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We describe an analysis comparing the pp[over ¯] elastic cross section as measured by the D0 Collaboration at a center-of-mass energy of 1.96 TeV to that in pp collisions as measured by the TOTEM Collaboration at 2.76, 7, 8, and 13 TeV using a model-independent approach. The TOTEM cross sections, extrapolated to a center-of-mass energy of sqrt[s]=1.96 TeV, are compared with the D0 measurement in the region of the diffractive minimum and the second maximum of the pp cross section. The two data sets disagree at the 3.4σ level and thus provide evidence for the t-channel exchange of a colorless, C-odd gluonic compound, also known as the odderon. We combine these results with a TOTEM analysis of the same C-odd exchange based on the total cross section and the ratio of the real to imaginary parts of the forward elastic strong interaction scattering amplitude in pp scattering for which the significance is between 3.4σ and 4.6σ. The combined significance is larger than 5σ and is interpreted as the first observation of the exchange of a colorless, C-odd gluonic compound.
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BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive, high-grade, cutaneous neuroendocrine tumour (NET). Agents blocking programmed death 1/programmed death ligand 1 have efficacy in metastatic MCC (mMCC), but half of patients do not derive durable benefit. Somatostatin analogues (SSAs) are commonly used to treat low- and moderate-grade NETs that express somatostatin receptors (SSTRs). OBJECTIVES: To assess SSTR expression and the efficacy of SSAs in mMCC, a high-grade NET. Methods In this retrospective study of 40 patients with mMCC, SSTR expression was assessed radiologically by somatostatin receptor scintigraphy (SRS; n = 39) and/or immunohistochemically when feasible (n = 9). Nineteen patients (18 had SRS uptake in MCC tumours) were treated with SSA. Disease control was defined as progression-free survival (PFS) of ≥ 120 days after initiation of SSA. RESULTS: Thirty-three of 39 patients (85%) had some degree (low 52%, moderate 23%, high 10%) of SRS uptake. Of 19 patients treated with SSA, seven had a response-evaluable target lesion; three of these seven patients (43%) experienced disease control, with a median PFS of 237 days (range 152-358). Twelve of 19 patients did not have a response-evaluable lesion due to antecedent radiation; five of these 12 (42%) experienced disease control (median PFS of 429 days, range 143-1757). The degree of SSTR expression (determined by SRS and/or immunohistochemistry) did not correlate significantly with the efficacy endpoints. CONCLUSIONS: In contrast to other high-grade NETs, mMCC tumours appear frequently to express SSTRs. SSAs can lead to clinically meaningful disease control with minimal side-effects. Targeting of SSTRs using SSA or other novel approaches should be explored further for mMCC.
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Carcinoma de Células de Merkel , Neoplasias Cutáneas , Carcinoma de Células de Merkel/tratamiento farmacológico , Humanos , Receptores de Somatostatina , Estudios Retrospectivos , Neoplasias Cutáneas/tratamiento farmacológico , Somatostatina/uso terapéuticoRESUMEN
BACKGROUND: Interleukin 12 (IL-12) is a pivotal regulator of innate and adaptive immunity. We conducted a prospective open-label, phase II clinical trial of electroporated plasmid IL-12 in advanced melanoma patients (NCT01502293). PATIENTS AND METHODS: Patients with stage III/IV melanoma were treated intratumorally with plasmid encoding IL-12 (tavokinogene telseplasmid; tavo), 0.5 mg/ml followed by electroporation (six pulses, 1500 V/cm) on days 1, 5, and 8 every 90 days in the main study and additional patients were treated in two alternative schedule exploration cohorts. Correlative analyses for programmed death-ligand 1 (PD-L1), flow cytometry to assess changes in immune cell subsets, and analysis of immune-related gene expression were carried out on pre- and post-treatment samples from study patients, as well as from additional patients treated during exploration of additional dosing schedules beyond the pre-specified protocol dosing schedule. Response was measured by study-specific criteria to maximize detection of latent and potentially transient immune responses in patients with multiple skin lesions and toxicities were graded by the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). RESULTS: The objective overall response rate was 35.7% in the main study (29.8% in all cohorts), with a complete response rate of 17.9% (10.6% in all cohorts). The median progression-free survival in the main study was 3.7 months while the median overall survival was not reached at a median follow up of 29.7 months. A total of 46% of patients in all cohorts with uninjected lesions experienced regression of at least one of these lesions and 25% had a net regression of all untreated lesions. Transcriptomic and immunohistochemistry analysis showed that immune activation and co-stimulatory transcripts were up-regulated but there was also increased adaptive immune resistance. CONCLUSIONS: Intratumoral Tavo was well tolerated and led to systemic immune responses in advanced melanoma patients. While tumor regression and increased immune infiltration were observed in treated as well as untreated/distal lesions, adaptive immune resistance limited the response.
