The dispersion-brightness relation for fast radio bursts from a wide-field survey.

Despite considerable efforts over the past decade, only 34 fast radio bursts-intense bursts of radio emission from beyond our Galaxy-have been reported1,2. Attempts to understand the population as a whole have been hindered by the highly heterogeneous nature of the searches, which have been conducted with telescopes of different sensitivities, at a range of radio frequencies, and in environments corrupted by different levels of radio-frequency interference from human activity. Searches have been further complicated by uncertain burst positions and brightnesses-a consequence of the transient nature of the sources and the poor angular resolution of the detecting instruments. The discovery of repeating bursts from one source3, and its subsequent localization4 to a dwarf galaxy at a distance of 3.7 billion light years, confirmed that the population of fast radio bursts is located at cosmological distances. However, the nature of the emission remains elusive. Here we report a well controlled, wide-field radio survey for these bursts. We found 20, none of which repeated during follow-up observations between 185-1,097 hours after the initial detections. The sample includes both the nearest and the most energetic bursts detected so far. The survey demonstrates that there is a relationship between burst dispersion and brightness and that the high-fluence bursts are the nearby analogues of the more distant events found in higher-sensitivity, narrower-field surveys5.

Aspectos clínicos e histológicos da demodicose canina localizada e generalizada / Clinical and histological aspects of localized and generalized canine demodicosis

Demodicose é uma afecção cutânea causada pelo ácaro Demodex sp. diagnosticada com frequência na rotina clínica veterinária. Objetivou-se descrever as manifestações clínicas e histológicas de cães com demodicose nas formas localizada e generalizada, relacionando a quantidade de ácaros e os achados microscópicos ao quadro clínico. Foram estudados 46 cães, sendo 28 com demodicose generalizada e 18 com a forma localizada da doença, dos quais todos possuíam raspados de pele positivo. Destes caninos foram anotados dados de lesões macroscópicas em ficha dermatológica e coletaram-se amostras de pele para estudo microscópico. A análise histológica foi realizada por três avaliadores e os dados registrados sem comunicação entre os mesmos, sendo considerado o resultado que mais ocorreu. Alopecia, descamação, eritema e crostas foram lesões clínicas comuns às duas formas de apresentação da doença que mais ocorreram. Inflamação histológica dermal grave ocorreu especialmente nos cães com doença localizada e generalizada que possuíam piodermite concomitante e ácaros Demodex sp. foram visualizados com intensidade entre moderada e acentuada na maioria dos cães com ambas as formas da enfermidade. Perifoliculite foi a alteração folicular microscópica mais evidenciada nos caninos deste estudo, seguida por foliculite mural e furunculose que tiveram maior ocorrência relativa nos cães com demodicose localizada. De acordo com os resultados obtidos verificou-se que a gravidade das lesões histológicas não corresponde necessariamente à forma de apresentação clínica da enfermidade, além disso, a quantidade de ácaros não demonstrou ser indicativa de lesões clínicas localizadas ou generalizadas, bem como não é possível diferenciar a doença clínica através do exame histopatológico.(AU)

Demodicosis is a skin condition caused by Demodex mite, frequently diagnosed in clinical routine. The purpose of this study was to compare the clinical and histological manifestations of localized and generalized demodicosis in dogs, relating the amount of mites and microscopic lesions. The study group was formed by 46 dogs, 28 with generalized demodicosis, and 18 with the localized form of the disease, all of them with positive skin scrapings. Macroscopic lesions data in dermatological form were noted, and skin samples were collected for microscopic study. The histopathological analysis was individually performed by three reviewers without intercommunication, being considered the result that more occurred. Alopecia, scaling, erythema, and crusting were the most common clinical lesions in both forms of the disease. Histological severe dermatitis occurred especially in dogs with localized and generalized disease that had concomitant pyoderma and Demodex sp. mites were visualized with intensity moderate and severe in the most dogs with both forms of the diseases. Perifolliculitis was the most evident microscopic follicular change in this study, followed by folliculitis and furunculosis wall, which had higher relative occurrence in dogs with localized demodicosis. According to the results obtained, the severity of histologic lesions does not necessarily correspond to the clinical presentation of the disease, in addition to the amount of mites that apparently is not indicative of localized or generalized clinical lesions, and cannot differentiate clinical disease by histopathology.(AU)

Encapsulation of nor-ß-lapachone into poly(d,l)-lactide-co-glycolide (PLGA) microcapsules: full characterization, computational details and cytotoxic activity against human cancer cell lines.

