Alpha heating of indirect-drive layered implosions on the National Ignition Facility.

In order to understand how close current layered implosions in indirect-drive inertial confinement fusion are to ignition, it is necessary to measure the level of alpha heating present. To this end, pairs of experiments were performed that consisted of a low-yield tritium-hydrogen-deuterium (THD) layered implosion and a high-yield deuterium-tritium (DT) layered implosion to validate experimentally current simulation-based methods of determining yield amplification. The THD capsules were designed to reduce simultaneously DT neutron yield (alpha heating) and maintain hydrodynamic similarity with the higher yield DT capsules. The ratio of the yields measured in these experiments then allowed the alpha heating level of the DT layered implosions to be determined. The level of alpha heating inferred is consistent with fits to simulations expressed in terms of experimentally measurable quantities and enables us to infer the level of alpha heating in recent high-performing implosions.

High-Performance Indirect-Drive Cryogenic Implosions at High Adiabat on the National Ignition Facility.

To reach the pressures and densities required for ignition, it may be necessary to develop an approach to design that makes it easier for simulations to guide experiments. Here, we report on a new short-pulse inertial confinement fusion platform that is specifically designed to be more predictable. The platform has demonstrated 99%+0.5% laser coupling into the hohlraum, high implosion velocity (411 km/s), high hotspot pressure (220+60 Gbar), and high cold fuel areal density compression ratio (>400), while maintaining controlled implosion symmetry, providing a promising new physics platform to study ignition physics.

Residual vein obstruction in patients diagnosed with acute isolated distal deep vein thrombosis associated with active cancer.

After acute proximal deep vein thrombosis (DVT) the thrombotic mass decreases, especially during the first months of anticoagulation. The persistence of residual vein obstruction (RVO) may predict future recurrence in patients with cancer-associated DVT. We aimed to evaluate the proportion of patients with RVO after an episode of cancer associated isolated distal DVT (IDDVT), to identify variables associated with RVO, and to provide initial evidence of its association with recurrent VTE. We performed a post-hoc analysis of a multicenter cohort study of patients with isolated cancer-associated acute IDDVT. We included patients who underwent a control ultrasonography at the end of the anticoagulant treatment between day 30 and day 365 after index IDDVT, given that no recurrent VTE had already occurred on anticoagulant treatment. A total of 153 patients had ultrasonographic follow-up after a median of 92 days from index IDDVT: 45.8% had RVO and 54.2% exhibited complete recanalization. Female sex, Body Mass Index > 30 Kg/m2 and involvement of axial calf veins showed the strongest association with RVO. The risk of recurrence was twofold higher in patients with (versus without) RVO. RVO persisted in approximately half of patients with an episode of cancer-associated IDDVT at anticoagulant discontinuation. Patients with RVO appeared to be at a higher risk for recurrent events.

Clinical course of isolated distal deep vein thrombosis in patients with active cancer: a multicenter cohort study.

Essentials Isolated distal deep vein thrombosis (IDDVT) is frequently associated with cancer. No study has specifically evaluated the long-term clinical course of cancer-associated IDDVT. Patients with cancer-associated IDDVT are at very high risk of symptomatic recurrence and death. We observed low rates of major bleeding during anticoagulation. SUMMARY: Background Although isolated distal deep vein thrombosis (IDDVT) is frequently associated with cancer, no study has specifically evaluated the long-term clinical course of IDDVT in this setting. Aim To provide data on the rate of recurrent venous thromboembolism (VTE), major bleeding events and death in IDDVT patients with active cancer. Patients and Methods Consecutive patients with active cancer and an objective IDDVT diagnosis (January 2011 to September 2014) were included from our files. We collected information on baseline characteristics, IDDVT location and extension, VTE risk factors, and type and duration of anticoagulant treatment. Results A total of 308 patients (mean age 66.2 [standard deviation (SD), 13.2 years]; 57.1% female) with symptomatic IDDVT and a solid (n = 261) or hematologic (n = 47) cancer were included at 13 centers. Cancer was metastatic in 148 (48.1%) patients. All but three (99.0%) patients received anticoagulant therapy, which consisted of low-molecular-weight heparin in 288 (93.5%) patients. Vitamin K antagonists were used for the long-term treatment in 46 (14.9%) patients, whereas all others continued the initial parenteral agent for a mean treatment duration of 4.2 months (SD, 4.6 months). During a total follow-up of 355.8 patient-years (mean, 13.9 months), there were 47 recurrent objectively diagnosed VTEs for an incidence rate of 13.2 events per 100 patient-years. During anticoagulant treatment, the annual incidence of major bleeding was 2.0 per 100 patient-years. Conclusions Cancer patients with IDDVT have a high risk of VTE recurrence. Additional studies are warranted to investigate the optimal intensity and duration of anticoagulant treatment for these patients.

