Control of chaotic systems by deep reinforcement learning.

Deep reinforcement learning (DRL) is applied to control a nonlinear, chaotic system governed by the one-dimensional Kuramoto-Sivashinsky (KS) equation. DRL uses reinforcement learning principles for the determination of optimal control solutions and deep neural networks for approximating the value function and the control policy. Recent applications have shown that DRL may achieve superhuman performance in complex cognitive tasks. In this work, we show that using restricted localized actuation, partial knowledge of the state based on limited sensor measurements and model-free DRL controllers, it is possible to stabilize the dynamics of the KS system around its unstable fixed solutions, here considered as target states. The robustness of the controllers is tested by considering several trajectories in the phase space emanating from different initial conditions; we show that DRL is always capable of driving and stabilizing the dynamics around target states. The possibility of controlling the KS system in the chaotic regime by using a DRL strategy solely relying on local measurements suggests the extension of the application of RL methods to the control of more complex systems such as drag reduction in bluff-body wakes or the enhancement/diminution of turbulent mixing.

Isotopically Labeled Nanoparticles at Relevant Concentrations: How Low Can We Go? The Case of CdSe/ZnS QDs in Surface Waters.

Analytical barriers impose work at nanoparticles (NPs) concentrations orders of magnitude higher than the expected NPs concentrations in the environment. To overcome these limitations, the use of nontraditional stable isotope tracers incorporated in NPs (spiked-NPs) coupled with HR-ICP-MS has been proposed. The performance and efficiency of this analytical method was assessed in the case of quantum dots (QDs). Multi-isotopically labeled 111Cd77Se/68ZnS QDs were synthesized and their dissemination in natural aquatic matrices (river, estuarine and sea waters) was modeled at very low concentrations (from 0.1 to 5000 ppt). The QD limits of quantification (QD-LOQ) in each matrix were calculated according to the isotopic tracer. In ultrapure and simple medium (HNO3 2%), Zn, Cd, and Se originated from the QDs were quantifiable at concentrations of 10, 0.3, and 6 ppt, respectively, which are lower than the conventional HR-ICP-MS LOQs. In aquatic matrices, the QD-LOQs increase 10-, 130-, and 250-fold for Zn, Cd, and Se, respectively, but remain relevant of environmental concentrations (3.4 ppt ≤ QD-LOQs ≤ 2.5 ppb). These results validate the use of isotopically labeled ENPs at relevant concentrations in experimental studies related to either their fate, behavior, or toxicity in most aquatic matrices.

Cyanobacterial formation of intracellular Ca-carbonates in undersaturated solutions.

Cyanobacteria have long been thought to induce the formation of Ca-carbonates as secondary by-products of their metabolic activity, by shifting the chemical composition of their extracellular environment to conditions favoring mineral precipitation. Some cyanobacterial species forming Ca-carbonates intracellularly were recently discovered. However, the environmental conditions under which this intracellular biomineralization process can occur and the impact of cyanobacterial species forming Ca-carbonates intracellularly on extracellular carbonatogenesis are not known. Here, we show that these cyanobacteria can form Ca-carbonates intracellularly while growing in extracellular solutions undersaturated with respect to all Ca-carbonate phases, that is, conditions thermodynamically unfavorable to mineral precipitation. This shows that intracellular Ca-carbonate biomineralization is an active process; that is, it costs energy provided by the cells. The cost of energy may be due to the active accumulation of Ca intracellularly. Moreover, unlike cyanobacterial strains that have been usually considered before by studies on Ca-carbonate biomineralization, cyanobacteria forming intracellular carbonates may slow down or hamper extracellular carbonatogenesis, by decreasing the saturation index of their extracellular solution following the buffering of the concentration of extracellular calcium to low levels.

[The PRKAG2 cardiac syndrome with familial hypertrophic cardiomyopathy: an inherited burden. A case report. Review of the literature]. / La cardiomyopathie hypertrophique familiale dans le contexte de la mutation PRKAG2 : un lourd héritage. A propos d'un cas. Revue de la littérature.

We report the case of a young man without prior medical history who presented with a left ventricular heart failure because of a new onset atrial fibrillation. The evolution is characterized by a sinus rythm dysfunction, a complete atrioventricular block, a non-sustained ventricular tachycardia (which required a dual-chamber defibrillator implantation) and an ischemic testicular necrosis treated by orchidectomy. After ruling out differential diagnosis we evoked an hypertrophic cardiomyopathy. Medical family anamnesis revealed an hereditary component, and we concluded to a PRKAG2 cardiac syndrome presenting as a familial hypertrophic cardiomyopathy. Two years later, he presented with a type B aortic dissection. We review the literature and differentials diagnosis.

