Brazilian Amazon forest.

Epidemiologic and clinical survey of victims of centipede stings admitted to Hospital Vital Brazil (São Paulo, Brazil).

We retrospectively analyzed 98 proven cases of centipede stings admitted to Hospital Vital Brazil, Butantan Institute, São Paulo, Brazil, between 1990 and 2007. Most stings occurred at the metropolitan area of São Paulo city (n=94, 95.9%), in the domiciles of patients (n=67, 68.4%), and during the warm-rainy season (n=60, 61.2%). The mean age of the victims was 32.0+/-18.8-years-old. Cryptops and Otostigmus genera were responsible for most cases. Around 86% of the patients sought medical care within 6h after the sting. Both lower (56.1 %) and upper limbs (41.8 %) were most frequently bitten, especially the feet and hands (89.8%). The most frequent local clinical manifestations were pain (94.9%), erythema (44.9%) and edema (21.4%), and the latter was mainly observed in patients bitten by Otostigmus spp. Supportive treatment was used in only 28.6% of the patients, namely administration of local anesthesia (9.2%) and systemic analgesia (13.3%). No sequels or complications were observed in patients, and the prognostic was benign.

Failure of chloramphenicol prophylaxis to reduce the frequency of abscess formation as a complication of envenoming by Bothrops snakes in Brazil: a double-blind randomized controlled trial.

Bites by many species of venomous snake may result in local necrosis at, or extending from, the site of the bite. The use of prophylactic antibiotics to prevent infection as a complication of local necrotic envenoming is controversial. A double-blind randomized controlled trial was carried out to assess whether antibiotic therapy is effective in this situation. Two hundred and fifty-one patients, with proven envenoming by snakes of the genus Bothrops, admitted to two hospitals in Brazil, between 1990 and 1996, were randomized to receive either oral chloramphenicol (500 mg every six hours for five days) or placebo. One hundred and twenty-two of these patients received chloramphenicol (group 1) and 129 were given placebo (group 2). There were no significant differences between the groups at the time of admission. Necrosis developed in seven (5.7%) patients in group 1 and in five (3.9%) patients in group 2 (P>0.05) while abscesses occurred in six patients (4.9%) in group 1 and in six (4.7%) patients in group 2 (P>0.05). In conclusion, the use of orally-administered chloramphenicol for victims of Bothrops snake bite with signs of local envenoming on admission, is not effective for the prevention of local infections.

Envenoming by Bothrops jararaca in Brazil: association between venom antigenaemia and severity at admission to hospital.

The association between the clinical severity of Bothrops jararaca envenoming at admission and serum venom and plasma fibrinogen concentrations before antivenom administration is reported in 137 patients admitted to Hospital Vital Brazil, Instituto Butantan, São Paulo, Brazil, between 1989 and 1990. Other variables such as age, gender, site of the bite, use of tourniquet and the time interval between the bite and start of antivenom therapy, spontaneous systemic bleeding, and the 20 minute whole blood clotting test (20WBCT) at admission showed no association with either severity or serum venom antigen concentration (SVAC). Mean SVAC in patients with mild envenoming was significantly lower than in the group with moderate envenoming (P = 0.0007). Patients with plasma fibrinogen concentrations > 1.5 g/L had a lower mean SVAC than patients with plasma fibrinogen concentrations < or = 1.5 g/L (P = 0.02). Those admitted with a tourniquet in place had significantly higher plasma fibrinogen concentrations than those without a tourniquet (P = 0.002). A multiple logistic regression model showed independent risk factors for severity: bites at sites other than legs or forearms, SVACs > or = 400 ng/mL, and the use of a tourniquet. Rapid quantification of SVAC before antivenom therapy might improve initial evaluation of severity in B. jararaca bites.

Heparin-antivenom association: differential neutralization effectiveness in Bothrops atrox and Bothrops erythromelas envenoming.

