Establishing a colorectal cancer research database from routinely collected health data: the process and potential from a pilot study.

OBJECTIVE: Colorectal cancer is a common cause of death and morbidity. A significant amount of data are routinely collected during patient treatment, but they are not generally available for research. The National Institute for Health Research Health Informatics Collaborative in the UK is developing infrastructure to enable routinely collected data to be used for collaborative, cross-centre research. This paper presents an overview of the process for collating colorectal cancer data and explores the potential of using this data source. METHODS: Clinical data were collected from three pilot Trusts, standardised and collated. Not all data were collected in a readily extractable format for research. Natural language processing (NLP) was used to extract relevant information from pseudonymised imaging and histopathology reports. Combining data from many sources allowed reconstruction of longitudinal histories for each patient that could be presented graphically. RESULTS: Three pilot Trusts submitted data, covering 12 903 patients with a diagnosis of colorectal cancer since 2012, with NLP implemented for 4150 patients. Timelines showing individual patient longitudinal history can be grouped into common treatment patterns, visually presenting clusters and outliers for analysis. Difficulties and gaps in data sources have been identified and addressed. DISCUSSION: Algorithms for analysing routinely collected data from a wide range of sites and sources have been developed and refined to provide a rich data set that will be used to better understand the natural history, treatment variation and optimal management of colorectal cancer. CONCLUSION: The data set has great potential to facilitate research into colorectal cancer

Acyl-CoA synthetase 3 promotes lipid droplet biogenesis in ER microdomains

Control of lipid droplet (LD) nucleation and copy number are critical, yet poorly understood, processes. We use model peptides that shift from the endoplasmic reticulum (ER) to LDs in response to fatty acids to characterize the initial steps of LD formation occurring in lipid-starved cells. Initially, arriving lipids are rapidly packed in LDs that are resistant to starvation (pre-LDs). Pre-LDs are restricted ER microdomains with a stable core of neutral lipids. Subsequently, a first round of “emerging” LDs is nucleated, providing additional lipid storage capacity. Finally, in proportion to lipid concentration, new rounds of LDs progressively assemble. Confocal microscopy and electron tomography suggest that emerging LDs are nucleated in a limited number of ER microdomains after a synchronized stepwise process of protein gathering, lipid packaging, and recognition by Plin3 and Plin2. A comparative analysis demonstrates that the acyl-CoA synthetase 3 is recruited early to the assembly sites, where it is required for efficient LD nucleation and lipid storag

Contraceptive use among HIV-infected women and men receiving antiretroviral therapy in Lusaka, Zambia: a cross-sectional survey

Abstract Background Family planning (FP) is an essential health service and an important part of comprehensive HIV care. However, there is limited information about the contraceptive needs of people living with HIV in sub-Saharan Africa, which in turn has hampered efforts to expand and integrate FP services into existing HIV programs. Methods We performed a cross-sectional survey to determine FP prevalence and predictors among HIV-positive women and men attending 18 public antiretroviral therapy (ART) clinics in Lusaka, Zambia. Trained peer counselors administered the 10-question survey to those seeking care for five days at each of the target sites. Results From February to April 2014, we surveyed 7,046 HIV-infected patients receiving routine HIV services. Use of modern contraception was reported by 69 % of female ART patients and 79 % of male ART patients. However, highly effective contraceptive use and dual method use were low among women (38 and 25 %, respectively) and men (19 and 14 %, respectively). HIV disclosure status (adjusted odds ratio (AOR) = 4.91, 95 % confidence interval (CI) = 3.32–7.24 for women, AOR = 3.58, 95 % CI = 2.39–5.38 for men) and sexual activity in the last 6 months (AOR = 5.80, 95 % CI = 4.51–7.47 for women, AOR = 6.24, 95 % CI = 3.51–11.08 for men) were associated with modern contraceptive use in multivariable regression. Most respondents said they would access FP services if made available within ART clinic. Conclusions While FP-ART integration may be a promising strategy for increasing FP service uptake, such services must focus on assessing sexual activity and advocating for dual method use to increase effective contraceptive use and prevent unintended pregnancies

