RESUMEN
Multiple sources must be consulted to determine the most appropriate procedures for the laboratory-based performance evaluation of aqueous oral inhaled products (OIPs) for the primary measures, dose uniformity/delivery, and aerodynamic particle (droplet) size distribution (APSD). These sources have been developed at different times, mainly in Europe and North America, during the past 25 years by diverse organizations, including pharmacopeial chapter/monograph development committees, regulatory agencies, and national and international standards bodies. As a result, there is a lack of consistency across all the recommendations, with the potential to cause confusion to those developing performance test methods. We have reviewed key methodological aspects of source guidance documents identified by a survey of the pertinent literature and evaluated the underlying evidence supporting their recommendations for the evaluation of these performance measures. We have also subsequently developed a consistent series of solutions to guide those faced with the various associated challenges when developing OIP performance testing methods for oral aqueous inhaled products.
Asunto(s)
Agencias Gubernamentales , Aerosoles , Europa (Continente)RESUMEN
Mass and angle distributions for the ^{52}Cr+^{198}Pt and ^{54}Cr+^{196}Pt reactions (both forming ^{250}No) were measured and subtracted, giving new information on fast quasifission mass evolution, and the first direct determination of the dependence of sticking times on angular momentum. TDHF calculations showed good agreement with average experimental values, but experimental mass distributions unexpectedly extended to symmetric splits while the peak yield remained close to the initial masses. This implies a strong role of fluctuations in mass division early in the collision, giving insights into the transition from fast energy dissipative deep-inelastic collisions to quasifission.
RESUMEN
INTRODUCTION: There is limited data on the analytical performance of commercial nucleic acid tests (NATs) for laboratory confirmation of COVID-19 infection. METHODS: Nasopharyngeal, combined nose and throat swabs, nasopharyngeal aspirates and sputum was collected from persons with suspected SARS-CoV-2 infection, serial dilutions of SARS-CoV-2 viral cultures and synthetic positive controls (gBlocks, Integrated DNA Technologies) were tested using i) AusDiagnostics assay (AusDiagnostics Pty Ltd); ii) in-house developed assays targeting the E and RdRp genes; iii) multiplex PCR assay targeting endemic respiratory viruses. Discrepant SARS-CoV-2 results were resolved by testing the N, ORF1b, ORF1ab and M genes. RESULTS: Of 52 clinical samples collected from 50 persons tested, respiratory viruses were detected in 22 samples (42 %), including SARS CoV-2 (nâ¯=â¯5), rhinovirus (nâ¯=â¯7), enterovirus (nâ¯=â¯5), influenza B (nâ¯=â¯4), hMPV (nâ¯=â¯5), influenza A (nâ¯=â¯2), PIV-2 (nâ¯=â¯1), RSV (nâ¯=â¯2), CoV-NL63 (nâ¯=â¯1) and CoV-229E (nâ¯=â¯1). SARS-CoV-2 was detected in four additional samples by the AusDiagnostics assay. Using the in-house assays as the "gold standard", the sensitivity, specificity, positive and negative predictive values of the AusDiagnostics assay was 100 %, 92.16 %, 55.56 % and 100 % respectively. The Ct values of the real-time in-house-developed PCR assay targeting the E gene was significantly lower than the corresponding RdRp gene assay when applied to clinical samples, viral culture and positive controls (mean 21.75 vs 28.1, pâ¯=â¯0.0031). CONCLUSIONS: The AusDiagnostics assay is not specific for the detection SARS-CoV-2. Any positive results should be confirmed using another NAT or sequencing. The case definition used to investigate persons with suspected COVID-19 infection is not specific.
Asunto(s)
Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Nasofaringe/virología , Neumonía Viral/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19 , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Pandemias , SARS-CoV-2 , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Superheavy elements are formed in fusion reactions which are hindered by fast nonequilibrium processes. To quantify these, mass-angle distributions and cross sections have been measured, at beam energies from below-barrier to 25% above, for the reactions of ^{48}Ca, ^{50}Ti, and ^{54}Cr with ^{208}Pb. Moving from ^{48}Ca to ^{54}Cr leads to a drastic fall in the symmetric fission yield, which is reflected in the measured mass-angle distribution by the presence of competing fast nonequilibrium deep inelastic and quasifission processes. These are responsible for reduction of the compound nucleus formation probablity P_{CN} (as measured by the symmetric-peaked fission cross section), by a factor of 2.5 for ^{50}Ti and 15 for ^{54}Cr in comparison to ^{48}Ca. The energy dependence of P_{CN} indicates that cold fusion reactions (involving ^{208}Pb) are not driven by a diffusion process.