Le cas que nous présentons est celui d'un jeune patient sans antécédent médical qui présente une décompensation cardiaque gauche sur fibrillation auriculaire de novo. L'évolution est caractérisée par une dysfonction sinusale, un bloc atrioventriculaire syncopal, de la tachycardie ventriculaire non soutenue avec nécessité d'implanter un défibrillateur double chambre et par une nécrose testiculaire d'origine ischémique indiquant une orchidectomie. Plusieurs diagnostics différentiels sont évoqués. Les investigations plus poussées mettent en évidence une cardiomyopathie hypertrophique jusqu'alors asymptomatique. L'anamnèse familiale révèle une composante héréditaire qui nous amènera à évoquer le diagnostic de cardiomyopathie hypertrophique familiale liée à la mutation PRKAG2. Deux ans plus tard, il se présente avec une dissection aortique de type B. La littérature concernant cette pathologie et les diagnostics différentiels sont revus à cette occasion.

Hyperglycemia is a risk factor for high-grade envenomations after European viper bites (Vipera spp.) in children.

CONTEXT: Hyperglycemia has been described in severe scorpion envenomation, we wanted to analyze if it was applicable to viper bites in children. AIM: To describe clinical, biological, and therapeutic characteristics of 83 children bitten by European viper (Vipera spp.) and to confirm that hyperglycemia is a risk factor for high-grade envenomation. MATERIAL AND METHODS: A retrospective study was conducted between 2001 and 2014 in the pediatric emergency department of a tertiary level children's hospital. Collected data were: age and sex of children; day and time of admission; day, time and circumstances of the accident; snake identification; bite location; envenomation severity; presence of fang marks; prehospital care; laboratory abnormalities, use of specific immunotherapy, associated treatments; length of stay; hospital course. RESULTS: Eighty-three children were included (62 boys, 21 girls). The mean age was 7.4 ± 3.9 years. Bites were most often located on the lower extremities (66%). The classification of envenomation was: 83% low grade (absent or minor envenomation) and 17% high grade (moderate to severe envenomation). All high-grade envenomations received specific immunotherapy (Viperfav(TM), (Aventis Pasteur, MSD, Lyon, France). Being bitten on an upper extremity (odds ratio [OR] 51.1 95% class interval [CI] [6.1-424], p < 0.0001), during the afternoon (OR 13.4 95% CI [1.7-107.9], p = 0.015), feeling violent pain (OR 4.2 95% CI [1.1-16.5], p = 0.023), and high initial plasma glucose level (6.5 ± 1.7 mmol/L versus 5.0 ± 0.9 mmol/L, p = 0.027) were associated with a significant risk of high-grade envenomation. CONCLUSION: We have confirmed a potential link between initial hyperglycemia and the risk of progression to high-grade envenomation as well as its association with other published predictive factors.

European viper envenomation recorded by French poison control centers: A clinical assessment and management study.

INTRODUCTION: Immunotherapy is the gold standard treatment for patients bitten by European vipers in France; it significantly decreases morbidity, frequency and severity of complications and length of stay. A national prospective study was performed by all Poison Control Centers (PCC) to validate the emergency protocol for viper envenomations. METHODS: This prospective study included all cases of viper bites in France, treated or not with Viperfav(®) in 2013. RESULTS: In 2013, 277 cases of viper bites were collected: ratio M/F 2.1; mean aged 43 years (<15 years 25% 15-65 63% > 65 12%). The final severity was divided into 68 grades 0, 58 grades I, 62 grades IIA, 71 grades IIB and 18 grades III. One death was reported. Five patients had neurological signs. For the 114 patients who received Viperfav(®), all systemic signs disappeared in 5 h and in 24 h for biological and neurological signs. No severe anaphylactic reaction with Viperfav(®) was reported. Late Viperfav(®) administration increased the risk of functional impairment 15 days after the bite (OR = 3.21 p = 0.043). The administration of Low Molecular Weight Heparin (LMWH) increased the frequency of functional impairment to 15 days after the bite (OR = 6.38 p = 0.064), although Viperfav(®) was given in the first 18 h. DISCUSSION: This study confirms the efficiency, safety and recommendation of an early administration of a single dose of Viperfav(®), LMWH should not be used. It also shows the extension of neurotoxic venom of vipers in France.