In this work, we characterize nor-ß-lapachone-loaded (NßL-loaded) microcapsules prepared using an emulsification/solvent extraction technique. Features such as surface morphology, particle size distribution, zeta potential, optical absorption, Raman and Fourier transform infrared spectra, thermal analysis data, drug encapsulation efficiency, drug release kinetics and in vitro cytotoxicity were studied. Spherical microcapsules with a size of 1.03 ± 0.46 µm were produced with an encapsulation efficiency of approximately 19%. Quantum DFT calculations were also performed to estimate typical interaction energies between a single nor-ß-lapachone molecule and the surface of the microparticles. The NßL-loaded PLGA microcapsules exhibited a pronounced initial burst release. After the in vitro treatment with NßL-loaded microcapsules, a clear phagocytosis of the spheres was observed in a few minutes. The cytotoxic activity against a set of cancer cell lines was investigated.

Controlled Release of Nor-ß-lapachone by PLGA Microparticles: A Strategy for Improving Cytotoxicity against Prostate Cancer Cells.

Prostate cancer is one of the most common malignant tumors in males and it has become a major worldwide public health problem. This study characterizes the encapsulation of Nor-ß-lapachone (NßL) in poly(d,l-lactide-co-glycolide) (PLGA) microcapsules and evaluates the cytotoxicity of the resulting drug-loaded system against metastatic prostate cancer cells. The microcapsules presented appropriate morphological features and the presence of drug molecules in the microcapsules was confirmed by different methods. Spherical microcapsules with a size range of 1.03 ± 0.46 µm were produced with an encapsulation efficiency of approximately 19%. Classical molecular dynamics calculations provided an estimate of the typical adsorption energies of NßL on PLGA. Finally, the cytotoxic activity of NßL against PC3M human prostate cancer cells was demonstrated to be significantly enhanced when delivered by PLGA microcapsules in comparison with the free drug.

Carotid endarterectomy for symptomatic, but "haemodynamically insignificant" carotid stenosis.

OBJECTIVE: Carotid endarterectomy (CEA) guidelines in symptomatic carotid stenosis are based on NASCET and ECST criteria with 70% or greater carotid stenosis as estimated from a catheter angiogram the major indication. This has several problems: (1) lack of reliable correlation between non-invasive imaging and catheter angiography, which has been largely superseded by non-invasive imaging in investigating carotid stenosis; (2) errors inherent in estimating the degree of stenosis from catheter angiography; (3) disregard for the fact that stroke risk also depends on plaque stability, and number of ischaemic events. METHODS: A retrospective review of ischaemic events, imaging results, operative findings, surgical complications and stroke-free follow-up in 31 patients presenting over a 23 year period with TIA/stroke (symptoms lasting > 24 h and/or imaging evidence of infarction) who had 70% or less carotid stenosis (on non-invasive imaging), but nonetheless underwent CEA. RESULTS: Nineteen patients had small strokes, 7 had TIAs and 5 had ocular events; 28 patients had features of unstable plaque on imaging; 19 patients experienced multiple events before CEA. All had haemorrhagic, ruptured plaque at CEA. One patient suffered an intra-operative stroke, only 1 patient suffered a further stroke/TIA (mean follow-up 4.2 years). CONCLUSION: To predict the likelihood of major stroke in symptomatic carotid stenosis and the benefit of CEA, plaque stability and the number of ischaemic events might be as important as an estimate of the degree of stenosis.

Psychosocial impact of screening for intracranial aneurysms in relatives with familial subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: In families with > or =2 relatives with intracranial aneurysms (IAs), screening for IAs in asymptomatic first-degree relatives is often recommended. We assessed the long-term psychosocial impact of such screening. METHODS: We identified all persons with IA (screen-positives) and matched them for age and sex with 2 controls without IA (screen-negatives) from hospital-based registers of familial IA. Persons underwent telephone interviews using questionnaires that covered the areas of psychosocial impact of screening, health-related quality of life (HRQoL), and mood. Data were compared between screen-positives and screen-negatives, and with reference populations. RESULTS: Overall, 105 persons from 33 families with IA were included, of whom 35 were screen-positive and 70 were screen-negative. Of the screen-positives, 12 (44%) had reduced their work and 23 (66%) had experienced changes in > or =1 area of independence, self-esteem, future outlook, or personal relationships. In contrast, only 1 (2%) screen-negative person had stopped working and 12 (17%) others had experienced changes in their self-esteem, future outlook, or relationships. Screen-positives had lower HRQoL compared with screen-negatives and the reference population, whereas both screen groups had higher mean depression scores than the reference population. Despite these effects, only 3 persons regretted participating in screening. CONCLUSIONS: Although screening for IA is an important preventative strategy in high-risk individuals, it is associated with considerable psychosocial effects, both positive and negative. Greater awareness of such outcomes, and appropriate intervention where necessary, would appear to be a necessary component of IA screening programs.