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Interleucina-12 , Melanoma , Neoplasias Cutáneas , Electroporación , Humanos , Inmunidad , Interleucina-12/uso terapéutico , Melanoma/tratamiento farmacológico , Melanoma/genética , Plásmidos , Estudios Prospectivos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/genéticaRESUMEN
Equine influenza (EI) is an important viral respiratory disease of equines caused by influenza A virus (IAV). The antigenic drift in IAVs necessitates regular updating and harmonization of vaccine strain with the circulating virus. The reverse genetics-based recombinant viruses could be easy instrument in generating vaccine against circulating virus in a quick and effective manner. Present study has been envisaged to evaluate the immunogenicity and protective efficacy of inactivated recombinant equine influenza virus (rgEIV) vaccine candidate having six segments from H1N1 virus (A/WSN/33/H1N1) and HA (hemaglutinin) and NA (neuraminidase) segments from H3N8 equine influenza virus [(A/eq/Jammu-Katra/06/08) of clade 2 of Florida sublineage] generated through reverse genetic engineering. BALB/c mice were immunized with inactivated rgEIV adjuvanted with aluminium hydroxide gel and challenged with H3N8 virus (A/eq/Jammu-Katra/06/08). The protective efficacy was evaluated through serology, cytokine profiling, clinical signs, gross and histopathological changes, immunohistochemistry and residual virus quantification. Immunizations induced robust humoral immune response as estimated through hemagglutination inhibition assay (HAI). The antibodies were isotyped and the predominant subclass was IgG1. The vaccine candidate produced mixed Th1 and Th2 responses through stimulation of IFN-γ, IL-2, IL-4 and IL-6 expression. Immunization protected mice against challenge as reflected through reduction in clinical signs and body weight loss, early recovery, mild pathological changes (gross and histopathological lesions) as evident through scoring of lesions, low residual virus in nasopharynx and lungs quantified through egg titration and quantitative reverse transcriptase PCR (qRT-PCR). The study demonstrates that inactivated recombinant EIV generated through reverse genetic approach provides equivalent protection to that observed with inactivated whole H3N8 EIV vaccine. Keywords: equine influenza; reverse genetics; vaccine; pathology; murine model.
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Subtipo H1N1 del Virus de la Influenza A , Subtipo H3N8 del Virus de la Influenza A , Vacunas contra la Influenza/inmunología , Infecciones por Orthomyxoviridae , Genética Inversa , Animales , Anticuerpos Antivirales , Modelos Animales de Enfermedad , Enfermedades de los Caballos/prevención & control , Caballos , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H3N8 del Virus de la Influenza A/genética , Vacunas contra la Influenza/genética , Ratones , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/prevención & controlRESUMEN
BACKGROUND: With increasing anti-PD-1 therapy use in patients with melanoma and other tumor types, there is interest in developing early on-treatment biomarkers that correlate with long-term patient outcome. An understanding of the pathologic features of immune-mediated tumor regression is key in this endeavor. MATERIALS AND METHODS: Histologic features of immune-related pathologic response (irPR) following anti-PD-1 therapy were identified on hematoxylin and eosin (H&E)-stained slides in a discovery cohort of pre- and on-treatment specimens from n = 16 patients with advanced melanoma. These features were used to generate an irPR score [from 0 = no irPR features to 3 = major pathologic response on biopsy (MPRbx, ≤10% residual viable tumor)]. This scoring system was then tested for an association with objective response by RECIST1.1 and overall survival in a prospectively collected validation cohort of pre- and on-treatment biopsies (n = 51 on-treatment at 4-week timepoint) from melanoma patients enrolled on the nivolumab monotherapy arm of CA209-038 (NCT01621490). RESULTS: Specimens from responders in the discovery cohort had features of immune-activation (moderate-high TIL densities, plasma cells) and wound-healing/tissue repair (neovascularization, proliferative fibrosis) compared to nonresponders, (P ≤ 0.021, for each feature). In the validation cohort, increasing irPR score associated with objective response (P = 0.009) and MPRbx associated with increased overall survival (n = 51; HR 0.13; 95%CI, 0.054-0.31, P = 0.015). Neither tumoral necrosis nor pretreatment histologic features were associated with response. Eight of 16 (50%) of patients with stable disease showed irPR features, two of which were MPRbx, indicating a disconnect between pathologic and radiographic features at the 4-week on-therapy timepoint for some patients. CONCLUSIONS: Features of immune-mediated tumor regression on routine H&E-stained biopsy slides from patients with advanced melanoma correlate with objective response to anti-PD-1 and overall survival. An on-therapy biopsy may be particularly clinically useful for informing treatment decisions in patients with radiographic stable disease. This approach is inexpensive, straightforward, and widely available.