OC-01 - Clinical history of cancer patients with isolated distal deep vein thrombosis: a multicenter cohort study.

INTRODUCTION: Isolated distal deep vein thrombosis (IDDVT) accounts for one-fourth to one-half of all deep vein thrombosis (DVT) of the leg. Patients with IDDVT are frequently treated for a shorter period of time compared to patients with proximal DVT and/or pulmonary embolism (PE) due to a perceived lower risk of recurrence. About 10-20% of patients with venous thromboembolic events (VTEs) have concomitant cancer. Guidelines recommend long-term anticoagulant treatment in this group of patients due to their high risk of VTE recurrence. Unfortunately, information on the clinical history of IDDVT patients is limited and, to date, no study has evaluated the long-term risk of VTE recurrence in IDDVT patients with cancer. AIM: To provide information on the clinical history of IDDVT patients with active cancer. MATERIALS AND METHODS: A multicenter, cohort study including active-cancer patients with an objective diagnosis of IDDVT (between January 2011 and September 2014) was conducted. Information on baseline characteristics, thrombosis location and extension, concomitant risk factors, type and duration of treatment was collected. All patients were followed for a minimum of 12 months and up to 24 months. During follow-up, VTE recurrence, major bleeding episodes and death were registered. Potential risk factors for VTE recurrence were evaluated. RESULTS: 308 patients (mean age 66.2±13.2 years, female 57.1%) in 13 centers were included, Table 1; 261 patients had solid cancer and 47 patients hematologic cancer. At the time of IDDVT diagnosis, the disease was metastatic in 148 patients (48.1%); 99.0% of patients received anticoagulant treatment: 288 patients (93.5%) were initially treated with low molecular weight heparin, 15 with fondaparinux (5.2%) and 1 with unfractionated heparin; vitamin K antagonists were used in 46 patients (14.9%) only. Total follow-up was 389 patient-years, mean follow-up 15.2 months. Mean duration of treatment was 4.2 months. During the study period there were 47 episodes of VTE recurrence (36 proximal DVT or PE) for a incidence rate of 13.2 events per 100 patient-years; 7 patients had major bleeding (2.3%) and 137 died (44.5%). At multivariate analysis, previous VTE was associated with an increased risk of recurrence (OR 2.10; 95% 1.06, 4.14), whereas patients with gastrointestinal cancer had a lower risk of recurrence (OR 0.26; 95% CI 0.08, 0.86). CONCLUSIONS: Cancer patients with IDDVT have a high risk of VTE recurrence. Other studies are warranted to address the adequate management of these patients.

Emergency reversal of anticoagulation with vitamin K antagonists with 3-factor prothrombin complex concentrates in patients with major bleeding.

Major bleeding is a serious and potentially fatal complication of treatment with vitamin K antagonists (VKAs). Prothrombin complex concentrates (PCCs) can substantially shorten the time needed to reverse VKA effects. To determine the efficacy and safety of 3-factor PCCs for the rapid reversal of VKAs in patients with major bleeding. Patients receiving VKAs and suffering from acute major bleeding were eligible for this prospective cohort study if their international normalized ratio (INR) was higher than or equal to 2.0. Stratified 35-50 IU kg(-1) PCC doses were infused based on initial INR. A total of 126 patients (62 males; mean age: 74 years, range 37-96 years) were enrolled. The mean INR at presentation was 3.3 (range 2-11). At 30 min after PCC administration the mean INR was 1.4 (range: 0.9-3.1), declining to less than or equal to 1.5 in 75 % of patients. The benefit of PCC was maintained for a long time, since in 97 % of all post-infusion time points through 96 h the mean INR remained lower than or equal to 1.5 (mean: 1.19; range: 0.9-2.3). During hospitalization neither thrombotic complications nor significant adverse events were observed and 12 patients died (10 %); none of the deaths was judged to be related to PCC administration. 3-factor PCC administration is an effective, rapid ad safe treatment for the urgent reversal of VKAs in patients with acute major bleeding. Broader use of PCC in this clinical setting appears to be appropriate.