Is there a temporal pattern in the occurrence of subarachnoid hemorrhage in the southern hemisphere? Pooled data from 3 large, population-based incidence studies in Australasia, 1981 to 1997.

BACKGROUND AND PURPOSE: Publications on the temporal pattern of the occurrence of subarachnoid hemorrhage (SAH) have produced conflicting results. Variations between studies may relate to the relatively small numbers of SAH cases analyzed, including those in meta-analyses. METHODS: We identified all cases of SAH from 3 well-designed population-based studies in Australia (Adelaide, Hobart, and Perth) and New Zealand (Auckland) during 3 periods between 1981 and 1997. The diagnosis of SAH was confirmed with CT, cerebral angiography, cerebrospinal fluid analysis, or autopsy in all cases. Information on the time of occurrence of each event was obtained. Risk ratios (RRs) and 95% CIs were calculated using Poisson regression, with age, sex, smoking status, and history of hypertension entered in the model as covariates. RESULTS: A total of 783 cases of SAH were registered. Age- and sex-adjusted RRs of SAH occurrence were highest in the period between 6 AM and 12 MIDNIGHT (RR 3.2, 95% CI 2.4-4.3) and in winter and spring (RR 1.3, 95% CI 1.1-1.5; RR 1.3, 95% CI 1.1-1.5; respectively). No particular pattern of SAH occurrence was observed according to the day of the week. Restriction of the analyses to proved aneurysmal SAH did not substantially change the point estimates. CONCLUSIONS: Circadian and circaseptan (weekly) fluctuations of SAH occurrence in the southern hemisphere are similar to those in the northern hemisphere, but the occurrence of SAH in Australasia exhibits clear seasonal (winter and spring) peaks.

Contribution of prevention to vascular cerebral disease management.

BACKGROUND: Epidemiological studies suggest that significant reductions in the incidence of stroke, as with coronary heart disease, can be expected by reducing the prevalence or shifting the distribution of risk factors across the entire population. Thus, identifying risk factors and intervening to control or modify them remains the most important means of further reducing the incidence and case fatality of stroke in developed countries, and controlling the emerging epidemic of cardiovascular disease in developing countries. All people should be encouraged to stop smoking, reduce weight, and increase physical activity and the consumption of fruit and vegetables. METHODS: The high-risk strategy involves the identification and management of people at high risk of developing stroke. Therapies of proven benefit in the prevention of stroke among certain individuals are blood pressure lowering therapy, antiplatelet therapy, anticoagulation therapy and carotid endarterectomy. Evidence is mounting that aggressive treatment of hypercholestrolaemia and hyperglycaemia is also effective in reducing the risk of stroke, but the role of aspirin and carotid endarterectomy in the primary prevention of stroke remains uncertain. This article will review strategies for the prevention of stroke, except blood pressure lowering therapy, which is discussed elsewhere, and address some of the questions about which individuals have the most to gain from various interventions.

Spectrum of primary intracerebral haemorrhage in Perth, Western Australia, 1989-90: incidence and outcome.

In a population based register of stroke (n = 536) compiled in Perth, Western Australia during an 18 month period in 1989-90, 60 cases (11%) of primary intracerebral haemorrhage were identified among 56 persons (52% men). The mean age of these patients was 68 (range 23-93) and 46 (77%) events were first ever strokes. The crude annual incidence was 35 per 100,000, with a peak in the eighth decade, and a male predominance. Deep and lobar haemorrhages each accounted for almost one third of all cases. The clinical presentations included sudden coma (12%), headache (8%), seizures (8%), and pure sensory-motor stroke (3%). Primary intracerebral haemorrhage was the first presentation of leukaemia in two cases (both fatal) and it followed an alcoholic binge in four cases. 55% had a history of hypertension. 16 (27%) patients, half of whom had a history of hypertension, were taking antiplatelet agents, and one patient was taking warfarin. There were only two confirmed cases of amyloid angiopathy. The overall 28 day case fatality was 35%, but this varied from 100% for haemorrhages in the brainstem to 22% for those in the basal ganglionic or thalamic region. Other predictors of early death were intraventricular extension of blood, volume of haematoma, mass effect, and coma and severe paresis at onset. Although based on small numbers, these data confirm the heterogeneous nature of primary intracerebral haemorrhage, but they also suggest a different clinical spectrum of this type of stroke in the community compared with the experience of specialist neurological units.