Heparin, in some regions of Brazil has been used in the treatment of bothropic accidents, but the data found in the literature are inconclusive about its effectiveness. The venoms of Bothrops atrox and of B. erythromelas were characterized according to their biological activities. The capacity of heparin in neutralizing these activities was tested with doses of 3 and 6 IU in isolated form and associated to Antibothropic Serum (ABS). It was verified that heparin, in doses of 3 and 6 IU, was not effective in neutralizing the desfibrinating and edema-forming activities of B. atrox venom and the hemorrhagic and coagulant actions of both venoms. Heparin diminished the effectiveness of the ABS in the neutralization of the hemorrhagic and edema-forming activities of the B. atrox venom. However, heparin in the 6 IU dose was capable of neutralize the edema-forming of the B. erythromelas and increase the effectiveness of the ABS. Heparin also neutralized the phospholipasic A2 activity of B. atrox (14.3%) and B. erythromelas (28.0%) venoms. For B. erythromelas venom, the associated treatment, heparin and ABS, was more effective in the neutralization of its lethal activity.

[The evaluation of the efficacy of azithromycin and pyrimethamine used alone or in combination in the treatment of an experimental infection in mice by Toxoplasma gondii]. / Avaliação da eficácia da azitromicina e da pirimetamina, usadas isolada ou associadamente, no tratamento de infecção experimental de camundongos pelo Toxoplasma gondii.

The efficacy of azithromycin and pyrimethamine in experimental infection of mice with Toxoplasma gondii was tested. Daily dosages of 200 mg/kg and 12.5 mg/kg, respectively, were given orally over a period of ten days. The medications were administered in combination or separately. The combined use of the drugs yielded better results, and a similar investigation using a cystogenic strain of the parasite will be conducted in a future study.

Sequential randomised and double blind trial of promethazine prophylaxis against early anaphylactic reactions to antivenom for bothrops snake bites.

OBJECTIVE: To investigate the efficacy of the H1 antihistamine promethazine against early anaphylactic reactions to antivenom. DESIGN: Sequential randomised, double blind, placebo controlled trial. SETTING: Public hospital in a venom research institute, São Paulo, Brazil. PARTICIPANTS: 101 patients requiring antivenom treatment after being bitten by bothrops snakes. INTERVENTION: Intramuscular injection of promethazine (25 mg for adults and 0.5/kg for children) or placebo given 15-20 min before starting intravenous infusion of antivenom. MAIN OUTCOME MEASURES: Incidence and severity of anaphylactic reactions occurring within 24 hours after antivenom. RESULTS: Reactions occurred in 12 of 49 patients treated with promethazine (24%) and in 13 of 52 given placebo (25%); most were mild or moderate. Continuous sequential analysis indicated that the study could be interrupted at the 22nd untied pair, without preference for promethazine or placebo. CONCLUSION: Prophylaxis with promethazine does not prevent early reactions. Patients should be observed carefully during antivenom infusion and the subsequent few hours.

A clinical and epidemiological study of Loxosceles spider envenoming in Santa Catarina, Brazil.

A clinical and epidemiological study of 267 cases of envenomation by Loxosceles spp. (loxoscelism), notified to Centro de Informações Toxicológicas de Florianópolis (Santa Catarina State, Brazil), was conducted between January 1985 and December 1995. Most of the incidents occurred along the coast of the mid-southern region of the state, during the warmest months. L. laeta and L. intermedia were identified as the causative agents. Cutaneous loxoscelism was clinically diagnosed in 232 (86.9%) patients with local pain (86.5%), oedema (80.5%), hyperaemia (79.8%) and necrosis (56.9%). Cutaneous-visceral loxoscelism was detected in 35 patients (13.1%) with intravascular haemolysis, manifested by jaundice (68.6%), oliguria (45.7%), dark urine (28.6%), haemorrhage (25.7%), anuria (8.6%) and shock (2.9%), besides the cutaneous effects. Specific antivenom was given to 125 patients (46.8%) and only 8 (6.5%) had mild reactions. Acute renal failure was observed in 17 cases (6.4%); 4 patients (1.5%) died, all of whom were children under 14 years old.

Snake bites by the jararacuçu (Bothrops jararacussu): clinicopathological studies of 29 proven cases in São Paulo State, Brazil.

