OBJECTIVES To report on a 10 year follow up of patients with idiopathic Parkinson’s disease, particularly with respect to mortality and the effect of early treatment with bromocriptine. METHODS The ...patients are from the 149 new patients recruited for a double blind, randomised study of low dose levodopa-carbidopa versus low dose bromocriptine. Patients were examined neurologically at least yearly. Neuropsychological examinations were performed at 0, 3, 5, and 10 years. Mortality and cause of death in these patients were compared with the Australian population using standardised mortality ratios (SMRs). Mortality and disease progression were compared by sex and treatment group. Predictors of death within 10 years, nursing home admission, and progression in Columbia score of ⩾20 points were examined by logistic regression analysis. RESULTS Thirteen patients were excluded as having atypical Parkinsonism and six were lost to follow up. All available patients have been followed up for 10 years. Fifty patients (38%) were dead by 10 years and 63 by the last follow up. The SMR was 1.58 for all patients (p<0.001). There was no significant difference in SMRs between the sexes. The mean duration of disease until death was 9.1 years. Parkinson’s disease was thought to have contributed substantially to the death of 30 patients. The most common cause of death was pneumonia. Women progressed at a similar rate to men until 8 years, when the severity of their disease as measured by Hoehn and Yahr stage became greater (p<0.05). Older age of onset correlated with increased risk of death but the SMR was increased even in those aged <70 years (SMR 1.80, p=0.03). Early use of bromocriptine did not reduce mortality or slow progression of disease. One quarter of all patients had been admitted to nursing homes by 10 years. Only four patients were still employed. CONCLUSIONS Mortality in Parkinson’s disease remains increased despite low dose levodopa-carbidopa therapy and no additional benefit was gained from early use of bromocriptine. Duration of disease was similar to that in the era before levodopa.
The influence of partitioning temperature on microstructural evolution during quenching and partitioning was investigated in a 0.38C1.54Mn1.48Si wt.% steel using Mössbauer spectroscopy and ...transmission electron microscopy. η-carbide formation occurs in the martensite during the quenching, holding, and partitioning steps. More effective carbon partitioning from martensite to austenite was observed at 450 than 400°C, resulting in lower martensite carbon contents, less carbide formation, and greater retained austenite amounts for short partitioning times. Conversely, greater austenite decomposition occurs at 450°C for longer partitioning times. Cementite forms during austenite decomposition and in the martensite for longer partitioning times at 450°C.
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Objective
To evaluate whether a particular group of women with intrahepatic cholestasis of pregnancy (ICP), based on their presenting characteristics, would benefit from treatment with ...ursodeoxycholic acid (UDCA).
Design
Secondary analysis of the PITCHES trial (ISRCTN91918806).
Setting
United Kingdom.
Population or Sample
527 women with ICP.
Methods
Subgroup analyses were performed to determine whether baseline bile acid concentrations or baseline itch scores moderated a woman’s response to treatment with UDCA.
Main outcome measures
Bile acid concentration and itch score.
Results
In women with baseline bile acid concentrations less than 40 μmol/l, treatment with UDCA resulted in increased post‐randomisation bile acid concentrations (geometric mean ratio 1.19, 95% CI 1.00–1.41, P = 0.048). A test of interaction showed no significance (P = 0.647). A small, clinically insignificant difference was seen in itch response in women with a high baseline itch score (–6.0 mm, 95% CI −11.80 to −0.21, P = 0.042), with a test of interaction not showing significance (P = 0.640). Further subgroup analyses showed no significance. Across all women there was a weak relationship between bile acid concentrations and itch severity.
Conclusions
There was no subgroup of women with ICP in whom a beneficial effect of treatment with UDCA on bile acid concentration or itch score could be identified. This confirms that its routine use in women with this condition for improvement of bile acid concentration or itch score should be reconsidered.
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PITCHES: No group of women with ICP has been found in whom UDCA reduces bile acid concentrations or pruritus.
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PITCHES: No group of women with ICP has been found in whom UDCA reduces bile acid concentrations or pruritus.
Background: Global environmental change is exacerbating human vulnerability to adverse atmospheric conditions including air pollution, aeroallergens such as pollen, and extreme weather events. Public ...information and advisories are a central component of responses to mitigate the human impacts of environmental hazards. Digital technologies are emerging as a means of providing personalised, timely and accessible warnings. Method: We describe AirRater, an integrated online platform that combines symptom surveillance, environmental monitoring, and notifications of changing environmental conditions via a free smartphone app. It was developed and launched in Tasmania, Australia (population 510 000), with the aim of reducing health impacts and improving quality of life in people with conditions such as asthma and allergic rhinitis. We present environmental data, user uptake and results from three online evaluation surveys conducted during the first 22 months of operation, from October 2015 through August 2017. Results: There were 3,443 downloads of the app from all regions of Tasmania. Of the 1,959 individuals who registered, 79% reported having either asthma or allergic rhinitis. Downloads increased during adverse environmental conditions and following publicity. Symptom reports per active user were highest during spring (72%), lowest in autumn (37%) and spiked during periods of reduced air quality. In response to online surveys, most users reported that the app was useful and had improved their understanding of how environmental conditions affect their health, and in some cases had prompted action such as the timely use of medication. Conclusion: Active engagement and consistent positive feedback from users demonstrates the potential for considerable individual, clinical and wider public health benefits from integrated and personalised monitoring systems such as AirRater. The perceived health benefits require objective verification, and such systems need to address several challenges in providing timely, reliable and valid environmental data.