Psidium guajava L. anti-neoplastic effects: induction of apoptosis and cell differentiation.

OBJECTIVES: Curative properties of medicinal plants such as Psidium guajava L. (Myrtaceae) have often been indicated by epidemiological studies on populations in which these fruits are consumed daily. However, complete characterization of the active principles responsible for this ability has never been performed. Here, we have characterized P. guajava's anti-cancer potential and identified the parts of the fruit involved in its anti-neoplastic action. MATERIALS AND METHODS: We studied morphology of our cells, cell cycle characteristics and apoptosis and performed immunostaining, differentiation and western blot analyses. RESULTS: We report that the P. guajava extract exerted anti-cancer control on both haematological and solid neoplasias. P. guajava extract's anti-tumour properties were found to be tightly bound to induction of apoptosis and differentiation. Use of ex vivo myeloid leukaemia blasts corroborated that P. guajava was able to induce cell death but did not exhibit anti-cancer effects on all malignant cells investigated, indicating selective activity against certain types of tumour. Analyses of P. guajava pulp, peel and seeds identified the pulp as being the most relevant component for causing cell cycle arrest and apoptosis, whereas peel was responsible for causing cell differentiation. P. guajava itself and its pulp-derived extract were found to induce apoptosis accompanied by caspase activation and p16, p21, Fas ligand (FASL TNF super-family, member 6), Bcl-2-associated agonist of cell death (BAD) and tumour necrosis factor receptor super-family, member 10b (DR5), overexpression. CONCLUSIONS: Our findings showed that P. guajava L. extract was able to exert anti-cancer activity on cultures in vitro and ex vivo, supporting the hypothesis of its anti malignant pro-apoptotic modulation.

Avian influenza surveillance in backyard poultry of Argentina.

Avian influenza (AI) is an exotic disease in Argentina. A surveillance program for AI was conducted in backyard poultry during 1998-2005 in two regions: 1) region A, which included the avian population in the provinces that border Brazil, Bolivia, and Paraguay, and 2) region B, which included the rest of the provinces of the country. More than 8000 serum samples were tested for antibodies by enzyme-linked immunosorbent assay and/or agar gel immunodiffusion tests, and more than 18,000 tracheal and cloacal swabs were tested for virus by isolation in embryonated specific-pathogen-free eggs. This study was part of the AI prevention program in Argentina, which includes other avian populations such as commercial poultry and all the controls for importation and exportation of live birds. The results from backyard poultry were negative for AI.

Genetic variability among flavescence dorée phytoplasmas from different origins in Italy and France.

Flavescence dorée is a devastating disease of grapevine widespread in several countries in EU such as France, Italy and Spain. Genetic variability among 17 Italian and 3 French FD strains was investigated by RFLP analyses based on a fragment of the ribosomal protein operon and on the non-ribosomal DNA fragment FD9. RFLP analysis of the PCR amplified ribosomal protein fragment, coding for the 3' end of rpl22 and the entire rps3 genes, differentiated 4 rp-subgroups among the FD strains and 4 subgroups among the reference strains belonging to elm yellows group (16SrV). Sequencing and phylogenetic analysis of the same ribosomal protein DNA fragment validated the delineation of 4 distinct FD strain types derived by RFLP analyses. The results supported the differentiation based on analysis of the non-ribosomal DNA fragment FD9. The phylogenetic analysis further revealed relationships and a probable evolutionary trend among the FD strains and the other representatives of elm yellows group. All the FD strains together with the reference strains ALY, RuS and JWB formed a cluster very well distinct from the EY/ULW cluster. Moreover, ALY was shown to be more closely related to three FD strain types: the Lombardia/Piemonte, the French FD70, and the French FD88/Italian FD-D strain clusters.