RESUMEN
Energy dissipative processes play a key role in how quantum many-body systems dynamically evolve toward equilibrium. In closed quantum systems, such processes are attributed to the transfer of energy from collective motion to single-particle degrees of freedom; however, the quantum many-body dynamics of this evolutionary process is poorly understood. To explore energy dissipative phenomena and equilibration dynamics in one such system, an experimental investigation of deep-inelastic and fusion-fission outcomes in the ^{58}Ni+^{60}Ni reaction has been carried out. Experimental outcomes have been compared to theoretical predictions using time dependent Hartree-Fock and time dependent random phase approximation approaches, which, respectively, incorporate one-body energy dissipation and fluctuations. Excellent quantitative agreement has been found between experiment and calculations, indicating that microscopic models incorporating one-body dissipation and fluctuations provide a potential tool for exploring dissipation in low-energy heavy ion collisions.
RESUMEN
An extended spectroscopic study on the left-through-left circularly polarized reflection spectra of a large number of beetles from the Australasian Scrabaeidae:Cetoniinae of the Lomaptera genus was undertaken. We have obtained a five-category spectral classification. The principal spectral features, which even within the genus range from blue to infrared, are related to structural chirality in the beetle shells. The detailed features of each spectral classification are related to different structural perturbations of the helix, including various pitch values and abrupt twist defects. These spectral characteristics and associated shell structures are confirmed on the basis of simple modelling. An important conclusion from our study is that the simple helical structure resulting in a single symmetric Bragg peak is not the dominant spectral type. Rather the reality is a rich tapestry of spectral types. One intriguing specimen is identified via a scanning electron micrograph to consist of a double interstitial helix leading to a particular double-peak spectrum.
Asunto(s)
Estructuras Animales , Escarabajos , Luz , AnimalesRESUMEN
We present two new modalities for generating chemical maps. Both are mid-IR based and aimed at the biomedical community, but they differ substantially in their technological readiness. The first, so-called "Digistain", is a technologically mature "locked down" way of acquiring diffraction-limited chemical images of human cancer biopsy tissue. Although it is less flexible than conventional methods of acquiring IR images, this is an intentional, and key, design feature. It allows it to be used, on a routine basis, by clinical personnel themselves. It is in the process of a full clinical evaluation and the philosophy behind the approach is discussed. The second modality is a very new, probe-based "s-SNOM", which we are developing in conjunction with a new family of tunable "Quantum Cascade Laser" (QCL) diode lasers. Although in its infancy, this instrument can already deliver ultra-detailed chemical images whose spatial resolutions beat the normal diffraction limit by a factor of â¼1000. This is easily enough to generate chemical maps of the insides of single cells for the first time, and a range of new possible scientific applications are explored.
Asunto(s)
Diagnóstico por Imagen/instrumentación , Diagnóstico por Imagen/métodos , Rayos Infrarrojos , Láseres de Semiconductores , Neoplasias/diagnóstico por imagen , Neoplasias/patología , Análisis de la Célula Individual/instrumentación , Biopsia/métodos , Humanos , Análisis de la Célula Individual/métodosRESUMEN
The effect of rotational disorder on the microwave transmission through thin metallic checkerboard arrays has been experimentally studied. Broad resonant features below the onset of diffraction, attributed to electromagnetic radiation coupling through the structure via the evanescent fields of bound surface waves, are found to be strongly dependent on the electrical connectivity of the surface. By applying rotational disorder to the elements comprising the arrays, with the lattice constant and element size unchanged, the electrical connectivity of the structure can be controlled whilst maintaining periodicity. The results show that rotational disorder can significantly affect transmission only when it changes the structure's connectivity. When the initial structure is just above the connectivity threshold (where the metallic occupancy is 50%), increasing disorder causes the resonant features in transmission to invert as the structure switches from a predominantly connected array to a disconnected array. When approximately half of the connections are broken, the resonant features are suppressed, with scattering loss shown to dramatically increase to as much as 40% of the incident power over a broad frequency range. The result is a thin, highly effective scatterer of microwaves.
RESUMEN
During the early weeks of the 2015 Australian influenza season, influenza B accounted for 67% (821/1,234) of all positive influenza tests in New South Wales. Of 81 successive influenza B viruses characterised, 33 (41%) were from children aged < 16 years; 23/81 (28%) belonged to the B/Victoria lineage. This lineage is not contained in the southern hemisphere's 2015 trivalent influenza vaccine. The significant B/Victoria lineage activity in the southern hemisphere suggests that the quadrivalent vaccine should be considered for the northern hemisphere.
