Background: The purpose of this study was to evaluate the association of circulating tumour cell (CTC) counts, before and after commencing treatment, with overall survival (OS) in patients with ...castration-resistant prostate cancer (CRPC).
Experimental design: A 7.5ml of blood was collected before and after treatment in 119 patients with CRPC. CTCs were enumerated using the CellSearch®System.
Results: Higher CTC counts associated with baseline characteristics portending aggressive disease. Multivariate analyses indicated that a CTC ≥5 was an independent prognostic factor at all time points evaluated. Patients with baseline CTC ≥5 had shorter OS than those with <5 median OS 19.5 versus >30 months, hazard ratio (HR) 3.25, P = 0.012; patients with CTC >50 had a poorer OS than those with CTCs 5–50 (median OS 6.3 versus 21.1 months, HR 4.1, P < 0.001). Patients whose CTC counts reduced from ≥5 at baseline to <5 following treatment had a better OS compared with those who did not. CTC counts showed a similar, but earlier and independent, ability to time to disease progression to predict OS.
Conclusion: CTC counts predict OS and provide independent prognostic information to time to disease progression; CTC dynamics following therapy need to be evaluated as an intermediate end point of outcome in randomised phase III trials.
The neurodegenerative disorder Huntington’s disease (HD) is typically characterized by extensive loss of striatal neurons and the midlife onset of debilitating and progressive chorea, dementia, and ...psychological disturbance. HD is caused by a CAG repeat expansion in the Huntingtin (HTT) gene, translating to an elongated glutamine tract in the huntingtin protein. The pathogenic mechanism resulting in cell dysfunction and death beyond the causative mutation is not well defined. To further delineate the early molecular events in HD, we performed RNA-sequencing (RNA-seq) on striatal tissue from a cohort of 5-y-old OVT73-line sheep expressing a human CAG-expansion HTT cDNA transgene. Our HD OVT73 sheep are a prodromal model and exhibit minimal pathology and no detectable neuronal loss. We identified significantly increased levels of the urea transporter SLC14A1 in the OVT73 striatum, along with other important osmotic regulators. Further investigation revealed elevated levels of the metabolite urea in the OVT73 striatum and cerebellum, consistent with our recently published observation of increased urea in postmortem human brain from HD cases. Extending that finding, we demonstrate that postmortem human brain urea levels are elevated in a larger cohort of HD cases, including those with low-level neuropathology (Vonsattel grade 0/1). This elevation indicates increased protein catabolism, possibly as an alternate energy source given the generalized metabolic defect in HD. Increased urea and ammonia levels due to dysregulation of the urea cycle are known to cause neurologic impairment. Taken together, our findings indicate that aberrant urea metabolism could be the primary biochemical disruption initiating neuropathogenesis in HD.
This study was designed to evaluate the prevalence of Clostridium difficile contamination of retail chicken. Chicken legs, thighs and wings were purchased using a standardized method from retail ...outlets across Ontario, Canada. Selective culture was used for qualitative and quantitative detection of C. difficile. Clostridium difficile was isolated from 26/203 (12·8%) chicken samples; 10/111 (9·0%) thighs, 13/72 (18%) wings and 3/20 (15%) legs (P = 0·19). All isolates were ribotype 078, a strain that has been associated with food animals and potentially community-associated disease in humans. All positive samples were positive only on enrichment culture. Clostridium difficile could be found relatively commonly in retail chicken meat, albeit at low levels. This is the first study to report C. difficile in chicken meat. Contamination of meat with C. difficile strains implicated in human infections raises concerns about food as a source of C. difficile infection. The relevance of food contamination is completely unclear at this point but food should be investigated as a source of infection.
Satellite-derived aerosol optical depth (AOD) observations have been used to estimate particulate matter smaller than 2.5 μm (PM2.5 ). However, such a relationship could be affected by the ...representativeness of satellite-derived AOD to surface aerosol particle mass concentration and satellite AOD data quality. Using purely measurement-based methods, we have explored the impacts of data quality and representativeness on the AOD-inferred PM2.5 / AOD relationship for the contiguous United States (CONUS). This is done through temporally and spatially collocated data sets of PM2.5 and AOD retrievals from Aqua/Terra Moderate Resolution Imaging Spectroradiometer (MODIS), Multi-angle Imaging Spectroradiometer (MISR), and Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP). These analyses show that improving data quality of satellite AOD, such as done with data assimilation-grade retrievals, increases their correlation with PM2.5 . However, overall correlation is relatively low across the CONUS. Also, integrated extinction observed within 500 m above ground level (a.g.l.), as measured by CALIOP, is not well representative of the total column AOD. Surface aerosol in the eastern CONUS is better correlated with total column AOD than in the western CONUS. The best correlation values are found for estimated dry mass CALIOP extinction at 200-300 m a.g.l. and PM2.5 , but additional work is needed to address the ability of using actively sensed AOD as a proxy for PM2.5 concentrations.
