Intensity of care in cancer patients in the last year of life: a retrospective data linkage study

Background Delivering high-quality palliative and end-of-life care for cancer patients poses major challenges for health services. We examine the intensity of cancer care in England in the last year of life.Methods We included cancer decedents aged 65+ who died between January 1, 2010 and December 31, 2017. We analysed healthcare utilisation and costs in the last 12 months of life including hospital-based activities and primary care.Results Healthcare utilisation and costs increased sharply in the last month of life. Hospital costs were the largest cost elements and decreased with age (0.78, 95% CI: 0.73–0.72, p < 0.005 for age group 90+ compared to age 65–69 and increased substantially with comorbidity burden (2.2, 95% CI: 2.09–2.26, p < 0.005 for those with 7+ comorbidities compared to those with 1–3 comorbidities). The costs were highest for haematological cancers (1.45, 95% CI: 1.38–1.52, p < 0.005) and those living in the London region (1.10, 95% CI: 1.02–1.19, p < 0.005).Conclusions Healthcare in the last year of life for advanced cancer patients is costly and offers unclear value to patients and the healthcare system. Further research is needed to understand distinct cancer populations’ pathways and experiences before recommendations can be made about the most appropriate models of care.Subject terms: Cancer, Cancer     

Stereoselective Synthesis and Anticancer Activity of 2,6-Disubstituted trans-3-Methylidenetetrahydropyran-4-ones

In this report, we present efficient and stereoselective syntheses of 2,6-disubstituted trans-3-methylidenetetrahydropyran-4-ones and 2-(4-methoxyphenyl)-5-methylidenetetrahydropyran-4-one that significantly broaden the spectrum of the available methylidenetetrahydropyran-4-ones with various substitution patterns. Target compounds were obtained using Horner–Wadsworth–Emmons methodology for the introduction of methylidene group onto the pyranone ring. 3-Diethoxyphosphoryltetrahydropyran-4-ones, which were key intermediates in this synthesis, were prepared by fully or highly stereoselective addition of Gilman or Grignard reagents to 3-diethoxyphosphoryldihydropyran-4-ones. Addition occurred preferentially by axial attack of the Michael donors on the dihydropyranone ring. Relative configurations and conformations of the obtained adducts were assigned using a detailed analysis of the NMR spectra. The obtained methylidenepyran-4-ones were evaluated for cytotoxic activity against two cancer cell lines (HL-60 and MCF-7). 2,6-Disubstituted 3-methylidenetetrahydropyran-4-ones with isopropyl and phenyl substituents in position 2 were more cytotoxic than analogs with n-butyl substituent. Two of the most cytotoxic analogs were then selected for further investigation on the HL-60 cell line. Both analogs induced morphological changes characteristic of apoptosis in cancer cells, significantly inhibited proliferation and induced apoptotic cell death. Both compounds also generated DNA damage, and one of the analogs arrested the cell cycle of HL-60 cells in the G2/M phase. In addition, both analogs were able to inhibit the activity of topoisomerase IIα. Based on these findings, the investigated analogs may be further optimized for the development of new and effective topoisomerase II inhibitors.     

The Use of Barley Malt as a Binder in Molding Sand Technology

The aim of this study was to attempt to use barley malt as a natural, organic binder in the technology of molding sand. TGA analysis of the binder was performed, during which temperatures of thermal decomposition of its components were determined. The results of TG/DTG analysis show that a loss of ~75% of mass of the MB binder is organic matter. Over 50% of this is starch. The results indicate the possibility of using a binder made of barley malt as a binding material for quartz sand grains. This fact was confirmed by tests carried out with use of SEM. During the observations, it was found that barley malt forms smooth bridges connecting individual grains of quartz sand. The typical properties of molding sands with barley malt were also determined, compared to sands containing commonly used binders. At the same time, the influence of the content of this binder on flowability, permeability, strength properties, and wear resistance was assessed. It has been found that increasing the binder content in molding mass results in an increase in strength and wear resistance, as opposed to flowability and permeability. Test castings were also made. It was found that the addition of a binder made of barley malt has a positive effect on the surface quality of castings. This was confirmed by roughness measurements of the test castings. At the same time, a tendency to excessive gas evolution during pouring was shown, with higher contents of this binder. Moreover, greater amounts of barley malt in the molding sand (MB 5%) as compared to the lower content (MB 2%) increased the thickness of the burnt layer of the sand by 25%. This is due to the exothermic reaction when more binder is burnt. It is extremely important from the point of view of the regeneration of molding sand.     

Rapid radiosynthesis of [11C] and [14C]azelaic,suberic, and sebacic acids for in vivo mechanistic studies of systemic acquired resistance in plants

A recent report that the aliphatic dicarboxylic acid, azelaic acid (1,9‐nonanedioic acid) but not related acids, suberic acid (1,8‐octanedioic acid) or sebacic (1,10‐decanedioic acid) acid induces systemic acquired resistance to invading pathogens in plants stimulated the development of a rapid method for labeling these dicarboxylic acids with ¹¹C and ¹⁴C for in vivo mechanistic studies in whole plants. ¹¹C‐labeling was performed by reaction of ammonium [¹¹C]cyanide with the corresponding bromonitrile precursor followed by hydrolysis with aqueous sodium hydroxide solution. Total synthesis time was 60 min. Median decay‐corrected radiochemical yield for [¹¹C]azelaic acid was 40% relative to trapped [¹¹C]cyanide, and specific activity was 15 GBq/µmol. Yields for [¹¹C]suberic and sebacic acids were similar. The ¹⁴C‐labeled version of azelaic acid was prepared from potassium [¹⁴C]cyanide in 45% overall radiochemical yield. Radiolabeling procedures were verified using ¹³C‐labeling coupled with ¹³C‐NMR and liquid chromatography–mass spectrometry analysis. The ¹¹C and ¹⁴C‐labeled azelaic acid and related dicarboxylic acids are expected to be of value in understanding the mode‐of‐action, transport, and fate of this putative signaling molecule in plants. Copyright © 2011 John Wiley & Sons, Ltd.     