The jararacuçu, one of the most dreaded snakes of Brazil, southern Bolivia, Paraguay and northeastern Argentina, is a heavily-built pit viper which may grow to a length of 2.2 m. Up to 1000 mg (dry weight) of highly-lethal venom may be milked from its venom glands on a single occasion. It has accounted for 0.8% to 10% of series of snake bites in São Paulo State, Brazil. We examined 29 cases of proven jararacuçu bites recruited over a 20-year period in two São Paulo hospitals. Severe signs of local and systemic envenoming, (local necrosis, shock, spontaneous systemic bleeding, renal failure) were seen only in patients bitten by snakes longer than 50 cm; bites by shorter specimens were more likely to cause incoagulable blood. Fourteen patients developed coagulopathy, six local necrosis (requiring amputation in one) and five local abscesses. Two became shocked and four developed renal failure. Three patients, aged 3, 11 and 65 years, died 18.75, 27.75 and 83 h after being bitten, with respiratory and circulatory failure despite large doses of specific antivenom and intensive-care-unit management. In two patients, autopsies revealed acute renal tubular necrosis, cerebral oedema, haemorrhagic rhabdomyolysis at the site of the bite and disseminated intravascular coagulation. In one survivor with chronic renal failure, renal biopsy showed bilateral cortical necrosis; the patient remains dependent on haemodialysis. Effects of polyspecific Bothrops antivenom were not impressive, and it has been suggested that anti-Bothrops and anti-Crotalus antivenoms should be given in combination.

A randomized 'blinded' comparison of two doses of antivenom in the treatment of Bothrops envenoming in São Paulo, Brazil.

An earlier study in São Paulo state suggested that the dose for patients with mild or moderate envenoming by Bothrops snakes (mainly Bothrops jararaca) could be effectively decreased to 4 ampoules (40 mL) of Brazilian Brothrops polyspecific antivenom. The present 'blinded' study examined the lowest dose studied in the first trial (equivalent to 4 x 10 mL ampoules) and half that dose of antivenom (equivalent to 2 x 10 mL ampoules) in 2 similar groups of 170 patients who were comparable in all respects before treatment. The majority of patients showed rapid clinical improvement after treatment with either dose regimen and rapid restoration of blood coagulability and cessation of bleeding. There was no apparent difference between the 2 groups of patients in any respect. The study confirmed that, in such patients, the dose of antivenom can be decreased from 4 ampoules to 2 ampoules without reduction of therapeutic efficacy, and it is highly likely that this reduction will result in a decrease of early anaphylactic reactions caused by the antivenom.

Reliability of the simple 20 minute whole blood clotting test (WBCT20) as an indicator of low plasma fibrinogen concentration in patients envenomed by Bothrops snakes. Butantan Institute Antivenom Study Group.

Reliability of the simple 20 minute whole blood clotting test (WBCT20) as an indicator of low plasma fibrinogen concentration in patients envenomed by Bothrops snakes. Toxicon 32, 1045-1050, 1994.--A simple whole blood clotting test (WBCT20) was assessed for its efficacy in determination of severe defibrinogenation in patients envenomed by Bothrops snakes in Brazil. There was a close relationship between the results of the WBCT20 and plasma fibrinogen levels in 69 moderately envenomed patients. The advantage of the WBCT20 over estimation of plasma fibrinogen concentrations in patients is that it is a simpler, faster and more reliable test. It is also of use in assessing the effectiveness of antivenom therapy in relation to the restoration of blood coagulability.

Severe and fatal mass attacks by 'killer' bees (Africanized honey bees--Apis mellifera scutellata) in Brazil: clinicopathological studies with measurement of serum venom concentrations.

In São Paulo State, Brazil, five males, aged between 8 and 64 years, were attacked by 'Africanized' honey bees (Apis mellifera scutellata). The estimated number of stings received by each patient ranged from > 200 to > 1000. All five were transferred to intensive care units in São Paulo City. Clinical features included intravascular haemolysis, respiratory distress with ARDS, hepatic dysfunction, rhabdomyolysis (with myoglobinaemia and myoglobinuria), hypertension and myocardial damage (perhaps explained by release of endogenous catecholamines by venom phospholipase A2 and mellitin), shock, coma, acute renal failure and bleeding. Laboratory findings included gross neutrophil leucocytosis, elevated serum enzymes [AST, ALT, LDH, CPK (predominantly CPK-MM)] and creatinine. Clotting times were slightly prolonged. Despite treatment with antihistamines, corticosteroids, bronchodilators, vasodilators, bicarbonate, mannitol and mechanical ventilation, three of the patients died between 22 and 71 h after the attacks, with histopathological features of ARDS, hepatocellular necrosis, acute tubular necrosis, focal subendocardial necrosis and disseminated intravascular coagulation. Whole bee venom and phospholipase A2 (PLA2) antigen concentrations were measured in serum and urine for the first time, using enzyme immunoassay. High venom and PLA2 concentrations were detected in serum and urine for more than 50 h after the stings in two fatal cases, in one of which the total circulating unbound whole venom was estimated at 27 mg, one hour after the attack. An antivenom should be developed to treat the increasing numbers of victims of mass attacks by Africanized 'killer' bees in USA, Middle and South America.