The Northern Hemisphere has been warmer since 1980 than at any other time during the last 2000
years. The observed increase in temperature has been generally higher in northern than in southern ...European seas, and higher in enclosed than in open seas. Although European marine ecosystems are influenced by many other factors, such as nutrient enrichment and overfishing, every region has shown at least some changes that were most likely attributable to recent climate change. It is expected that within open systems there will generally be (further) northward movement of species, leading to a switch from polar to more temperate species in the northern seas such as the Arctic, Barents Sea and the Nordic Seas, and subtropical species moving northward to temperate regions such as the Iberian upwelling margin. For seas that are highly influenced by river runoff, such as the Baltic Sea, an increase in freshwater due to enhanced rainfall will lead to a shift from marine to more brackish and even freshwater species. If semi-enclosed systems such as the Mediterranean and the Black Sea lose their endemic species, the associated niches will probably be filled by species originating from adjacent waters and, possibly, with species transported from one region to another via ballast water and the Suez Canal. A better understanding of potential climate change impacts (scenarios) at both regional and local levels, the development of improved methods to quantify the uncertainty of climate change projections, the construction of usable climate change indicators, and an improvement of the interface between science and policy formulation in terms of risk assessment will be essential to formulate and inform better adaptive strategies to address the inevitable consequences of climate change.
► Recent and future impacts of climate change on European marine ecosystems are listed. ► All European seas have shown changes that can be attributed to recent climate change. ► Northern seas are expected to switch from polar to more temperate species. ► Semi-enclosed seas are more vulnerable to loss of endemic species than open seas. ► Adaptive management strategies need usable climate change indicators.
The objective of the study was to determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) contamination of retail meat and to determine the level of contamination. Pork (pork ...chops and ground pork), ground beef and chicken (legs, wings and thighs) were purchased at retail outlets in four Canadian provinces and tested for the presence of methicillin-resistant Staph. aureus using qualitative and quantitative methods. MRSA was isolated from 9·6% of pork, 5·6% of beef and 1·2% of chicken samples (P = 0·0002). Low levels of MRSA were typically present, with 37% below the detection threshold for quantification and <100 CFU g⁻¹ present in most quantifiable samples. All isolates were classified as Canadian epidemic MRSA-2 (CMRSA-2) by pulsed field gel electrophoresis (PFGE), with two different PFGE subtypes, and were spa type 24/t242. MRSA contamination of retail meat is not uncommon. While CMRSA-2, a human epidemic clone, has been found in pigs in Canada, the lack of isolation of livestock-associated ST398 was surprising. The relevance of MRSA contamination of meat is unclear but investigation is required because of the potential for exposure from food handling. Sources of contamination require investigation because these results suggest that human or animal sources could be involved.
Many theories beyond the Standard Model postulate short-range modifications to gravity which produce deviations of Newton's gravitational potential from a strict 1/r dependence. It is common to ...analyze experiments searching for these modifications using a potential of the form V′(r) = − GMm/r 1 + α exp (−r/λ). The best present constraints on α for λ < 100 nm come from neutron scattering and often employ comparisons of different measurements of the coherent neutron scattering amplitudes b. We analyze the internal consistency of existing data from two different types of measurements of low-energy neutron scattering amplitudes: neutron interferometry, which involves squared momentum transfers q2 = 0, and neutron gravity reflectometry, which involves squared momentum transfers q2 = 8m Vopt where m is the neutron mass and V opt is the neutron optical potential of the medium. We show that the fractional difference Δb/|b| averaged over the seven elements where high precision data exist on the same material from both measurement methods is 2.2 ± 1.4 × 10−4. We also show that Δ b | b | for these data is insensitive both to exotic Yukawa interactions and also to the electromagnetic neutron-atom interactions proportional to the neutron-electron scattering length bne and the neutron polarizability scattering amplitude bpol. This result will be useful in any future global analyses of neutron scattering data to determine bne and bound α and λ. We also discuss how various neutron interferometric and scattering techniques with cold and ultracold neutrons can be used to improve the precision of b measurements and make some specific proposals.