Asunto(s)
Brotes de Enfermedades/prevención & control , Virus de la Influenza B/aislamiento & purificación , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/epidemiología , Vacunación , Australia/epidemiología , Niño , Preescolar , Femenino , Pruebas de Inhibición de Hemaglutinación , Humanos , Lactante , Virus de la Influenza B/inmunología , Gripe Humana/diagnóstico , Gripe Humana/prevención & control , Masculino , Nueva Gales del Sur/epidemiología , Prevalencia , Estaciones del AñoAsunto(s)
Enfermedades de las Aves , Infecciones por Escherichia coli/veterinaria , Falconiformes , Infecciones por Nematodos/veterinaria , Pericardio/patología , Rapaces , Animales , Enfermedades de las Aves/microbiología , Enfermedades de las Aves/parasitología , Conservación de los Recursos Naturales , Infecciones por Escherichia coli/complicaciones , Falconiformes/microbiología , Falconiformes/parasitología , Resultado Fatal , Femenino , Nematodos/clasificación , Infecciones por Nematodos/complicaciones , Rapaces/microbiología , Rapaces/parasitología , Reino UnidoAsunto(s)
Arginina/fisiología , Factor X/fisiología , Mutación , Anciano , Arginina/genética , Factor X/química , Factor X/genética , Humanos , Masculino , Modelos MolecularesRESUMEN
In 1989, the Nature Conservancy Council and the Royal Society for the Protection of Birds commenced reintroduction of the red kite (Milvus milvus) according to International Union for Conservation of Nature criteria. Following 22 years of intensive effort, the red kite reintroduction programme has been a success with an estimated 1000 pairs now breeding in England. Post-release health surveillance is ongoing and has been achieved through radio-tracking, monitoring breeding at nest sites and pathological examinations of any red kites found dead. Tail-mounted radio transmitters were fitted from 1989 with harness-mounted radio transmitters being preferentially used since 2000. Since 2000, 180 individuals have been recovered for postmortem examination. Eighteen of these birds had previously had a harness-mounted radio transmitter fitted and four of these (22 per cent) had moderate to severe lesions associated with the presence of the harness and radio transmitter including chronic necrogranulomatous inflammation, deep muscular exposure and distorted muscular conformation. Failure to breed was also reported in two of these individuals over the preceding year(s), although it is not known whether the presence of the harness contributed to this failure. Duration of deployment may have been a significant factor in the formation of these lesions as those with lesions (n=4) had a statistically significant (P=0.009) longer duration of deployment compared to those without lesions (n=14). No lesions were reported in those red kites fitted with tail-transmitters.
Asunto(s)
Sistemas de Identificación Animal/instrumentación , Bienestar del Animal , Falconiformes/fisiología , Animales , Animales Salvajes , Conservación de los Recursos Naturales , Inglaterra , Falconiformes/lesiones , Vigilancia de la PoblaciónRESUMEN
Since 1989, a red kite Milvus milvus reintroduction programme has been underway in the United Kingdom, with 4-6 week old nestlings brought into captivity and held for 6-8 weeks before reintroduction. As scavengers, red kites may consume unretrieved game, and ingest shot or lead (Pb) fragments in their prey's flesh. We evaluated exposure to Pb in captive and wild red kites by taking blood samples from 125 captive young red kites prior to release, through analysing 264 pellets (regurgitated by wild birds) collected from under a roost site, and analysing Pb concentrations in livers and/or bones of 87 red kites found dead between 1995 and 2003. Lead isotope analyses of livers were also conducted in an effort to identify Pb exposure routes. Forty-six (36.8%) kites sampled prior to release had elevated blood Pb concentrations (201-3340 microg l(-1)). The source of this Pb was probably small fragments of lead ammunition in the carcasses of birds or mammals either fed to the nestlings by their parents or, more likely, subsequently whilst in captivity. Once released, kites were also exposed to lead shot in their food, and a minimum of 1.5-2.3% of regurgitated pellets contained Pb gunshot. Seven of 44 red kites found dead or that were captured sick and died within a few days had elevated (>6 mg kg(-1) dry weight [d.w.]) liver Pb concentrations, and six of these (14%) had concentrations of >15 mg kg(-1) d.w., compatible with fatal Pb poisoning. Post-mortem analyses indicated that two of these birds had died of other causes (poisoning by rodenticide and a banned agricultural pesticide); the remaining four (9%) probably died of Pb poisoning. Bone samples from 86 red kites showed a skewed distribution of Pb concentration, and 18 samples (21%) had Pb concentrations >20 mg kg(-1) d.w., indicating elevated exposure to Pb at some stage in the birds' life. Lead isotopic signatures (Pb (208/206); Pb (206/207)) in liver samples of the majority of kites were compatible with those found in lead shot extracted from regurgitated pellets. Lead isotope ratios found in the livers of kites with very low Pb concentrations were distinct from UK petrol Pb isotopic signatures, indicating that birds were exposed to little residual petrol Pb. We conclude that the primary source of Pb to which red kites are exposed is lead ammunition (shotgun pellets or rifle bullets), or fragments thereof, in their food sources; in some cases exposure appears sufficient to be fatal. We make recommendations to reduce Pb poisoning in both captive and wild red kites and other scavenging species.
