"How does public administration deal with a population that it perceives as diverse? Which ethnic differentiations are either produced by everyday concrete administra-tive actions or blurred in the ...sense of undoing ethnicity? Two intervening street-level bureaucracies are examined, a municipal youth welfare office and the police of a medium-sized town. The focus is on the close intertwining of ethnicizations with social work and with police categorizations and work practices. Ethnic attributions in social work and in police work can come into play when they are considered purposeful, opportune, helpful or effective in everyday work. At first glance, the official approach to ethnicity appears ambivalent and diffuse, and the intervention of the youth welfare office and the police in this regard appears intrans-parent and unpredictable. However, emphasizing or overlooking ethnic differences follows an instrumental logic, which can ultimately lead to the concealment or rein-forcement of state intervention. "
Search engines have become the most important medium for Internet users to find pages on the web. They help customers to decrease their information overload, and enhance the sales of commercial web ...sites in different ways. For these reasons, the exploration of and changes in (human) online searching behaviour has become a subject of particular importance. This paper will help search engine and web site administrators and developers to monitor online searching behaviour properly and to derive strategies from the information gained. We define standard parameters against which search engines can be measured and compared. These parameters also reflect the online searching behaviour of search engine users. Therefore, an overview of studies conducted in the last few years is given. Statistics used in different papers are compared to extract standard parameters for online searching behaviour. In the next step, search queries from four different search engines covering periods of between 10 and 13 months are compared using these parameters. Using an automatic process, we retrieved around 99% of all search queries from three different search engine live tickers. For the first time, different data sets over a long period are compared. We observe that some patterns stay stable in a number of different search engines, and shed light on patterns that shorter analyses could not adequately examine. Our observations do not support the assumption that web search has become more business driven. For this reason, we introduce the concept of evergreens in search queries. One implication is that search engines should simplify web search interfaces for users since Boolean operators and special search features are rarely used. We also present the evergreen topics in search queries.
Abstract The increasing incidence of BK-associated nephropathy following kidney transplantation has prompted an examination of strategies for risk reduction and management through immunosuppression ...manipulation. Evidence from retrospective and prospective studies suggests that BK viruria and viremia, and the need for BK virus treatment, are higher with tacrolimus than cyclosporine. Combined therapy with tacrolimus and mycophenolic acid may be associated with a particularly higher risk of BK infection, but data are conflicting as to whether mycophenolic acid per se is an independent risk factor. The incidence of BK-related events may be reduced in patients receiving mTOR inhibitors (everolimus or sirolimus) with cyclosporine vs a calcineurin inhibitor with mycophenolic acid. De novo immunosuppression regimens that avoid rabbit antithymocyte globulin and tacrolimus, particularly tacrolimus with mycophenolic acid, may be advantageous, whereas low-exposure cyclosporine with an mTOR inhibitor appears a favorable option. Routine screening for BK infection during the first 2 years posttransplant is recommended to allow preemptive modification of the immunosuppressive regimen. In patients at high risk of BK virus infection, appropriate de novo immunosuppression or very early conversion to an mTOR inhibitor to facilitate reduction or discontinuation of calcineurin inhibitors or antimetabolites should be considered. Extensive further research into optimal avoidance, screening, and treatment strategies is required.
The single nucleotide polymorphisms (SNPs) rs4794067, rs2275806, rs2232365, and rs3761548 map in the genes of TBX21, GATA3, and FOXP3 involved in mediating acute cellular rejection. We investigated ...whether these SNPs are associated with acute cellular liver transplant rejection. The SNPs were analyzed in recipients with early acute cellular rejection (n = 97), recipients with late acute cellular rejection (n = 49), and recipients without rejection (n = 149). There was no association between acute cellular rejection and SNPs rs4794067, rs2275806, and rs2232365. In contrast, the allele −3279A of FOXP3 SNP rs3761548 exhibited a higher frequency in recipients with late acute cellular rejection as compared with recipients without rejection. This result indicates that the allele −3279A of the SNP rs3761548 may predispose to the development of late acute cellular rejection.