Behavior and fate of industrial zinc oxide nanoparticles in a carbonate-rich river water.

The present study precisely describes the solubility patterns of commercial uncoated and organic coated ZnO NPs (nc-NPs and c-NPs, respectively) in a natural carbonate-rich water and the physicochemical processes involved. NPs transformation rates were determined with the Donnan Membrane approach (DMT, to obtain Zn(2+) concentration) and ultrafiltration (i.e. Zn(2+) and Zn bound to small organic ligands) and modeled with VMinteQ. XPS measurements evidenced the presence on native nc-NPs of a Zn(OH)2 layer which accounts for almost 22% of total Zn. This Zn(OH)2 phase is more soluble than ZnO, and could control the early dissolution steps of the nc-NPs in our system. Indeed, nc-NPs display a fast (<1 h) dissolution step reaching 19 µM Zn in solution (<1% of the total initial zinc concentration). Comparatively, c-NPs progressively release zinc during the first 48 h, to finally reach a maximum of 197 µM (10% of total Zn), which is 10 times the maximum value measured for nc-NPs. Over the long term, dissolved Zn concentrations decrease in both systems, corresponding to the neoformation of carbonate phases observed by TEM imaging. The kinetic modeling allows highlighting two different ranges of time, corresponding to (i) first 10h with a fast precipitation (kp(')=-182.10(-4)) related to a highly oversaturated solution with respect to carbonate zinc mineral and (ii) a second slower precipitation step (kp(')=-8.10(-4)), related to the embedding of NPs in the precipitated carbonate matrix. The steady state is reached after 3 months of interaction.

[Pediatric adder bites]. / Morsures de vipères chez l'enfant.

UNLABELLED: Adder bites and their progression to severe envenomations are more frequent in children than in adults. AIM: To describe the clinical, biological, and therapeutic characteristics of children bitten by adders and to identify risk factors associated with severe envenomations corresponding to grades II and III of the Audebert et al. classification (Toxicon 1992). MATERIAL AND METHODS: A retrospective study was conducted between 2001 and 2009 in the pediatric emergency department of a tertiary children's hospital. The data collected were: age and sex of children; day and time of admission; day, time, and circumstances of the accident; snake identification; bite location; envenomation severity based on the Audebert et al. classification; presence of fang marks; prehospital care; use of specific immunotherapy (Viperfav(®)), associated treatments; length of stay; orientation, progression, and any complications. RESULTS: Fifty-eight children were included (43 boys, 15 girls). The mean age was 7.8 ± 4.1 years (range, 1.8-15 years). Bites occurred more often between 12:00 pm and 6:00 pm (62%), and were most often located in the lower extremities (77%). The classification of envenomation was: 83% low grade (grade 0, absence of envenomation, fang marks present; grade I, minor envenomation) and 17% high grade (grades II and III, moderate and severe envenomations). All high-grade envenomations received specific immunotherapy (Viperfav(®) F(ab')(2) fragments against Vipera aspis, Vipera berus, and Vipera ammodytes). The mean time from bite to Viperfav(®) injection was 23 ± 11 h (range, 8-36 h). Being bitten on the upper extremities (p < 0.001), during the afternoon (p = 0.025), feeling an immediate violent pain (p = 0.037), and high initial glycemia (p = 0.016) were associated with a significant risk of progressing to high-grade envenomation. There was no significant correlation between age, gender, and upper extremity bite. In the final model of the multivariate statistical analysis, three factors remained associated with this risk: bite location in the upper extremities (relative risk [RR] = 60.5 [3.5-1040[; p = 0.005), immediate violent pain (RR = 21.5 [1.3-364.5[; p = 0.03), and female gender (RR = 17.5 [0.9-320.3[; p = 0.053). CONCLUSION: A certain number of criteria seem related with a more significant risk of progression to high-grade envenomation following an adder bite. These results need to be studied on a larger cohort of patients. Bites to the upper extremities should be handled with caution because of the association with more severe envenomation.

Interferon-gamma releasing assay versus tuberculin skin testing for latent tuberculosis infection in targeted screening programs for high risk immigrants.