The effect of hydrological connectivity on water beetles fauna in water bodies within the floodplain of a lowland river (Neman river, Belarus)

The middle course of the Neman River is the habitat of 120 water beetle species. Water beetles were most abundant in the Neman River, its major tributaries and oxbow lakes. They consisted of four synecological groups: rheobiontic and rheophilic organisms, type ??a?? and ??b?? stagnobionts. The diverse types of aquatic environments constitute faunal centers which, in addition to the specific and dominant Coleopteran populations, also feature migrational elements. The presence of close relations between the fauna of different environments indicates that they form a single, faunistically integrated hydrological system.     

Avian Feathers as Bioindicators of the Exposure to Heavy Metal Contamination of Food

The aim of this study was to determine the possibility of using feathers of blue tit nestlings to assess the level of endogenous accumulation of lead. For this purpose we conducted an experiment with lead application to randomly chosen nestlings from eight randomly drawn broods. Five days after the exposure, feathers of lead-treated nestlings had significantly higher lead concentrations than control nestlings. This result suggests that feathers can be used as reliable non-destructive bioindicators to assess the level of heavy metals originating from contaminated food, which is of great significance for comparative studies on ecological consequences of pollution.     

Towards the automatic computational assessment of enlarged perivascular spaces on brain magnetic resonance images: A systematic review

Enlarged perivascular spaces (EPVS), visible in brain MRI, are an important marker of small vessel disease and neuroinflammation. We systematically evaluated the literature up to June 2012 on possible methods for their computational assessment and analyzed confounds with lacunes and small white matter hyperintensities. We found six studies that assessed/identified EPVS computationally by seven different methods, and four studies that described techniques to automatically segment similar structures and are potentially suitable for EPVS segmentation. T2‐weighted MRI was the only sequence that identified all EPVS, but FLAIR and T1‐weighted images were useful in their differentiation. Inconsistency within the literature regarding their diameter and terminology, and overlap in shape, intensity, location, and size with lacunes, conspires against their differentiation and the accuracy and reproducibility of any computational segmentation technique. The most promising approach will need to combine various MR sequences and consider all these features for accurate EPVS determination. J. Magn. Reson. Imaging 2013;38:774–785. © 2013 Wiley Periodicals, Inc.     

The Leeds assessment scale of handicap: its operationalisation,reliability, validity and responsiveness in in-patient rehabilitation

Purpose : This paper describes the application of the handicap dimension of the International Classification of Impairments, Disabilities and Handicaps. Method : A method of assessing four of the six roles (or areas of expected competency) was developed and applied to an inpatient population, aged 16 to 65 years, receiving specialist rehabilitation following neurological damage. Handicap assessment was a collaborative process by a multidisciplinary team. Difficulties were experienced in measuring inter-rate reliability in the busy, clinical setting. Results : We conclude that handicap assessment in an in-patient rehabilitation unit which uses a multidisciplinary approach to treating patients with complex physical, sensory and cognitive problems is both feasible and useful. Conclusion : The developed scale, The Leeds Assessment Scale of Handicap, provides a valid and valuable summary of human disadvantage, complementing the common disability assessments.     

Enhanced Retroviral Transduction of 5-Fluorouracil-Resistant Human Bone Marrow (Stem) Cells Using a Genetically Modified Packaging Cell Line

Pluripotent hematopoietic stem cells (PHSC) are rare cells capableof multilineage differentiation, long-term reconstituting activity andextensive self-renewal. Such cells are the logical targets for manyforms of corrective gene therapy, but are poor targets for retroviralmediated gene transfer owing to their quiescence, as retroviraltransduction requires that the target cells be cycling. To try andsurmount this problem we have constructed a retroviral producer linethat expresses the membrane-bound form of human stem cell factor (SCF)on its cell surface. These cells are capable, therefore, of deliveringa growth signal concomitant with recombinant retroviral vectorparticles. In this report we describe the use of this cell line totransduce a highly quiescent population of cells isolated from adulthuman bone marrow using the 5-fluorouracil (FU) resistance technique ofBerardi et al. Quiescent cells selected using this technique weretransduced by cocultivation with retroviral producers expressingsurface bound SCF or with the parent cell line that does not. Followingcoculture, the cells were plated in long-term bone marrow culture for afurther 5 weeks, before plating the nonadherent cells in semisolidmedia. Colonies forming in the semisolid media over the next 14 dayswere analyzed by polymerase chain reaction for the presence of theretroviral vector genome. Over six experiments, the transductionfrequency of the quiescent 5-FU resistant cells using theSCF-expressing producer line averaged about 20%, whereas thosetransduced using the parent producer line showed evidence of reducedlevels or no transduction.