Asunto(s)
Contaminantes Ambientales/análisis , Falconiformes/metabolismo , Plomo/análisis , Animales , Huesos/metabolismo , Dieta , Contaminantes Ambientales/metabolismo , Falconiformes/sangre , Armas de Fuego , Plomo/metabolismo , Hígado/metabolismo , ConejosRESUMEN
OBJECTIVES: To describe the prevalence and characteristics of isolates of Neisseria gonorrhoeae grown from urine samples that produced negative results with nucleic acid amplification assays (NAA) targeting the cppB gene. METHODS: An initial cluster of culture positive, but cppB gene based NAA negative, gonococcal infections was recognised. Urine samples and suspensions of gonococci isolated over 9 months in the Northern Territory of Australia were examined using cppB gene based and other non-cppB gene based NAA. The gonococcal isolates were phenotyped by determining the auxotype/serovar (A/S) class and genotyped by pulsed field gel electrophoresis (PFGE). RESULTS: 14 (9.8%) of 143 gonococci isolated were of A/S class Pro(-/)Brpyut, indistinguishable on PFGE and negative in cppB gene based, but not other, NAA. CONCLUSIONS: This cluster represents a temporal and geographic expansion of a gonococcal subtype lacking the cppB gene with consequent loss of sensitivity of NAA dependent on amplification of this target. Gonococci lacking the cppB gene have in the past been more commonly associated with the PAU-/PCU- auxotype, a gonococcal subtype hitherto infrequently encountered in Australia. NAA based on the cppB gene as a target may produce false positive as well as false negative NAA. This suggests that unless there is continuing comparison with culture to show their utility, cppB gene based NAA should be regarded as suboptimal for use either as a diagnostic or supplemental assay for diagnosis of gonorrhoea, and NAA with alternative amplification targets should be substituted.
Asunto(s)
Proteínas de la Membrana Bacteriana Externa/genética , Gonorrea/microbiología , Neisseria gonorrhoeae/aislamiento & purificación , Análisis por Conglomerados , Reacciones Falso Negativas , Gonorrea/genética , Humanos , Neisseria gonorrhoeae/genética , Reacción en Cadena de la Polimerasa/métodosRESUMEN
Allogeneic SCT for myeloma may be curative for young patients, but its role remains controversial because of a reported high TRM in some series. Since 1991, we have performed 25 allografts for myeloma using fully matched sibling donors. Of the 18 evaluable patients, 13 achieved CR at a median time of 2.5 months post-transplant. The five patients who were not in CR when assessed at 3 months received a short course of alpha-interferon and four subsequently achieved CR with this approach at a median of 82 days. One patient who failed to respond to IFN went on to achieve CR after four doses of DLI therapy, thus giving an overall CR rate of 72%. Seven patients have relapsed at a median of 4.7 years post-transplant (range 1.38-7.7 years) including two patients who had received IFN therapy. In five of these cases, relapse has been as a localised area of bone disease or isolated plasmacytoma with no evidence of marrow involvement by trephine biopsy or molecular analysis. All patients with localised relapse were treated with local radiotherapy +/-DLI and four are currently disease free despite two patients having had further treatment for a second localised lesion. Six patients died of TRM (24%) and the OS at 8 years is currently 69% with an EFS of 26%. These results suggest that allogeneic SCT for myeloma can be carried out with an acceptable TRM and a high CR rate. However, late relapses as localised disease may be a frequent finding and may represent foci of myeloma not eradicated by the conditioning. The use of pretransplant MRI scanning and top-up radiotherapy to involved areas may be useful in preventing this type of relapse.
Asunto(s)
Trasplante de Médula Ósea/fisiología , Mieloma Múltiple/terapia , Trasplante de Células Madre , Adulto , Trasplante de Médula Ósea/inmunología , Trasplante de Médula Ósea/mortalidad , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/epidemiología , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Plasmacitoma/terapia , Recurrencia , Estudios Retrospectivos , Trasplante de Células Madre/efectos adversos , Trasplante de Células Madre/mortalidad , Tasa de Supervivencia , Factores de Tiempo , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/inmunología , Trasplante Homólogo/mortalidad , Resultado del TratamientoRESUMEN
We describe a man vaccinated with the 17D204 strain of yellow fever virus, who subsequently died of yellow fever. Sequencing of the NS5-39 untranslated region showed that the virus isolated from the patient was identical to the vaccine strain of the same batch, and different from wild-type virus. Both viruses contained a mutation, although the association of this mutation with virulence is unknown. Severe, rapidly progressive, and ultimately fatal disease can follow use of the 17D204 vaccine strain. There is need for renewed discussion as to the safety of the vaccine and the indications for its use.