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Antineoplásicos Inmunológicos/uso terapéutico , Biomarcadores de Tumor/análisis , Melanoma/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Neoplasias Cutáneas/tratamiento farmacológico , Piel/patología , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/farmacología , Biopsia , Femenino , Humanos , Ipilimumab/farmacología , Ipilimumab/uso terapéutico , Estimación de Kaplan-Meier , Masculino , Melanoma/inmunología , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Neoplasia Residual , Nivolumab/farmacología , Nivolumab/uso terapéutico , Receptor de Muerte Celular Programada 1/inmunología , Estudios Prospectivos , Criterios de Evaluación de Respuesta en Tumores Sólidos , Piel/efectos de los fármacos , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: Despite the completion of numerous phase II studies, a standard of care treatment has yet to be defined for metastatic uveal melanoma (mUM). To determine benchmarks of progression free survival (PFS) and overall survival (OS), we carried out a meta-analysis using individual patient level trial data. METHODS: Individual patient variables and survival outcomes were requested from 29 trials published from 2000 to 2016. Univariable and multivariable analysis were carried out for prognostic factors. The variability between trial arms and between therapeutic agents on PFS and OS was investigated. RESULTS: OS data were available for 912 patients. The median PFS was 3.3 months (95% CI 2.9-3.6) and 6-month PFS rate was 27% (95% CI 24-30). Univariable analysis showed male sex, elevated (i.e. > versus ≤ upper limit of normal) lactate dehydrogenase (LDH), elevated alkaline phosphatase (ALP) and diameter of the largest liver metastasis (≥3 cm versus <3 cm) to be substantially associated with shorter PFS. Multivariable analysis showed male sex, elevated LDH and elevated ALP were substantially associated with shorter PFS. The most substantial factors associated with 6-month PFS rate, on both univariable and multivariable analysis were elevated LDH and ALP. The median OS was 10.2 months (95% CI 9.5-11.0) and 1 year OS was 43% (95% CI 40-47). The most substantial prognostic factors for shorter OS by univariable and multivariable analysis were elevated LDH and elevated ALP. Patients treated with liver directed treatments had statistically significant longer PFS and OS. CONCLUSION: Benchmarks of 6-month PFS and 1-year OS rates were determined accounting for prognostic factors. These may be used to facilitate future trial design and stratification in mUM.