Randomized comparative trial of three antivenoms in the treatment of envenoming by lance-headed vipers (Bothrops jararaca) in São Paulo, Brazil.

In São Paulo City, Brazil, 121 patients with moderately severe envenoming by Bothrops snakes (principally B. jararaca) were randomized for treatment with Brazilian polyspecific Bothrops antivenoms: Instituto Butantan (39 patients), Instituto Vital Brazil (41), Fundação Ezequiel Dias (FUNED) (41). The initial dose was four ampoules (40 ml) in 89 patients with less severe envenoming and eight ampoules (80 ml) in 32 patients with more severe envenoming. A second dose of four ampoules was required in 20 patients. Patients receiving the three antivenoms were comparable in all respects before treatment. There were no deaths. The majority showed rapid clinical improvement, resolution of local envenoming, cessation of bleeding and restoration of blood coagulability. No differences in the efficacy of the three antivenoms were revealed by clinical or laboratory observations, including measures of haematological, haemostatic and biochemical abnormalities. Twelve patients developed abscesses (Butantan 1, Vital Brazil 6, FUNED 5) and seven developed local necrosis (3,1,3). Of 88 patients followed up 20-30 days after the bite 33 (37.5%) still had symptoms or signs of local envenoming, especially swelling. Early (anaphylactic) reactions were unexpectedly frequent after all three antivenoms but were significantly more frequent with Butantan (87%) than with Vital Brazil (37%) or FUNED (56%) antivenoms (p < 0.001). A possible explanation was the higher total protein content and percentage immunoglobulin of Butantan antivenom. The doses of antivenom recommended in Brazil and used in this study may be unnecessarily high, resulting in an unacceptably high incidence of reactions. Results of the study should prompt a critical re-evaluation of antivenom production techniques and dosage recommendations in Brazil.

Toxic activities of venoms from nine Bothrops species and their correlation with lethality and necrosis.

The comparison of seven toxic activities contained in venoms from nine different species of Bothrops and the correlation of each activity with lethality and necrosis was the subject of this study. The haemorrhagic, coagulant, necrotizing, myotoxic, proteolytic and phospholipase activities were not equally distributed among the venoms studied except for the oedema-inducing activity which was almost equally distributed among them. The correlation coefficient was estimated for each activity in relation to lethality and necrosis induced by the venom. Lethality was significantly related to haemorrhagic and oedema-inducing activities, whereas the necrotizing activity showed significant correlation with phospholipase and coagulant activities. Proteolytic activity presented a significant inverse correlation with lethality.

Loxoscelismo: estudo de 242 casos (1980-1984) / Loxoscelism: study of 242 cases (1980-1984)

Foram analisados 242 acidentes atribuídos a aranhas do gênero Loxosceles Heinecken & Lowe atendidos no Hospital Vital Brazil do Instituto Butantan (1980-1984). L. gaucho Gertsch foi o agente agresssor mais comum e a espécie capturada com maior frequência nos locais de acidente vistoriados. L. laeta e L. intermedia Mello-Leitäo também estiveram representados no material estudado. Noçöes de reconhecimento e biologia dessas aranhas assim como a distribuiçäo geográfica das espécies brasileiras foram incluídas, para orientaçäo de médicos e pessoal relacionado a acidentes por animais peçonhentos. Os sinais característicos de síndrome loxoscélica e sua frequência na casuística em estudo foram mencionados e uma comparaçäo foi feita com dados correspondentes encontrados na literatura sulamericana