Ring formation in clonal plants

Ring shaped patches of clonal plants fascinated plant ecologists since long time. In this work we review the reports on the occurrence of ring pattern in different environmental conditions, the growth forms of ring-forming plants, the mechanisms underlying ring formation, and the consequences for species diversity at community scale. Rings formed by 83 species of clonal vascular plants have been found in grasslands, deserts, bare substrates of lava flow, harvested peat lands, salt marshes, and sand dunes. Four causal hypotheses have been proposed for the emergence of ring patterns: i. occurrence of architectural constraints for ramets development; ii. induction by fire, drought, trampling or overgrazing; iii. nutrient and water depletion by competition inside the ring; and iv. onset of species-specific negative plant-soil feedback in the inner zone of the clone. Since almost all the available studies are observations of ring structure or modelling exercises, none of the putative mechanisms for ring formation emerged from the literature as either generally applicable or suitable for rejection. Therefore, long-term field experiments are needed to investigate the relative prevalence of different mechanisms in different environments. Ring formation bears important consequences at community scale, because ring forming plants often act as \u201cnurses\u201d, enhancing the recruitment and development of different plant species. In fact, ring establishment modifies above- and below-ground environmental conditions, providing specialized safe sites for beneficiaries in the inner zone of the clones. Such interspecific facilitation by ring forming plants, particularly in chronically stressed environments, contributes to increase plant species richness and can locally promote the successional dynamics

Novel Agents, Combinations and Sequences for the Treatment of Advanced Renal Cell Carcinoma: When is the Revolution Coming?

Biological agents, such as multikinase inhibitors and mammalian target of rapamycin (mTOR) inhibitors, have replaced immunotherapy as the standard of care for metastatic renal cell carcinoma (mRCC). Several clinical trials have been performed, aimed to identify new feasible therapeutic targets. AKT, PI3K, STAT3, NOTCH-1, \u3b15\u3b21-integrin, CD70 and G250 are just examples of these opening frontiers. Novel agents, combination and sequences are emerging from the 887 clinical studies presently in course in mRCC to optimize patient outcomes. This report not includes studies on chemotherapy, local approaches, immunotherapy, surgical trials and other categories, but provides an update on ongoing phase I, II and III trials and preliminary results on targeted agents, used alone, in sequences or in combination for mRCC

Inhibition of dimethyl sulfoxide-induced differentiation of Friend erythroleukemic cells by 5'-methylthioadenosine

5'-Methylthioadenosine is a sulfur-containing nucleoside derived from the metabolism of polyamines which is known to exert an antiproliferative effect on several cell systems in vitro, including the Friend leukemia cell system. We have investigated the role of 5'-methylthioadenosine on the dimethyl sulfoxide-induced differentiation of this system. At a concentration of 400 microM, the drug strongly inhibited (80%) the induced differentiation of Friend cells, and this effect was already observable at a concentration as low as 10 microM (36% inhibition), as evidenced by the benzidine staining procedure and by the dot-blot hybridization of globin mRNA with a human beta-globin probe. Similar results have been obtained by using 5'-S-isobutylthioadenosine, which is a synthetic structural analogue of 5'-methylthioadenosine. The block of differentiation produced by these nucleosides was not mediated by adenine (a catabolite of both molecules) and was not reverted by spermine or spermidine, the two polyamines whose synthesis is inhibited by 5'-methylthioadenosine. We report a decrease of the aminopropyltransferases activities (the enzymes responsible for 5'-methylthioadenosine biosynthesis) in dimethyl sulfoxide-treated Friend cells, which could lead to a decrease of the intracellular content of 5'-methylthioadenosine during the erythroid maturation of Friend cells. The results obtained are consistent with the hypothesis that 5'-methylthioadenosine may act as an endogenous regulator of Friend cell differentiation

Effect of age on hemoglobin levels and quality of life following treatment with epoetin alfa in cancer patients

A subgroup analysis comparing elderly (age > or =70 years; n=95) with younger (age <70 years; n=390) patients was performed on data from a prospective, multicenter, open-label study assessing the effects of once-weekly epoetin alfa 40,000 International Units (IU) for 16-20 weeks on hemoglobin (Hb) levels and quality of life (QoL) in anemic adult patients undergoing chemotherapy for solid tumors. There were significant increases in mean Hb levels at 4, 8, 12, 16-20 weeks in both age groups (p<0.0001), but no significant differences between groups (p=0.7). No significant difference was observed in terms of blood transfusion rates across the study between elderly and younger patients (3.2% vs 6.7%, p=0.2). Although QoL was lower in elderly patients at baseline, the relative percentage increases in QoL scores during treatment were similar for both age groups. Thus, once-weekly epoetin alfa was equally effective in treating chemotherapy-related anemia in elderly and younger adult patients, with similar tolerability