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Ensayos Clínicos como Asunto/normas , Neoplasias Hepáticas/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Proyectos de Investigación/estadística & datos numéricos , Neoplasias de la Úvea/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Fosfatasa Alcalina/sangre , Benchmarking , Conjuntos de Datos como Asunto , Femenino , Humanos , Estimación de Kaplan-Meier , L-Lactato Deshidrogenasa/sangre , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Melanoma/sangre , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Pronóstico , Supervivencia sin Progresión , Estudios Prospectivos , Factores Sexuales , Factores de Tiempo , Neoplasias de la Úvea/sangre , Neoplasias de la Úvea/mortalidad , Neoplasias de la Úvea/patología , Adulto JovenRESUMEN
The management of pain during root canal treatment is important. The aim of this systematic review and network meta-analysis was to identify the anaesthetic solution that would provide the best pulpal anaesthesia for inferior alveolar nerve blocks (IANB) treating mandibular teeth with irreversible pulpitis. Two electronic databases (PubMed and Scopus) were searched to identify studies up to October 2018. Randomized clinical trials comparing at least two anaesthetic solutions (lidocaine (lignocaine), articaine, bupivacaine, prilocaine or mepivacaine) used for IANB for treatment of irreversible pulpitis were included. The revised Cochrane risk of bias tool for randomized trials was used to assess the quality of the included studies. Pairwise meta-analysis, network meta-analysis using a random-effects model, and SUCRA ranking were performed. The network meta-analysis estimated the probability of each treatment performing best. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach. In total, 11 studies (n = 750) were included in the meta-analysis. The network meta-analysis revealed that only mepivacaine significantly increased the success rate of IANB compared to lidocaine (RR, 1.42 [95% CI 1.04-1.95]). However, no significant differences in the success rate of IANB were observed between mepivacaine and other anaesthetic agents (articaine and bupivacaine). Of all anaesthetic agents, mepivacaine (SUCRA = 0.81) ranked first in increasing the success rate of IANB, followed by prilocaine (SUCRA = 0.62), articaine (SUCRA = 0.54), bupivacaine (SUCRA = 0.41) and lidocaine (SUCRA = 0.13). The overall quality of evidence was very low to moderate. In conclusion, based on the evidence from the randomized clinical trials included in this review, mepivacaine with epinephrine demonstrated the highest probability of providing effective pulpal anaesthesia using IANB for teeth with irreversible pulpitis compared to prilocaine, articaine, bupivacaine and lidocaine. Further, high-quality clinical trials are needed to support the conclusion of this review.
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Anestesia Dental , Bloqueo Nervioso , Pulpitis , Anestésicos Locales , Método Doble Ciego , Humanos , Lidocaína , Nervio Mandibular , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: In Western Himalayas, Indian Army soldiers take 11 days (6 days of acclimatization and 5 days of travel) on a sea-level to high altitude road (SH road) to reach a high altitude location (HAL) situated at an altitude of 11,500 feet from sea-level location (SLL) at an altitude of 1150 feet while following acclimatization schedule (AS). AS has an extra safety margin over the conventional 'mountaineering thumb rule' of not exceeding 500 m sleeping altitude above 3000 m altitude. We carried out this randomised field trial to study the feasibility of moving large number of troops rapidly from SLL to HAL on SH road in western Himalayas in 4 days under pharmaco-prophylaxis. METHODS: Based on the pharmaco-prophylaxis, at SLL 508 healthy lowland soldiers were divided into two groups: 'A' (n = 256) with Acetazolamide + Dexamethasone and 'B' (n = 252) with Acetazolamide + Placebo. They travelled rapidly by road to HAL in 4 days and prevalence of acute mountain sickness (AMS), high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE) during the ascent was measured. RESULTS: Prevalence of AMS was found to be 1.56% and 1.59% in group 'A' and group 'B' respectively during the ascent with no cases of HAPE and HACE. CONCLUSION: At least on SH road, troops can be inducted rapidly to HAL from SLL in 4 days under pharmaco-prophylaxis with Acetazolamide with minimal occurrence of acute high altitude illnesses.
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We present a measurement of the effective weak mixing angle parameter sin^{2}θ_{eff}^{â} in pp[over ¯]âZ/γ^{*}âµ^{+}µ^{-} events at a center-of-mass energy of 1.96 TeV, collected by the D0 detector at the Fermilab Tevatron Collider and corresponding to 8.6 fb^{-1} of integrated luminosity. The measured value of sin^{2}θ_{eff}^{â}[µµ]=0.23016±0.00064 is further combined with the result from the D0 measurement in pp[over ¯]âZ/γ^{*}âe^{+}e^{-} events, resulting in sin^{2}θ_{eff}^{â}[comb]=0.23095±0.00040. This combined result is the most precise measurement from a single experiment at a hadron collider and is the most precise determination using the coupling of the Z/γ^{*} to light quarks.