Cancer-testis genes mapping to the X chromosome have common expression patterns and show similar responses to modulators of epigenetic mechanisms. We asked whether cancer-testis gene expression ...occurred coordinately, and whether it correlated with variables of disease and clinical outcome of non-small cell lung cancer (NSCLC).
Tumors from 523 NSCLC patients undergoing surgery were evaluated for the expression of nine cancer-testis genes (NY-ESO-1, LAGE-1, MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, CT7/MAGE-C1, SSX2, and SSX4) by semiquantitative PCR. Clinical data available for 447 patients were used to correlate cancer-testis expression to variables of disease and clinical outcome.
At least one cancer-testis gene was expressed by 90% of squamous carcinoma, 62% of bronchioloalveolar cancer, and 67% of adenocarcinoma samples. Statistically significant coexpression was observed for 34 of the 36 possible cancer-testis combinations. Cancer-testis gene expression, either cumulatively or individually, showed significant associations with male sex, smoking history, advanced tumor, nodal and pathologic stages, pleural invasion, and the absence of ground glass opacity. Cox regression analysis revealed the expression of NY-ESO-1 and MAGE-A3 as markers of poor prognosis, independent of confounding variables for adenocarcinoma of the lung.
Cancer-testis genes are coordinately expressed in NSCLC, and their expression is associated with advanced disease and poor outcome.
This study evaluated the effect of 4 criteria for determining the end-point of milking on milk yield, milk composition, completeness of milking-out, teat skin condition, somatic cell count (SCC), and ...the incidence of clinical mastitis (CM) in pasture-based dairy cows milked over 35 wk. The objective was to reduce milking duration without affecting milk production, SCC, or CM. Milking end-point treatments were as follows: cluster removed at a milk flow rate of 0.2 kg/min (ACR200); cluster removed at a milk flow rate of 0.4 kg/min (ACR400); cluster removed at a milk flow rate of 0.2 kg/min or at a maximum cluster attachment time from d 5 of lactation (MaxTEarly); and cluster removed at a milk flow rate of 0.2 kg/min until an average of 63±21 d in milk, then cluster removed at a milk flow rate of 0.2 kg/min or a maximum cluster attachment time (MaxTPeak). Maximum cluster attachment times were set at 7.5min and 5.4min for morning and afternoon milkings, respectively. Cows (approximately 94/treatment) were assigned to treatment at calving and milked twice daily at intervals of 9 and 15h. Milking duration was shorter for ACR400, MaxTEarly, and MaxTPeak compared with ACR200. During wk 1 to 15, milk, protein, and lactose yields were less for MaxTEarly than for ACR400 and MaxTPeak, but not different from ACR200. During wk 16 to 35 and over the entire experiment, total milk, fat, protein, and lactose yields did not differ among treatments. Teat condition did not differ among the 4 treatments. Postmilking strip yield in wk 12 was greatest for MaxTEarly and least for ACR200; at wk 27, however, treatment had no effect on the completeness of milking-out. No differences were observed in either teat condition or the proportion of cows with at least 1 case of CM during the 35 wk. Somatic cell count was low across all treatments, but highest for ACR400. Increasing the automatic cluster remover threshold setting from 0.2 to 0.4 kg/min decreased milking duration without affecting milk production, CM, or teat condition. Combining a cluster removal milk flow threshold setting with a maximum cluster attachment time, when applied from either early lactation or from peak lactation, reduced milking duration without affecting milk production, CM, or SCC. Both strategies have potential to improve milking efficiency in dairy herds in which premilking preparation is minimal.
Perspectives on Quenching and Tempering 4340 Steel Clarke, A. J.; Klemm-Toole, J.; Clarke, K. D. ...
Metallurgical and materials transactions. A, Physical metallurgy and materials science,
10/2020, Letnik:
51, Številka:
10
Journal Article
Perspectives on Quenching and Tempering 4340 Steel Clarke, A. J.; Klemm-Toole, J.; Clarke, K. D. ...