BACKGROUND: Recent immigrants from developing countries (<2 years since immigration) are at very high risk of active TB disease due to reactivation of latent infections acquired in the country of origin. In industrialized low-incidence TB countries targeted testing programs for high risk groups could allow the detection of latently infected persons who would likely benefit from a course of preventive treatment. In this study we evaluated the tuberculin skin test (TST) and interferon-gamma enzyme-linked immunosorbent assay (QuantiFERON TB-gold in tube, QFT-IT) strategies for TB infection screening programs in recent immigrants from highly endemic countries. PATIENTS AND METHODS: This is a prospective cross-sectional study. Paired tests performed in 1,130 immigrants attending an outpatient ward, between 2005 and 2007 for any health problem were evaluated by intention-to-treat (ITT) and per-protocol (PP) analysis for efficiency and efficacy of screening program. RESULTS: Positive TST and QFT-IT were observed in 36.04 versus 29.82% (ITT) and in 45.27 versus 30.22% (PP) respectively. A higher drop-out rate was observed for TST (20.35 vs. 1.33%) (p < 0.0001). Second level assessment was accepted by half of the TST positive patients. Overall agreement rate between 887 paired tests was fair (k = 0.38). Higher k values were observed for higher TB prevalence rate in the country of origin (k = 0.43), for TST induration diameters >20 mM (k = 0.47), in subjects aged 40-50 years (k = 0.41) and in unvaccinated persons (k = 0.40). In a multiple logistic regression model continent of origin, class of TB prevalence in the country of origin and contacts with TB patients were found to be significantly associated with the probability of TST and QFT-IT positive result. Low education levels were associated only to an increased risk of TST positive results. CONCLUSIONS: The drawback of the TST screening strategy in recent immigrants from highly endemic countries is due to low sensitivity/specificity of the test and to high drop-out rate with an overall significant lowering in strategy efficacy/efficiency. The higher QFT-IT specificity prevents unnecessary overload of the health care system and, although more expensive, might represent a cost-effective alternative to TST in targeted screening programs directed to high risk populations.

Antiretroviral treatment and age-related comorbidities in a cohort of older HIV-infected patients.

BACKGROUND: The availability of several therapeutic regimens has transformed HIV infection from a life-threatening disease into a chronic condition. Older patients (>50 years old) with HIV infection constitute a new treatment challenge in terms of the cumulative effects of ageing and antiretroviral therapy (ART). METHODS: The immunovirological effects and metabolic interactions of 48 weeks of ART in older patients followed up in three Infectious Diseases Units in Milan, Italy since 1994 were compared with those in younger controls aged 25-35 years. RESULTS: The 159 older patients and 118 controls enrolled in the study were comparable for HIV stage, baseline CD4 cell count and viral load but differed for mode of HIV transmission, comorbid conditions and related chronic treatments. Mean viral load decreased after 48 weeks of treatment by 2.6 log(10) HIV RNA copies/mL and CD4 count increased by 137.5 cells/microL in older patients, and similar values for immunovirological effects were obtained in the young controls. The relative risk (RR) of an abnormal test in older patients was 7.33 [95% confidence interval (CI) 4.36-12.36] for glucose, 1.73 (95% CI 1.45-2.07) for total cholesterol, 1.56 (95% CI 1.22-2.0) for high-density lipoprotein cholesterol, 1.26 (95% CI 1.02-1.56) for triglycerides, 6.48 (95% CI 4.36-9.66) for serum creatinine, and 0.45 (95% CI 0.35-0.58) for ALT. Moderate/severe liver and renal toxicities were recorded in the older patients but not in the controls. The tolerability of ART did not differ between the older patients and the controls. Thirty-nine new cardiovascular, endocrine-metabolic and neuralgic disorders (24.52 per 100 person-years) were diagnosed in the older patients and four (3.39 per 100 person-years) in the controls (P<0.0001). CONCLUSIONS: Diseases induced by, or related to, the toxic effects of antiretrovirals interact with age-specific health profiles, raising new questions and challenges. Comparative epidemiological studies, research studies addressing specific questions and surveillance are needed to answer the questions that arise in clinical monitoring.

Muscle-specific promoters may be necessary for adeno-associated virus-mediated gene transfer in the treatment of muscular dystrophies.