Human leucocyte antigen G (HLA-G) is a non-classical HLA-class I antigen that exerts immunoregulatory functions. The polymorphisms 14-base pair (bp) insertion/deletion (ins/del) (rs1704) and ...+3142C > G (rs1063320) could modify the expression level of HLA-G.
We genotyped 175 kidney recipients (41 with acute rejection and 134 without rejection) and additionally the corresponding donors for both polymorphisms in order to assess their impact on acute rejections one year after transplantation. In addition, we analyzed soluble HLA-G (sHLA-G) levels in sera of 32 living kidney donors and compared the sHLA-G levels in terms of the present genotype.
In kidney transplant recipients we did not observe an impact of the 14-bp ins/ins and the +3142GG genotypes on acute rejection. In contrast, we found a higher frequency of these genotypes in the donors of the no-rejection collective compared to the rejection collective (4.9% vs. 24.6%; p = 0.010; 9.8% vs. 31.3%; p = 0.006). Soluble HLA-G levels were highest in healthy kidney donors homozygous for the 14-bp insertion.
We conclude that the HLA-G polymorphisms of the donor are of importance for susceptibility of acute rejection in kidney transplantation. We suggest that the 14-bp ins/ins and the +3142GG genotypes are protective against kidney transplant rejection.
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Background: Pleural (Pl) and pericardial (Pc) effusions are often encountered clinical problems in patients with lung cancer, contributing to a poor quality of life. ...Population-based data on predictors for Pl and Pc effusions in small cell lung cancer (SCLC) are scarce, particularly, in later lines. Methods: We estimated the predictors for treatment-emergent Pl and Pc effusions in SCLC patients treated with third-line of therapy (LOT) using Optum’s electronic health records (EHR) de-identified database. Of 8,291 patients with newly diagnosed SCLC between 01/01/2008 and 09/30/2016, 428 patients received 3
rd
LOT. Pc/Pl effusions were identified by a combination of ICD-9/ICD-10 codes, procedures, or natural language processing (NLP) SDS term and sentiment. Each patient contributed to follow-up time from start of 3
rd
LOT to the day prior to start of next LOT or earlier of (loss to follow-up date or 365 days from end of 3
rd
LOT) if there was no subsequent LOT, or first occurrence for those with an outcome event. Stepwise Cox regression with sle = 0.25 and sls = 0.10 was applied for variable selection. Results: At start of 3
rd
LOT, median age was 65, 46% were male, 97% had extensive disease (excluding n = 53 with missing staging). Cardiac history, pulmonary history, renal impairment (eGFR < 60 mL/min/1.73m
2
), prior Pl and Pc effusion, albumin levels below 3.5 g/dl, sodium levels below < 136 mmol/l, treatment regimens (others except platin-containing vs. topotecan mono) was each associated with increased risk of Pl effusions. Cardiac history, prior Pl and Pc effusion, and region (South vs. Midwest/West) was each associated with increased risk of Pc effusions. When the stepwise Cox regression was applied, cardiac history, prior Pl effusion, and treatment regimens were selected as significant predictors of Pl effusions (p < 0.05). Prior Pc effusion and cardiac history were selected as significant predictors of Pc effusion (p < 0.05). Conclusions: Awareness of the determinants associated with development of Pl and Pc effusions in SCLC patients treated in third-line therapy may aid in earlier recognition of patients at risk and lower the risk of developing Pl/Pc effusions in this group of patients.
The prognostic value of preformed donor-specific HLA antibodies (DSA), which are only detectable by sensitive methods, remains controversial for kidney transplantation.
The outcome of 4233 ...consecutive kidney transplants performed between 2012 and 2015 in 18 German transplant centers was evaluated. Most centers used a stepwise pretransplant antibody screening with bead array tests and differentiation of positive samples by single antigen assays. Using these screening results, DSA against HLA-A, -B, -C, -DRB1 and -DQB1 were determined. Data on clinical outcome and possible covariates were collected retrospectively.