Vaccine therapy of B cell malignancies: different strategies for a novel approach.

This review deals with the theoretical principles and experimental results of immunotherapy for B cell malignancies, namely for non-Hodgkin lymphomas (NHLs) and multiple myeloma. Its focus is the use of vaccines in clinical practice with particular emphasis on the most recent developments and therapeutic opportunities arising from combination therapies. Previous studies will be reviewed and the present status of vaccine technology summarized.

Defective antifungal T-helper 1 (TH1) immunity in a murine model of allogeneic T-cell-depleted bone marrow transplantation and its restoration by treatment with TH2 cytokine antagonists.

Patients undergoing full haplotype-mismatched hematopoietic transplantations may experience severe intractable invasive fungal infections. To verify whether an imbalanced production of T-helper 1 (TH1) and TH2 cytokines may be responsible for susceptibility to fungal infections, C3H/HeJ (H-2(k)) recipient mice were lethally irradiated, received transplantations with T-cell-depleted allogeneic bone marrow (BM) cells from mice of H-2(d) haplotype, and were infected with Candida albicans. At different time-points after transplantation, mice were assessed for pattern of TH cytokine production and susceptibility to infection. The results show that a long-term, donor-type chimerism was achieved as early as 2 weeks after BM transplantation (BMT), at the time when high-level production of TH2 cytokines (interleukin-4 [IL-4] and IL-10) and impaired production of TH1 cytokines (interferon-gamma [IFN-gamma] and IL-12] were observed. At this time, mice were highly susceptible to both disseminated and mucosal infections, as indicated by decreased survival, uncontrolled fungal growth, and failure to develop protective TH1 immunity. However, a predominant production of TH1 cytokines was observed by week 5 after BMT, at the time when mice developed donor-type protective TH1 responses and were resistant to infections. Therapeutic ablation of IL-4 or IL-10 greatly increased resistance to candidiasis. These results indicate that a dysregulated production of TH cytokines occurs in mice undergoing T-cell-depleted allogeneic BMT. The transient predominant production of TH2 cytokines over that of IL-12 impaired the ability of mice to develop antifungal TH1 resistance, an activity that could be efficiently restored upon treatment with TH2 cytokine antagonists.

Incidental parathyroid adenomas with normocalcemia discovered during thyroid operations: report of three cases.

We report three cases of parathyroid adenoma incidentally discovered during a total thyroidectomy. No patients showed any clinical or chemical features that led us to suspect a hyperparathyroidism condition before operation, but a macroscopically enlarged parathyroid was discovered during the dissection and it was removed in all three cases. All patients had a single adenoma confirmed by a histological analysis. Calcemia decreased after operation in every case but only one patient needed temporary adjunctive therapy. No permanent hypoparathyroidism or recurrent hyperparathyroidism was observed. We recommend that any enlarged parathyroid discovered during neck surgery should thus be removed in order to avoid the risks of future surgical procedures due to successive bouts of clinical hyperparathyroidism.

In vivo demethylation of a MoMuLV retroviral vector expressing the herpes simplex thymidine kinase suicide gene by 5' azacytidine.

We constructed a functional MoMuLV-based bicistronic retroviral vector encoding the herpes simplex virus type I thymidine kinase gene, which induces sensitivity to the prodrug ganciclovir (gcv), and the reporter beta-galactosidase gene (MFG-tk-IRES-lacZ). The U937 histiocytic cell line was transduced with this vector, and a clone (VB71) with high-level transgene expression was selected. Severe combined immunodeficient (SCID) mice were injected with VB71 cells to evaluate the role of long terminal repeat methylation in transgene silencing in vivo and to see whether 5-azacytidine (5' aza-C) demethylating agent prevented it. We found 5' aza-C maintained gene expression at high level in vitro. In vivo, time to tumor onset was significantly longer in SCID mice receiving the VB71 cells, 5' aza-C, and gcv compared with animals treated with either 5' aza-C or gcv alone. The number of injected tumor cells influences tumor onset time and the efficacy of 5' aza-C and gcv treatment. The standard gcv treatment schedule (10 mg/kg from d + 1 until the onset of tumor) controlled tumor onset better than short-term treatment with high doses. In conclusion, the results extend our previous findings that transgene methylation in vivo may be prevented with an appropriate schedule of 5' aza-C and gcv.