The role of lifestyle factors in the etiology of stroke. A population-based case-control study in Perth, Western Australia.

BACKGROUND AND PURPOSE: We sought to examine risk factors for all strokes and for ischemic stroke and primary intracerebral hemorrhage separately. METHODS: This was a population-based case-control study. Each case subject meeting World Health Organization criteria for stroke (n = 536) from a population-based register of acute cerebrovascular events compiled in Perth, Western Australia, in 1989 to 1990 was matched for age and sex with up to five control subjects drawn from the same geographical area. Objective confirmation of the type of stroke was available from computed tomography, magnetic resonance imaging, or necropsy for 86% of the case subjects. Data on medical history and lifestyle factors were collected from case and control subjects by interview of the subject or a proxy informant. RESULTS: Current smoking, consumption of meat more than four times weekly, and a history of hypertension or intermittent claudication were each associated with increased risk in multivariate models for all strokes and for all first-ever strokes. Consumption of 1 to 20 g/d alcohol in the preceding week was associated with a significant reduction in the risk of all strokes, all ischemic strokes, and of primary intracerebral hemorrhage, while eating fish more than two times per month appeared to protect against first-ever stroke and against primary intracerebral hemorrhage. Diabetes mellitus was associated with a significantly increased risk of ischemic stroke but a decreased risk of hemorrhagic stroke. CONCLUSIONS: Risk factors for ischemic and hemorrhagic stroke are not exactly the same. Changes in lifestyle relating to tobacco and diet might make important contributions to further reductions in the incidence of stroke.

Hybrid acousto-optic and digital equalization for microwave digital radio channels.

Digital radio transmission systems use complex modulation schemes that require powerful signal-processing techniques to correct channel distortions and to minimize bit error rates. We propose combining the computation power of acousto-optic processing and the accuracy of digital processing to produce a hybrid channel equalizer that exceeds the performance of digital equalization alone. Analysis shows that a hybrid equalizer for 256-level quadrature amplitude modulation (QAM) performs better than a digital equalizer for 64-level QAM.

Treatment of malignancy-associated hypercalcemia with norethisterone: a case report.

Hypercalcemia is a common cause of morbidity in cancer patients. The mechanism of malignancy-associated hypercalcemia includes increased bone resorption and decreased renal calcium clearance which also occur in primary hyperparathyroidism. Norethisterone can inhibit bone resorption and has recently been shown to be effective treatment for mild hyperparathyroidism in post menopausal women. We report the successful use for the first time of norethisterone (5 mg daily) in a case of malignancy-associated hypercalcemia after other standard agents failed.

Hepatic granulomas: a 15-year experience in the Royal Adelaide Hospital.

The clinical and pathological associations of hepatic granulomas in patients who presented to the Royal Adelaide Hospital between January 1, 1968 and February 29, 1984 were reviewed retrospectively. Cases of primary biliary cirrhosis were excluded. Of 59 patients with hepatic granulomas, clear associations with diseases were identified in 42 (71%) patients. These were sarcoidosis (seven cases), chronic liver disease (12 cases), biliary tract disease (three cases), tuberculosis (four cases), Q-fever (three cases), other infections (four cases), drug hypersensitivity (four cases) and neoplasms (five cases). Ten patients had multiple associations and five other patients presented without any clearly defined cause for granulomas. Three of these latter patients presented with an acute febrile illness, showed hepatomegaly and had abnormal results of liver function tests. These cases may represent the entity that is labeled "idiopathic granulomatous hepatitis". Two other patients abused alcohol. Granulomas were categorized morphologically as microgranulomas, macrogranulomas and lipogranulomas according to their size, organization and the presence of fat droplets. Microgranulomas were associated with diseases of short duration and less architectural disturbance of the liver parenchyma. The presence of granulomas did not confer any prognostic implication over and above that of the associated disease.