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BACKGROUND: In the view of endemic avian influenza H9N2 infection in poultry, its zoonotic potential and emergence of antiviral resistance, two herbal plants, Ocimum sanctum and Acacia arabica, which are easily available throughout various geographical locations in India were taken up to study their antiviral activity against H9N2 virus. We evaluated antiviral efficacy of three different extracts each from leaves of O. sanctum (crude extract, terpenoid and polyphenol) and A. arabica (crude extract, flavonoid and polyphenol) against H9N2 virus using in ovo model. METHODS: The antiviral efficacy of different leaves extracts was systematically studied in three experimental protocols viz. virucidal (dose-dependent), therapeutic (time-dependent) and prophylactic (dose-dependent) activity employing in ovo model. The maximum non-toxic concentration of each herbal extracts of O. sanctum and A. arabica in the specific pathogen free embryonated chicken eggs was estimated and their antiviral efficacy was determined in terms of reduction in viral titres, measured by Haemagglutination (HA) and real time quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays. RESULTS: All the extracts of O. sanctum (crude extract, terpenoid and polyphenol) and A. arabica (crude extract, flavonoid and polyphenol) showed significant virucidal activity, however, crude extract ocimum and terpenoid ocimum showed highly significant to significant (p < 0.001-0.01) decrease in virus genome copy numbers with lowest dose tested. Similarly, therapeutic effect was observed in all three extracts of O. sanctum in comparison to the virus control, nevertheless, crude extract ocimum and terpenoid ocimum maintained this effect for longer period of time (up to 72 h post-incubation). None of the leaves extracts of A. arabica had therapeutic effect at 24 and 48 h post-incubation, however, only the crude extract acacia and polyphenol acacia showed delayed therapeutic effect (72 h post-inoculation). Prophylactic potential was observed in polyphenol acacia with highly significant antiviral activity compared to virus control (p < 0.001). CONCLUSIONS: The crude extract and terpenoid isolated from the leaves of O. sanctum and polyphenol from A. arabica has shown promising antiviral properties against H9N2 virus. Future investigations are necessary to formulate combinations of these compounds for the broader antiviral activity against H9N2 viruses and evaluate them in chickens.
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Acacia/química , Antivirales , Subtipo H9N2 del Virus de la Influenza A/efectos de los fármacos , Ocimum sanctum/química , Extractos Vegetales , Animales , Antivirales/química , Antivirales/farmacología , Antivirales/toxicidad , Embrión de Pollo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/toxicidad , Hojas de la Planta/química , Reacción en Cadena en Tiempo Real de la Polimerasa , Replicación Viral/efectos de los fármacosRESUMEN
An inactivated vaccine was developed using the rgH5N2 virus (6 + 2 reassortant) generated by plasmid based reverse genetics system (RGS) with WSN/33/H1N1 as backbone virus. Following mutation of the basic amino acid cleavage site RRRKKR*GLF to IETR*GLF, the H5-HA (haemagglutinin) gene of the selected donor H5N1 virus (A/chicken/West Bengal/80995/2008) of antigenic clade 2.2 was used along with the N2-NA gene from H9N2 field isolate (A/chicken/Uttar Pradesh/2543/2004) for generation of the rgH5N2 virus. A single dose (0.5 ml/bird) of the inactivated rgH5N2 vaccine protected 100% of the vaccinated chickens (n = 10) on 28(th) dpv (early challenge) and 90% of the vaccinated chickens (n = 10) on 200(th) dpv (late challenge) against high dose challenge with HPAI virus (10(9) EID50/bird). Challenge virus shedding via oropharynx and cloaca of the vaccinated chickens was detectable by realtime RT-PCR during 1-5 dpc and 1-9 days dpc in the early and the late challenge, respectively. The protective level of antibodies (mean HI titre > 128) was maintained without booster vaccination for 200 days. The present study provides the experimental evidence about the extent of protection provided by a reverse genetics based vaccine for clade 2.2 H5N1 viruses against challenge with high dose of field virus at two different time points (28 dpv and 200 dpv). The challenge study is uniquely different from the previous similar experiments on account of 1000 times higher dose of challenge and protection at 200 dpv. The protection and virus shedding data of the study may be useful for countries planning to use H5 vaccine in poultry especially against the clade 2.2 H5N1 viruses.
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Subtipo H5N1 del Virus de la Influenza A/inmunología , Subtipo H5N2 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Aviar/prevención & control , Genética Inversa , Animales , Pollos , Cloaca/virología , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H5N2 del Virus de la Influenza A/genética , Subtipo H9N2 del Virus de la Influenza A/genética , Subtipo H9N2 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/genética , Gripe Aviar/virología , Orofaringe/virología , Reacción en Cadena en Tiempo Real de la Polimerasa , Resultado del Tratamiento , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/genética , Vacunas de Productos Inactivados/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Vacunas Sintéticas/inmunología , Esparcimiento de VirusRESUMEN
We report evidence for a narrow structure, X(5568), in the decay sequence X(5568)âB_{s}^{0}π^{±}, B_{s}^{0}âJ/ψÏ, J/ψâµ^{+}µ^{-}, ÏâK^{+}K^{-}. This is evidence for the first instance of a hadronic state with valence quarks of four different flavors. The mass and natural width of this state are measured to be m=5567.8±2.9(stat)_{-1.9}^{+0.9}(syst) MeV/c^{2} and Γ=21.9±6.4(stat)_{-2.5}^{+5.0}(syst) MeV/c^{2}. If the decay is X(5568)âB_{s}^{*}π^{±}âB_{s}^{0}γπ^{±} with an unseen γ, m(X(5568)) will be shifted up by m(B_{s}^{*})-m(B_{s}^{0})â¼49 MeV/c^{2}. This measurement is based on 10.4 fb^{-1} of pp[over ¯] collision data at sqrt[s]=1.96 TeV collected by the D0 experiment at the Fermilab Tevatron collider.