Familial papillary carcinoma of the thyroid: a report of nine first-degree relatives of four families.

The authors report the occurrence of papillary carcinoma of the thyroid in nine first-degree relatives of four families among a consecutive series of 97 patients with papillary carcinoma of the thyroid who were operated on from 1991 to 1998. Total thyroidectomy was performed in all cases. All patients are alive without evidence of disease after a mean follow-up period of 43 months. Since in our series familial papillary carcinoma of the thyroid was found in 9.3% of patients, we suggest an adequate screening among first-degree relatives of all patients with papillary thyroid carcinoma. Because of reported aggressive behaviour of familial papillary carcinoma of the thyroid, aggressive surgical treatment plus post-operative thyroid remnant ablation with radio-iodine should be warranted in all patients.

Changes in HDL-cholesterol and lipoprotein Lp(a) after 6-month treatment with finasteride in males affected by benign prostatic hyperplasia (BPH).

Androgen effects on lipoproteins, mainly high density lipoprotein (HDL), could be exerted by a direct interaction of testosterone (T) or dihydrotestosterone (DHT) with liver androgen receptors. To assess if T needs to be converted into DHT to affect lipid metabolism, 13 patients were studied, affected with benign prostatic hyperplasia (BPH) and treated with an inhibitor of 5 alpha-reductase (finasteride). They were compared with 15 untreated controls. At baseline and after 3 and 6 months of therapy, each patient was evaluated as for lipoprotein and hormone concentrations, as well as for nutritional status. Body composition was assessed by anthropometry and bio-impedance analysis (BIA). Treatment was associated with a significant increase of HDL-cholesterol (HDL-C), mainly HDL3 subclass, and lipoprotein(a) (Lp(a)), as well as a decline of DHT, whereas no significant changes were apparent for T, estradiol (E2), sex hormone binding hormone (SHBG) and body composition indexes. However, no significant associations between DHT and lipid relative changes were apparent at bivariate correlation analysis. This finding was confirmed by comparing patient subsets identified by cluster analysis, according to HDL subclass individual responses. Rather, a slight association with E2 for HDL2 (positive) and HDL3 (negative) was found. In conclusion, finasteride can modify HDL and Lp(a) concentrations. However, by the data, these effects cannot be definitively attributed to the changes in DHT synthesis induced by finasteride, since a direct and non-specific interference of the drug on liver metabolism cannot be excluded.

Análisis de un brote de diarrea aguda / Analysis of an outbreak of an acute diarrhoea

Durante los meses de mayo a julio de 1998, se presentaron en la localidad de Río Pico, de la Provincia del Chubut, un número significativamente elevado de pacientes con enfermedad diarreica y síntomas sistémicos. Se realizó un trabajo con los profesionales del Hospital Rural de Río Pico, del Hospital Zonal de Esquel, del Area Prográmatica Zona Noroeste del Chubut y del Departamento Zonal de Medio Ambiente del Chubut ante la sospecha de la existencia de un brote de disentería. Se elaboró una ficha donde se registraron datos de 82 de los 120 casos notificados que permitiera establecer el patrón epidemiológico del brote. Se practicaron coprocultivos de casos índices, se hizo búsqueda de portación de manipuladores de alimentos y se tomaron muestras de agua de la localidad. Se identificó como agente etiólogico Shigella Sonnei. El análisis de estas variables condujo a tomar medidas que incluyeron la suspensión de las actividades escolares, tratamiento precoz con antimicrobianos y difusión por los medios de prensa locales de medidas higiénico-dietéticas. Estas medidas fueron dirigidas a controlar la transmisión persona a persona principal mecanismo involucrado en la diseminación de las disentería bacilares. Con su implementación disminuyó significativamnente la frecuencia de los casos. El presente trabajo tiene como objetivo alertar sobre la necesidad de implementar correctamente los mecanismos de vigilancia y mostrar una forma de analizar un brote adaptando el estudio al terreno