As an update to our previous use of the collection 4 Moderate Resolution Imaging Spectroradiometer (MODIS) over-ocean aerosol optical depth (AOD) data, we examined ten years of Terra and eight years ...of Aqua collection 5 data for its potential usage in aerosol assimilation. Uncertainties in the over-ocean MODIS AOD were studied as functions of observing conditions, such as surface characteristics, aerosol optical properties, and cloud artifacts. Empirical corrections and quality assurance procedures were developed and compared to collection 4 data. After applying these procedures, the Root-Mean-Square-Error (RMSE) in the MODIS Terra and Aqua AOD are reduced by 30% and 10-20%, respectively, with respect to AERONET data. Ten years of Terra and eight years of Aqua quality-assured level 3 MODIS over-ocean aerosol products were produced. The newly developed MODIS over-ocean aerosol products will be used in operational aerosol assimilation and aerosol climatology studies, as well as other research based on MODIS products.
Background. Compulsory community service (CS) for health professionals for 12 months was introduced in South Africa (SA) in 1998, starting with medical practitioners. Up to 2014, a total of 17 413 ...newly qualified doctors and ~44 000 health professionals had completed their year of service in public health facilities around the country. While a number of studies have described the experience and effects of CS qualitatively, none has looked at the programme longitudinally. Objectives. To describe the findings and analyse trends from surveys of CS doctors between 2000 and 2014, specifically with regard to their distribution, support, feedback and career plans. Methods. A consecutive cross-sectional descriptive study design was used based on annual national surveys of CS doctors. The study population of between 1 000 and 1 300 each year was surveyed with regard to their origins, allocations, experiences of the year and future career plans. Results. The total study population varied between 1 057 and 1 308 each year, with response rates of 20 - 77%. The average turn-up rate of 89% showed a decreasing tendency, while 77% of respondents were satisfied with the allocation process. Over the 15-year period, the proportion of CS doctors who were black and received a study bursary, and who were allocated to rural areas and district hospitals, increased. The great majority believed that they had made a difference (91%) and developed professionally (81%) over the course of the year, but only about half felt adequately supported clinically and administratively. The attitude towards CS of the majority of respondents shifted significantly from neutral to positive over the course of the 15 years. In terms of future career plans, 50% hoped to specialise, a decreasing minority to go overseas or into private practice, and a constant 15% to work in rural or underserved areas. Conclusions. This study is the first to track the experience of compulsory CS over time in any country in order to describe the trends once it had become institutionalised. The SA experience of CS for doctors over the first 15 years appears to have been a successively positive one, and it has largely met its original objectives of redistribution of health professionals and professional development. Greater attention needs to be given to orientation, management support and clinical supervision, and focusing professional development opportunities on the important minority who are prepared to stay on longer than their obligatory year. CS still needs to be complemented by other interventions to capitalise on its potential.
Electroconvulsive therapy (ECT) is an effective treatment for depression but the extent and persistence of cognitive side-effects remain uncertain. It has been reported that there is little evidence ...that impairments last longer than up to 15 days post-ECT. However, relatively few studies have followed patients for even as long as 1 month post-ECT. Here we report results from a brief cognitive battery given prior to ECT and repeated five times up to 6 months post-ECT.
In a retrospective case-note study of routinely collected clinical data 126 patients treated with ECT completed two neuropsychological tests Cambridge Neuropsychological Test Automated Battery (CANTAB) spatial recognition memory (SRM) and Mini Mental State Examination (MMSE) and two subjective reports of memory function, prior to ECT. Patients were reassessed following ECT and at 1, 3 and 6 months post-ECT although not all patients completed all assessments.
Performance relative to pre-ECT baseline was significantly poorer at each post-ECT assessment up to 3 months post-ECT using the CANTAB SRM, but was improved at 6 months. Conversely, MMSE score showed improvements relative to baseline from 1 month post-ECT. Mood and subjective memory scores improved following ECT and were correlated with one another, but not with either neuropsychological measure.
The CANTAB SRM task revealed reversible cognitive deficiencies relative to a pre-ECT baseline for at least 3 months following ECT, while MMSE score and patients' subjective reports showed only improvement. Visuospatial memory scores eventually exceeded baseline 6 months post-ECT.
PDF