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We report evidence for the simultaneous production of J/ψ and Ï mesons in 8.1 fb^{-1} of data collected at sqrt[s]=1.96 TeV by the D0 experiment at the Fermilab pp[over ¯] Tevatron Collider. Events with these characteristics are expected to be produced predominantly by gluon-gluon interactions. In this analysis, we extract the effective cross section characterizing the initial parton spatial distribution, σ_{eff}=2.2±0.7(stat)±0.9(syst) mb.
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The PCR amplified HA1 fragment of H5N1 (H5HA1) avian influenza virus (AIV) hemagglutinin gene was cloned into pET28a (+) expression vector and expressed in Rosetta Blue (DE3) pLysS cells. The recombinant H5HA1 (rH5HA1) protein purified by passive gel elution after SDS-PAGE of the inclusion bodies reacted specifically with H5N1 serum in Western blot analysis. A subtype specific indirect enzyme linked immunosorbent assay (iELISA) using the rH5HA1 protein as the coating antigen was developed for detecting antibodies to H5 subtype of AIV. The assay had 89.04% sensitivity and 95.95% specificity when compared with haemagglutination inhibition test. The Kappa value of 0.842 indicated a perfect agreement between the tests. The iELISA developed can be used for serosurveillance of avian influenza in chickens.
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Ensayo de Inmunoadsorción Enzimática , Escherichia coli/genética , Subtipo H5N1 del Virus de la Influenza A/genética , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/aislamiento & purificación , Proteínas Virales/biosíntesis , Proteínas Virales/aislamiento & purificación , Western Blotting , Electroforesis en Gel de Poliacrilamida , Escherichia coli/inmunología , Pruebas de Inhibición de Hemaglutinación , Subtipo H5N1 del Virus de la Influenza A/inmunología , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Proteínas Virales/genética , Proteínas Virales/inmunologíaRESUMEN
BACKGROUND: To test the hypothesis that the retraction of anterior teeth has no effect on the dimensions of pharyngeal airway and to evaluate the retraction of anterior teeth on each parameter of pharyngeal airway. METHODS: Twenty-two adult patients of Class I bimaxillary protrusion requiring first premolar extractions with maximum anchorage requirements were selected. The pharyngeal airway and dentofacial parameters of the patients were compared using pre- and post-treatment lateral cephalograms with the help of Student's paired t-test (P < 0.05). The relationship between airway size and dentofacial parameters was also evaluated using Pearson correlation coefficient. RESULTS: The upper and lower lips were retracted by 2.25 and 5.4 mm after retraction of the incisors. The tips of upper and lower incisors were retracted by 7.75 and 7.15 mm, respectively. There was a statistically significant decrease in SPP-SPPW (P < 0.05), U-MPW (P < 0.001), TB-TPPW (P < 0.001), and change in HRGN (P < 0.01). A significant correlation was observed between the amount of retraction of lower incisor and decrease in the pharyngeal airway posterior to soft palate (r = 0.102), tongue (r = 0.322), and change in HRGN (r = 0.265). CONCLUSIONS: The size of the pharyngeal (velopharyngeal and glossopharyngeal) airway reduced and hyoid bone position changed after retraction of the incisors in extraction space in bimaxillary protrusive adult patients.