Análisis de un brote de diarrea aguda / Analysis of an outbreak of an acute diarrhoea

Durante los meses de mayo a julio de 1998, se presentaron en la localidad de Río Pico, de la Provincia del Chubut, un número significativamente elevado de pacientes con enfermedad diarreica y síntomas sistémicos. Se realizó un trabajo con los profesionales del Hospital Rural de Río Pico, del Hospital Zonal de Esquel, del Area Prográmatica Zona Noroeste del Chubut y del Departamento Zonal de Medio Ambiente del Chubut ante la sospecha de la existencia de un brote de disentería. Se elaboró una ficha donde se registraron datos de 82 de los 120 casos notificados que permitiera establecer el patrón epidemiológico del brote. Se practicaron coprocultivos de casos índices, se hizo búsqueda de portación de manipuladores de alimentos y se tomaron muestras de agua de la localidad. Se identificó como agente etiólogico Shigella Sonnei. El análisis de estas variables condujo a tomar medidas que incluyeron la suspensión de las actividades escolares, tratamiento precoz con antimicrobianos y difusión por los medios de prensa locales de medidas higiénico-dietéticas. Estas medidas fueron dirigidas a controlar la transmisión persona a persona principal mecanismo involucrado en la diseminación de las disentería bacilares. Con su implementación disminuyó significativamnente la frecuencia de los casos. El presente trabajo tiene como objetivo alertar sobre la necesidad de implementar correctamente los mecanismos de vigilancia y mostrar una forma de analizar un brote adaptando el estudio al terreno (AU)

[The inferior nonrecurrent laryngeal nerve: a report of 7 cases observed since 1987]. / Il nervo laringeo inferiore non ricorrente: descrizione di 7 casi osservati dal 1987.

The non-recurrent inferior laryngeal nerve is a rare anomaly (0.34% on th right side, extremely rare on the left side) that increases the risk of damage to the nerve during thyroid and parathyroid surgery. Seven cases of non-recurrent laryngeal nerve are reported, emphasizing the diagnostic accuracy of angio-MR for the anatomical identification of the vascular anomaly that invariably occurs with the nerve malformation.

Aging-related decline of gonadal function in healthy men: correlation with body composition and lipoproteins.

OBJECTIVE: To assess if androgen decline in physiological aging contributes to the concomitant changes in body composition and lipoprotein levels. DESIGN: Cross-sectional, observational study. SETTING: A university-based outpatient center. SUBJECTS: The study comprised 206 healthy volunteers (aged 18-95 years). MEASUREMENTS: Blood samples were drawn after an overnight fast for the assay of hormones (free testosterone (FT), estradiol (E2), and sex hormone-binding globulin (SHBG)) and lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol, and lipoprotein Lp(a)). At the same time, body composition was assessed by both anthropometry (fat mass percentage (FM%) estimated from four measures of skinfold thickness using the Durnin and Womersley equation and the Siri equation) and by bioimpedance analysis (FM% estimated using the Segal or Deurenberg equations, respectively, for subjects younger or older than 62 years). RESULTS: A significant age-related decline was found for FT and E2 concentrations, whereas SHBG levels were related positively with age. No significant association was apparent between hormonal changes and the concomitant modifications of body composition and lipoproteins. Only SHBG showed a significant inverse association between FM% and the waist-to-hip ratio, independent of age. The comparison between older hypogonadal (with FT levels below the lower limit of the normality range assessed in younger subjects) and eugonadal men did not show any significant differences in body composition or lipid profile. CONCLUSIONS: This study suggests that, in men, androgen decline caused by normal aging does not significantly affect some targets of testosterone action, such as body composition and lipid metabolism. Therefore, androgen supplementation in hypogonadal older men cannot be expected to influence nutritional status and body composition to the same extent that it does other main targets of testosterone action, such as sexual activity and muscle strength. However, we cannot exclude that selected subsets of older patients with low testosterone levels, especially if affected by catabolic disease, could benefit from the effects of androgen administration on nutritional status.