Recombinant adeno-associated virus (rAAV) vectors allow efficient gene transfer and expression in the muscle; therefore, rAAVs represent a potential gene therapy vector for muscular dystrophies. For further investigations, we used a mouse muscular dystrophy model (gsg(-/-) mice) gamma-sarcoglycan, a subunit of the dystrophin-glycoprotein complex, is missing. gsg(-/-) mice develop progressive dystrophy representative of a severe human phenotype disease. We previously showed high levels and stable expression of gamma-sarcoglycan in myofibers after direct muscle injection into gsg(-/-) mice of a recombinant AAV vector (AAV.dMCK.gSG) carrying the gamma-sarcoglycan cDNA driven by a muscle-specific promoter (truncated version of muscle creatine kinase). Here, we show that when gamma-sarcoglycan expression is driven by the ubiquitous cytomegalovirus (CMV) promoter (AAV.CMV.gSG), lower levels of transgene expression are observed and are associated with a humoral response to gamma-sarcoglycan. When using an rAAV vector, expressing the highly immunogenic product gamma-galactosidase under the CMV promoter (AAV.CMV.LacZ), we measured a strong cellular and humoral immune response to the transgene after intramuscular injection into gsg(-/-) mice. This study suggests that restriction of transgene expression to the muscle is an important criterion for the treatment of muscular dystrophies and will aid in the design of protocols for gene therapy.

Rescue of skeletal muscles of gamma-sarcoglycan-deficient mice with adeno-associated virus-mediated gene transfer.

In humans, a subset of cases of Limb-girdle muscular dystrophy (LGMD) arise from mutations in the genes encoding one of the sarcoglycan (alpha, beta, gamma, or delta) subunits of the dystrophin-glycoprotein complex. While adeno-associated virus (AAV) is a potential gene therapy vector for these dystrophies, it is unclear if AAV can be used if a diseased muscle is undergoing rapid degeneration and necrosis. The skeletal muscles of mice lacking gamma-sarcoglycan (gsg-/- mice) differ from the animal models that have been evaluated to date in that the severity of the skeletal muscle pathology is much greater and more representative of that of humans with muscular dystrophy. Following direct muscle injection of a recombinant AAV [in which human gamma-sarcoglycan expression is driven by a truncated muscle creatine kinase (MCK) promoter/enhancer], we observed significant numbers of muscle fibers expressing gamma-sarcoglycan and an overall improvement of the histologic pattern of dystrophy. However, these results could be achieved only if injections into the muscle were prior to the development of significant fibrosis in the muscle. The results presented in this report show promise for AAV gene therapy for LGMD, but underscore the need for intervention early in the time course of the disease process.

Differential requirement for individual sarcoglycans and dystrophin in the assembly and function of the dystrophin-glycoprotein complex.

Sarcoglycan is a multimeric, integral membrane glycoprotein complex that associates with dystrophin. Mutations in individual sarcoglycan subunits have been identified in inherited forms of muscular dystrophy. To evaluate the contributions of sarcoglycan and dystrophin to muscle membrane stability and muscular dystrophy, we compared muscle lacking specific sarcoglycans or dystrophin. Here we report that mice lacking (delta)-sarcoglycan developed muscular dystrophy and cardiomyopathy similar to mice lacking (gamma)-sarcoglycan. However, unlike muscle lacking (gamma)-sarcoglycan, (delta)-sarcoglycan-deficient muscle was sensitive to eccentric contraction-induced disruption of the plasma membrane. In the absence of (delta)-sarcoglycan, (alpha)-, (beta)- and (gamma)-sarcoglycan were undetectable, while dystrophin was expressed at normal levels. In contrast, without (gamma)-sarcoglycan, reduced levels of (alpha)-, (beta)- and (delta)-sarcoglycan were expressed, glycosylated and formed a complex with each other. Thus, the elimination of (gamma)- and (delta)-sarcoglycan had different molecular consequences for the assembly and function of the dystrophin-glycoprotein complex. Furthermore, these molecular differences were associated with different mechanical consequences for the muscle plasma membrane. Through this in vivo analysis, a model for sarcoglycan assembly is proposed.

Muscle degeneration without mechanical injury in sarcoglycan deficiency.

In humans, mutations in the genes encoding components of the dystrophin-glycoprotein complex cause muscular dystrophy. Specifically, primary mutations in the genes encoding alpha-, beta-, gamma-, and delta-sarcoglycan have been identified in humans with limb-girdle muscular dystrophy. Mice lacking gamma-sarcoglycan develop progressive muscular dystrophy similar to human muscular dystrophy. Without gamma-sarcoglycan, beta- and delta-sarcoglycan are unstable at the muscle membrane and alpha-sarcoglycan is severely reduced. The expression and localization of dystrophin, dystroglycan, and laminin-alpha2, a mechanical link between the actin cytoskeleton and the extracellular matrix, appears unaffected by the loss of sarcoglycan. We assessed the functional integrity of this mechanical link and found that isolated muscles lacking gamma-sarcoglycan showed normal resistance to mechanical strain induced by eccentric muscle contraction. Sarcoglycan-deficient muscles also showed normal peak isometric and tetanic force generation. Furthermore, there was no evidence for contraction-induced injury in mice lacking gamma-sarcoglycan that were subjected to an extended, rigorous exercise regimen. These data demonstrate that mechanical weakness and contraction-induced muscle injury are not required for muscle degeneration and the dystrophic process. Thus, a nonmechanical mechanism, perhaps involving some unknown signaling function, likely is responsible for muscular dystrophy where sarcoglycan is deficient.

Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice.

Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene, leading to the absence of the dystrophin protein in striated muscle. A significant number of these mutations are premature stop codons. On the basis of the observation that aminoglycoside treatment can suppress stop codons in cultured cells, we tested the effect of gentamicin on cultured muscle cells from the mdx mouse - an animal model for DMD that possesses a premature stop codon in the dystrophin gene. Exposure of mdx myotubes to gentamicin led to the expression and localization of dystrophin to the cell membrane. We then evaluated the effects of differing dosages of gentamicin on expression and functional protection of the muscles of mdx mice. We identified a treatment regimen that resulted in the presence of dystrophin in the cell membrane in all striated muscles examined and that provided functional protection against muscular injury. To our knowledge, our results are the first to demonstrate that aminoglycosides can suppress stop codons not only in vitro but also in vivo. Furthermore, these results raise the possibility of a novel treatment regimen for muscular dystrophy and other diseases caused by premature stop codon mutations. This treatment could prove effective in up to 15% of patients with DMD.

[Evaluation of esophageal motility disorders triggered by ingestion of solids in the case of non-obstructive dysphagia]. / Evaluation des anomalies motrices oesophagiennes déclenchées par l'ingestion de solides en cas de dysphagie non obstructive.

UNLABELLED: The aim of this study was to define the normal manometric pattern of esophageal motility in response to food ingestion and to evaluate the contribution of esophageal manometry in the management of patients complaining of functional dysphagia. PATIENTS AND METHODS: Twenty-one healthy volunteers and 25 consecutive patients complaining of functional dysphagia with normal conventional esophageal manometry were included in this prospective study. An event marker was used to study the relationship between dysphagia and motility events. RESULTS: Twenty-two out of 25 patients (88%) reported dysphagia during esophageal manometry with food ingestion, while none complained of dysphagia during conventional esophageal manometry. Significantly, food ingestion induced in healthy volunteers and in patients: an increase in the amplitude and duration of esophageal body peristaltic contractions, and a decrease in their propagation speed; an increase in the basal pressure and a decrease in the relaxation percentage of the lower esophageal sphincter during deglutition. The percentage of solid swallows with one or several of the 7 abnormal motility patterns studied prospectively was significantly higher among patients (53.7%) than among healthy volunteers (4.3%) (P < 0.0001); it was also significantly higher among patients during swallows with dysphagia (70.1%) than without dysphagia (33.6%) (P < 0.0001). CONCLUSION: Esophageal manometry with food ingestion is an effective means of defining abnormal motility patterns and their relationship with dysphagia during functional dysphagia.

Plasmodium berghei development in irradiated sporozoite-immunized C57BL6 mice.

The C57BL6 strain of mice is highly susceptible to Plasmodium berghei sporozoite infections and consequently requires repeated immunizations with irradiated sporozoites to obtain protective immunity. After a live sporozoite challenge in the immunized hosts, hepatic-stage parasites found in the liver after 48 h are of different sizes--small schizonts corresponding to blocked forms (derived from irradiated sporozoites), and schizonts of intermediate size (derived from live sporozoites). Large schizonts corresponding to mature hepatic forms are found only in unimmunized but challenged C57BL6 mice. Using monoclonal and polyclonal antibodies directed to liver-stage parasites, different patterns of binding reactivity to the above forms are observed. More than 20% of the irradiated sporozoites transform into blocked forms after immunization and persist in the liver. Upon sporozoite challenge in such immunized animals the rate of transformation of sporozoites into hepatic parasites is less than 2%. These observations shed light on the fate of live sporozoite development in irradiated sporozoite-immunized C57BL6 mice.

A case of myiasis in man due to Wohlfahrtia magnifica (Schiner) recorded near Rome.

In this report the case of a 14-year-old Italian boy is described in whom scratching wounds of the scalp were invaded by maggots of the dipterous Wohlfahrtia magnifica (Schiner).