Metallurgical and materials transactions. A, Physical metallurgy and materials science,
10/2020, Letnik:
51, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Steels are ubiquitous due to their affordability and the landscape of useful properties that can be generated for engineering applications. But to further expand the performance envelope, one must be ...able to understand and control microstructure development by alloying and processing. Here we use multiscale, advanced characterization to better understand the structural and chemical evolution of AISI 4340 steel after quenching and tempering (Q&T), including the role of quench rate and short-time, isothermal tempering below 573 K (300 °C), with an emphasis on carbide formation. We compare the microstructure and/or property changes produced by conventional tempering to those produced by higher temperature, short-time “rapid” tempering. We underscore that no single characterization technique can fully capture the subtle microstructure changes like carbon redistribution, transition carbide and/or cementite formation, and retained austenite decomposition that occur during Q&T. Only the use of multiple techniques begins to unravel these complexities. After controlled fast or slow quenching,
η
transition carbides clearly exist in the microstructure, likely associated with autotempering of this high martensite start temperature (
M
s
) steel. Isothermal tempering below 598 K (325 °C) results in the relief of carbon supersaturation in the martensite, primarily by the formation of
η
transition carbides that exhibit a range of carbon levels, seemingly without substitutional element partitioning between the carbide and matrix phases. Hägg transition carbide is present between 300 °C and 325 °C. After conventional tempering at or above 598 K (325 °C) for 2 h, cementite is predominant, but small amounts of cementite are also present in other conditions, even after quenching. Previous work has indicated that silicon (Si) and substitutional elements partition between the cementite, which initially forms under paraequilibrium conditions, and the matrix. Phosphorous (P) may also be preferentially located at cementite/matrix interfaces after high temperature tempering. Slower quench rates result in greater amounts of retained austenite compared to those after fast quenching, which we attribute to increased austenite stability resulting from “autopartitioning”. Rapid, high temperature tempering is also found to diminish tempered martensite embrittlement (TME) believed to be associated with the extent of austenite decomposition, resulting in mechanical properties not attainable by conventional tempering, which may have important implications with respect to industrial heat treatment processes like induction tempering. Controlling the amount and stability of retained austenite is not only relevant to the properties of Q&T steels, but also next-generation advanced high strength steels (AHSS) with austenite/martensite mixtures.
Intrahepatic cholestasis of pregnancy (ICP) is the commonest gestational liver disease. The risk of adverse fetal outcome has been associated with the severity of maternal hypercholanemia after ...diagnosis.
To investigate whether there is a relationship between the severity and timing of onset of hypercholanemia and the risk of meconium-stained amniotic fluid (MSAF) and adverse neonatal events.
The study included 382 pregnancies complicated by ICP managed at a referral hospital in Buenos Aires (Argentina) between June 2009 and December 2013. The patients were classified into three groups according to the severity of hypercholanemia at diagnosis; mild (10-19.9 μmol/L), moderate (20-39.9 μmol/L) and severe (≥40 μmol/L). Their clinical characteristics and pregnancy outcomes were investigated in a prospective observational study.
Higher risk of MSAF was observed when ICP appeared early in gestation or when hypercholanemia was more severe. Taking both parameters into account an MSAF risk factor (MRF) was defined. Based on a model of positive/negative predictive values, a cut-off point of MRF = 3 was selected, which prioritized sensitivity versus specificity. In ICP patients with MRF>3, the probability of MSAF was enhanced 4-fold. An increase in the frequency of MSAF was also associated with higher serum levels at diagnosis of alanine transaminase, alkaline phosphatase and direct bilirubin.
The risk of MSAF is associated not only with the magnitude of hypercholanemia at diagnosis but also with the early gestational onset of raised maternal serum bile acids.
The Juno Microwave Radiometer (MWR) is a six-frequency scientific instrument designed and built to investigate the deep atmosphere of Jupiter. It is one of a suite of instruments on NASA’s New ...Frontiers Mission Juno launched to Jupiter on August 5, 2011. The focus of this paper is the description of the scientific objectives of the MWR investigation along with the experimental design, observational approach, and calibration that will achieve these objectives, based on the Juno mission plan up to Jupiter orbit insertion on July 4, 2016. With frequencies distributed approximately by octave from 600 MHz to 22 GHz, the MWR will sample the atmospheric thermal radiation from depths extending from the ammonia cloud region at around 1 bar to pressure levels as deep as 1000 bars. The primary scientific objectives of the MWR investigation are to determine the presently unknown dynamical properties of Jupiter’s subcloud atmosphere and to determine the global abundance of oxygen and nitrogen, present in the atmosphere as water and ammonia deep below their respective cloud decks. The MWR experiment is designed to measure both the thermal radiation from Jupiter and its emission-angle dependence at each frequency relative to the atmospheric local normal with high accuracy. The antennas at the four highest frequencies (21.9, 10.0, 5.2, and 2.6 GHz) have ∼12° beamwidths and will achieve a spatial resolution approaching 600 km near perijove. The antennas at the lowest frequencies (0.6 and 1.25 GHz) are constrained by physical size limitations and have 20° beamwidths, enabling a spatial resolution of as high as 1000 km to be obtained. The MWR will obtain Jupiter’s brightness temperature and its emission-angle dependence at each point along the subspacecraft track, over angles up to 60° from the normal over most latitudes, during at least six perijove passes after orbit insertion. The emission-angle dependence will be obtained for all frequencies to an accuracy of better than one part in
10
3
, sufficient to detect small variations in atmospheric temperature and absorber concentration profiles that distinguish dynamical and compositional properties of the deep Jovian atmosphere.
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