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BACKGROUND: The efficacy and safety of nab-paclitaxel versus dacarbazine in patients with metastatic melanoma was evaluated in a phase III randomized, controlled trial. PATIENTS AND METHODS: Chemotherapy-naïve patients with stage IV melanoma received nab-paclitaxel 150 mg/m(2) on days 1, 8, and 15 every 4 weeks or dacarbazine 1000 mg/m(2) every 3 weeks. The primary end point was progression-free survival (PFS) by independent radiologic review; the secondary end point was overall survival (OS). RESULTS: A total of 529 patients were randomized to nab-paclitaxel (n = 264) or dacarbazine (n = 265). Baseline characteristics were well balanced. The majority of patients were men (66%), had an Eastern Cooperative Oncology Group status of 0 (71%), and had M1c stage disease (65%). The median PFS (primary end point) was 4.8 months with nab-paclitaxel and 2.5 months with dacarbazine [hazard ratio (HR), 0.792; 95.1% confidence interval (CI) 0.631-0.992; P = 0.044]. The median OS was 12.6 months with nab-paclitaxel and 10.5 months with dacarbazine (HR, 0.897; 95.1% CI 0.738-1.089; P = 0.271). Independently assessed overall response rate was 15% versus 11% (P = 0.239), and disease control rate (DCR) was 39% versus 27% (P = 0.004) for nab-paclitaxel versus dacarbazine, respectively. The most common grade ≥3 treatment-related adverse events were neuropathy (nab-paclitaxel, 25% versus dacarbazine, 0%; P < 0.001), and neutropenia (nab-paclitaxel, 20% versus dacarbazine, 10%; P = 0.004). There was no correlation between secreted protein acidic and rich in cysteine (SPARC) status and PFS in either treatment arm. CONCLUSIONS: nab-Paclitaxel significantly improved PFS and DCR compared with dacarbazine, with a manageable safety profile.
Asunto(s)
Albúminas/uso terapéutico , Dacarbazina/uso terapéutico , Melanoma/diagnóstico , Melanoma/tratamiento farmacológico , Paclitaxel/uso terapéutico , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Alquilantes/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
We present a study of the inclusive production of the X(4140) state with the decay to the J/ψÏ final state in hadronic collisions. Based on 10.4 fb^{-1} of pp[over ¯] collision data collected by the D0 experiment at the Fermilab Tevatron collider, we report the first evidence for the prompt production of an X(4140) state and find the fraction of X(4140) events originating from b hadrons to be f_{b}=0.39±0.07(stat)±0.10(syst). The ratio of the nonprompt X(4140) production rate to the B_{s}^{0} yield in the same channel is R=0.19±0.05(stat)±0.07(syst). The values of the mass M=4152.5±1.7(stat)_{-5.4}^{+6.2}(syst) MeV and width Γ=16.3±5.6(stat)±11.4(syst) MeV are consistent with previous measurements.
RESUMEN
We present a measurement of the forward-backward asymmetry in the production of B(±) mesons, A(FB)(B(±)), using B(±)âJ/ψK(±) decays in 10.4 fb(-1) of ppÌ collisions at sqrt[s]=1.96 TeV collected by the D0 experiment during Run II of the Tevatron collider. A nonzero asymmetry would indicate a preference for a particular flavor, i.e., b quark or Ìb antiquark, to be produced in the direction of the proton beam. We extract A(FB)(B(±)) from a maximum likelihood fit to the difference between the numbers of forward- and backward-produced B(±) mesons. We measure an asymmetry consistent with zero: A(FB)(B(±))=[-0.24±0.41 (stat)±0.19 (syst)]%.
RESUMEN
We present an updated measurement of the B(s)(0) lifetime using the semileptonic decays B(s)(0)âD(s)(-)µ(+)νX, with D(s)(-)âÏπ(-) and ÏâK(+)K(-) (and the charge conjugate process). This measurement uses the full Tevatron Run II sample of proton-antiproton collisions at â[s]=1.96 TeV, comprising an integrated luminosity of 10.4 fb(-1). We find a flavor-specific lifetime τ(fs)(B(s)(0))=1.479±0.010(stat)±0.021(syst) ps. This technique is also used to determine the B(0) lifetime using the analogous B(0)âD(-)µ(+)νX decay with D(-)âÏπ(-) and ÏâK(+)K(-), yielding τ(B(0))=1.534±0.019(stat)±0.021(syst) ps. Both measurements are consistent with the current world averages, and the B(s)(0) lifetime measurement is one of the most precise to date. Taking advantage of the cancellation of systematic uncertainties, we determine the lifetime ratio τ(fs)(B(s)(0))/τ(B(0))=0.964±0.013(stat)±0.007(syst).