Pretransplant DSA were associated with lower overall graft survival, with a hazard ratio of 2.53 for living donation (95% confidence interval 95% CI, 1.49 to 4.29;
0.001) and 1.59 for deceased donation (95% CI, 1.21 to 2.11;
=0.001). ABO-incompatible transplantation was associated with worse graft survival (hazard ratio, 2.09; 95% CI, 1.33 to 3.27;
=0.001) independent from DSA. There was no difference between DSA against class 1, class 2, or both. Stratification into DSA <3000 medium fluorescence intensity (MFI) and DSA ≥3000 MFI resulted in overlapping survival curves. Therefore, separate analyses were performed for 3-month and long-term graft survival. Although DSA <3000 MFI tended to be associated with both lower 3-month and long-term transplant survival in deceased donation, DSA ≥3000 MFI were only associated with worse long-term transplant survival in deceased donation. In living donation, only strong DSA were associated with reduced graft survival in the first 3 months, but both weak and strong DSA were associated with reduced long-term graft survival. A higher incidence of antibody-mediated rejection within 6 months was only associated with DSA ≥3000 MFI.
Preformed DSA were associated with an increased risk for graft loss in kidney transplantation, which was greater in living than in deceased donation. Even weak DSA <3000 MFI were associated with worse graft survival. This association was stronger in living than deceased donation.
The single nucleotide polymorphisms (SNPs) rs11188513, rs7071836, rs10748643, rs9450279, rs4458647, and rs6922 map in the genes of ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1) and ...5′‐nucleotidase ecto. We investigated whether these SNPs and haplotypes of these SNPs are associated with an acute cellular rejection after liver transplantation. A total of 69 recipients with an acute cellular rejection and 138 recipients without an acute cellular rejection were analyzed. Analyzed individually, no SNP demonstrates an association, but the haplotype rs11188513T‐rs7071836G‐rs10748643A of the ENTPD1 gene appeared more frequently in recipients without rejection and conversely, the haplotype rs11188513T‐rs7071836G‐rs10748643G of the ENTPD1 gene was more often represented in recipients with rejection. These two haplotypes seem to be important for the susceptibility of an acute cellular rejection after liver transplantation.
Over 100 putative driver genes that are associated with multiple recurrently altered pathways were detected in hepatocellular carcinoma (HCC), suggesting that multiple pathways will need to be ...inhibited for any therapeutic method to be effective. In this context, functional modification of the RNA regulating protein, tristetraprolin (TTP) that regulates approximately 2500 genes represents a promising strategy in HCC therapy. Since overexpression of TTP induces cell death in all cell types, it would be useful to target the regulator of TTP. In this study, we applied an inhibitor to MAPKAP2 (MK2) that suppresses TTP function. Importantly, cBIOportal for HCC genomics shows that expression level of the MK2 gene correlates with clinical outcome of HCC. We show that upon treatment with MK2 inhibitor, all 5 HCC cell lines, namely HepG2, Huh7, Hep3B, HLE and HLF, reduced cell growth, especially HepG2 and Hep3B cells underwent apoptosis. Simultaneously, TTP target genes such as c-Myc, IER3 or AKT-1 were downregulated. Depletion of the TTP gene rescued cells from apoptosis and restored the TTP-target mRNA expression in the presence of MK2 inhibitor. Furthermore, MK2 was activated in primary HCC that express TTP at high level. The TTP gene was induced upon treatment with DNA methylation inhibitor, 5-aza dC or interferon in three other cell lines, Huh7, HLE or HLF. Upon treatment with MK2 inhibitor and 5-aza dC or interferon these cells underwent apoptosis. The depletion of TTP in these cells partially rescued them from apoptosis, suggesting that the MK2/TTP pathway plays a role in proliferation and maintenance of HCCs. Notably, under the same conditions human hepatocyte cells (THLE-2) did not undergo apoptosis. These data also suggest that MK2 inhibitor with 5-aza dC or interferon may be a useful tool for therapy against HCC.
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