Uppsala University

About: Uppsala University is a education organization based out in Uppsala, Sweden. It is known for research contribution in the topics: Population & Gene. The organization has 36485 authors who have published 107509 publications receiving 4220668 citations. The organization is also known as: Uppsala universitet & uu.se.

Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib the LAP07 randomized clinical trial

Abstract: Importance In locally advanced pancreatic cancer, the role of chemoradiotherapy is controversial and the efficacy of erlotinib is unknown. Objectives To assess whether chemoradiotherapy improves overall survival of patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine-based induction chemotherapy and to assess the effect of erlotinib on survival. Design, Setting, and Participants In LAP07, an international, open-label, phase 3 randomized trial, 449 patients were enrolled between 2008 and 2011. Follow-up ended in February 2013. Interventions In the first randomization, 223 patients received 1000 mg/m 2 weekly of gemcitabine alone and 219 patients received 1000 mg/m 2 of gemcitabine plus 100 mg/d of erlotinib. In the second randomization involving patients with progression-free disease after 4 months, 136 patients received 2 months of the same chemotherapy and 133 underwent chemoradiotherapy (54 Gy plus capecitabine). Main Outcomes and Measures The primary outcome was overall survival from the date of the first randomization. Secondary outcomes were the effect of erlotinib and quality assurance of radiotherapy on overall survival, progression-free survival of gemcitabine-erlotinib and erlotinib maintenance with gemcitabine alone at the second randomization, and toxic effects. Results A total of 442 of the 449 patients (232 men; median age, 63.3 years) enrolled underwent the first randomization. Of these, 269 underwent the second randomization. Interim analysis was performed when 221 patients died (109 in the chemoradiotherapy group and 112 in the chemotherapy group), reaching the early stopping boundaries for futility. With a median follow-up of 36.7 months, the median overall survival from the date of the first randomization was not significantly different between chemotherapy at 16.5 months (95% CI, 14.5-18.5 months) and chemoradiotherapy at 15.2 months (95% CI, 13.9-17.3 months; hazard ratio [HR], 1.03; 95% CI, 0.79-1.34; P = .83). Median overall survival from the date of the first randomization for the 223 patients receiving gemcitabine was 13.6 months (95% CI, 12.3-15.3 months) and was 11.9 months (95% CI, 10.4-13.5 months) for the 219 patients receiving gemcitabine plus erlotinib (HR, 1.19; 95% CI, 0.97-1.45; P = .09; 188 deaths vs 191 deaths). Chemoradiotherapy was associated with decreased local progression (32% vs 46%, P = .03) and no increase in grade 3 to 4 toxicity, except for nausea. Conclusions and Relevance In this open-label, randomized trial involving patients with locally advanced pancreatic cancer with disease controlled after 4 months of induction chemotherapy, there was no significant difference in overall survival with chemoradiotherapy compared with chemotherapy alone and there was no significant difference in overall survival with gemcitabine compared with gemcitabine plus erlotinib used as maintenance therapy. Trial Registration clinicaltrials.gov Identifier:NCT00634725

The role of small cells, coordinated multipoint, and massive MIMO in 5G

Abstract: 5G will have to support a multitude of new applications with a wide variety of requirements, including higher peak and user data rates, reduced latency, enhanced indoor coverage, increased number of devices, and so on. The expected traffic growth in 10 or more years from now can be satisfied by the combined use of more spectrum, higher spectral efficiency, and densification of cells. The focus of the present article is on advanced techniques for higher spectral efficiency and improved coverage for cell edge users. We propose a smart combination of small cells, joint transmission coordinated multipoint (JT CoMP), and massive MIMO to enhance the spectral efficiency with affordable complexity. We review recent achievements in the transition from theoretical to practical concepts and note future research directions. We show in measurements with macro-plus-smallcell scenarios that spectral efficiency can be improved by flexible clustering and efficient user selection, and that adaptive feedback compression is beneficial to reduce the overhead significantly. Moreover, we show in measurements that fast feedback reporting combined with advanced channel prediction are able to mitigate the impairment effects of JT CoMP.

Key Principles for User-Centred Systems Design

Abstract: The concept of user-centred systems design (UCSD) has no agreed upon definition. Consequently, there is a great variety in the ways it is applied, which may lead to poor quality and poor usability in the resulting systems, as well as misconceptions about the effectiveness of UCSD. The purpose of this paper is to propose a definition of UCSD. We have identified 12 key principles for the adoption of a user-centred development process, principles that are based on existing theory, as well as research in and experiences from a large number of software development projects. The initial set of principles were applied and evaluated in a case study and modified accordingly. These principles can be used to communicate the nature of UCSD, evaluate a development process or develop systems development processes that support a user-centred approach. We also suggest activity lists and some tools for applying UCSD.

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

Abstract: We identified rare coding variants associated with Alzheimer's disease in a three-stage case–control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10−4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10−8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10−10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10−10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10−14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein–protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

Enhanced NK cell activity in mice injected with interferon and interferon inducers

Abstract: NATURAL KILLER (NK) cells constitute a distinct subgroup of cells within the immune system1,2. They are found in the lymphoid organs of several species including man and are cytolytic on contact in short-term in vitro assays for several cell types, in particular tumour cells1–5. Although the level of NK cell activity is under genetic control6,7, several extraneous agents, including bacterial adjuvants, animal viruses and NK-sensitive tumour cells induce an increase in in vivo NK cell activity6–10. Several of these agents are also known to increase the resistance of mice to transplantable tumours. This effect may be mediated by NK cells, as a positive correlation exists between in vivo resistance to syngeneic tumours and the levels of NK cell activity in the individual mice11,12. Viruses as well as several immunoadjuvants are also inducers of interferon. Here we present evidence that interferon and interferon inducers markedly enhance NK cell activity in mice, and suggest that interferon may be the mediator by which many different agents increase NK cell activity in vivo.