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Panel‐reactive antibodies are widely regarded as an important immunological risk factor for rejection and graft loss. The broadness of sensitization against HLAis most appropriately measured by the “calculated population‐reactive antibodies” (cPRA) value. In this study, we investigated whether cPRArepresent an immunological risk in times of sensitive and accurate determination of pretransplantation donor‐specific HLA antibodies (DSA). Five hundred twenty‐seven consecutive transplantations were divided into four groups: cPRA0% (n = 250), cPRA1–50% (n = 129), cPRA51–100% (n = 43), and DSA(n = 105). Patients without DSAwere considered as normal risk and received standard immunosuppression without T cell–depleting induction. Patients with DSAreceived an enhanced induction therapy and maintenance immunosuppression. Surveillance biopsies were performed at 3 and 6 months. Median follow‐up was 5.7 years. Among the three cPRAgroups, there were no differences regarding the 1‐year incidence of ABMR(p = 0.16) and TCMR (p = 0.75). The 5‐year allograft survival rates were similar and around 87% (p = 0.28). The estimated glomerular filtration rateat last follow‐up was 50–53 mL/min (p = 0.45). On multivariable Cox proportional hazard analysis, the strongest independent predictor for ABMRand (death‐censored) graft survival was pretransplantation DSA. cPRAwere not predictive for ABMR,TCMR, or (death‐censored) graft survival. We conclude that with current DSAassignment, the broadness of sensitization measured by cPRAdoes not imply an immunological risk. This study investigates the impact of the broadness of sensitization measured by calculated population‐reactive antibodies on pertinent outcomes, and challenges its use as an immunological risk factor in renal allograft recipients.

Panel-reactive antibodies are widely regarded as an important immunological risk factor for rejection and graft loss. The broadness of sensitization against HLA is most appropriately measured by the “calculated population-reactive antibodies” (cPRA) value. In this study, we investigated whether cPRA represent an immunological risk in times of sensitive and accurate determination of pretransplantation donor-specific HLA antibodies (DSA). Five hundred twenty-seven consecutive transplantations were divided into four groups: cPRA 0% (n = 250), cPRA 1–50% (n = 129), cPRA 51–100% (n = 43), and DSA (n = 105). Patients without DSA were considered as normal risk and received standard immunosuppression without T cell–depleting induction. Patients with DSA received an enhanced induction therapy and maintenance immunosuppression. Surveillance biopsies were performed at 3 and 6 months. Median follow-up was 5.7 years. Among the three cPRA groups, there were no differences regarding the 1-year incidence of ABMR (p = 0.16) and TCMR (p = 0.75). The 5-year allograft survival rates were similar and around 87% (p = 0.28). The estimated glomerular filtration rate at last follow-up was 50–53 mL/min (p = 0.45). On multivariable Cox proportional hazard analysis, the strongest independent predictor for ABMR and (death-censored) graft survival was pretransplantation DSA. cPRA were not predictive for ABMR, TCMR, or (death-censored) graft survival. We conclude that with current DSA assignment, the broadness of sensitization measured by cPRA does not imply an immunological risk.

Metabolic syndrome after transplantation is a major concern following solid organ transplantation (SOT). The CREB-regulated transcription co-activator 2 (CRTC2) regulates glucose metabolism. The effect of CRTC2polymorphisms on new-onset diabetes after transplantation (NODAT) was investigated in a discovery sample of SOT recipients (n1=197). Positive results were tested for replication in two samples from the Swiss Transplant Cohort Study (STCS, n2=1294 and n3=759). Obesity and other metabolic traits were also tested. Associations with metabolic traits in population-based samples (n4=46’186, n5=123’865, n6>100,000) were finally analyzed. In the discovery sample, CRTC2 rs8450-AAgenotype was associated with NODAT, fasting blood glucose and body mass index (Pcorrected<0.05). CRTC2 rs8450-AAgenotype was associated with NODAT in the second STCS replication sample (odd ratio (OR)=2.01, P=0.04). In the combined STCS replication samples, the effect of rs8450-AAgenotype on NODAT was observed in patients having received SOT from a deceased donor and treated with tacrolimus (n=395, OR=2.08, P=0.02) and in non-kidney transplant recipients (OR=2.09, P=0.02). Moreover, rs8450-AAgenotype was associated with overweight or obesity (n=1215, OR=1.56, P=0.02), new-onset hyperlipidemia (n=1007, OR=1.76, P=0.007), and lower high-density lipoprotein-cholesterol (n=1214, β=-0.08, P=0.001). In the population-based samples, a proxy of rs8450G>Awas significantly associated with several metabolic abnormalities. CRTC2 rs8450G>Aappears to have an important role in the high prevalence of metabolic traits observed in patients with SOT. A weak association with metabolic traits was also observed in the population-based samples.

Organ-transplant-recipients exhibit cancerization of the skin from which multiple human papillomavirus (HPV)-positive squamous cell carcinomas (SCCs) arise. However, the molecular basis for HPV-induced invasion of skin keratinocytes is not known. We generated a transgenic mouse model expressing the E7 oncoprotein of HPV8 in the murine epidermis under the control of the keratin-14 promoter and showed that E7 is carcinogenic in mice. We further showed that both, the E7-expressing keratinocyte and mesenchymal components of the extracellular matrix as critical in eliciting the invasive behavior. E7 expression in basal keratinocytes, grown on fibronectin, led to epithelial–mesenchymal transition mediated by a cadherin switch. E7-positive keratinocytes displayed enhanced EDA-fibronectin expression and secretion and stimulated dermal fibroblasts to express EDA-fibronectin. Deposition of fibronectin was also detected in the peritumoral stroma of HPV8-positive skin SCC. When grown on fibronectin, E7-positive keratinocytes, in particular stem cell-like cells, exhibited increased cell surface levels of the α3-integrin chain. Functional blocking confirmed α3 as a critical molecule sufficient to induce E7-mediated invasion. This mechanistic link is further supported by expression of an E7-mutant, impaired in targeting α3 to the cell surface. These findings highlight the importance of epithelial–extracellular matrix interaction required for keratinocyte invasion and provide further mechanistic evidence for a role of HPV in skin carcinogenesis.

Most countries exclude human immunodeficiency virus (HIV)‐positive patients from organ donation because of concerns regarding donor‐derived HIVtransmission. The Swiss Federal Act on Transplantation has allowed organ transplantation between HIV‐positive donors and recipients since 2007. We report the successful liver transplantation from an HIV‐positive donor to an HIV‐positive recipient. Both donor and recipient had been treated for many years with antiretroviral therapy and harbored multidrug‐resistant viruses. Five months after transplantation, HIVviremia remains undetectable. This observation supports the inclusion of appropriate HIV‐positive donors for transplants specifically allocated to HIV‐positive recipients. The authors report the first liver transplant from an HIV‐positive donor to an HIV‐positive recipient with a successful outcome at 6 months, and argue that the medical and social advances represented by this case call for legal and political progress. See the editorial from Fishman and Feng on page 2252.

A palaeoenvironmental study of a palaeochannel within the lower alluvial floodplain of the Allier River, France, has been carried out at a high temporal resolution. Research was based upon a multi-proxy approach using different sedimentological (magnetic susceptibility, sediment texture and loss on ignition) and palaeoecological (pollen, non-pollen palynomorphs (NPPs), diatoms – indicators). The palaeochannel was dated from six radiocarbon dates and spans from the second to the eleventh century AD. The cultural landscape history of this floodplain and the progressive hydrological disconnection of the palaeochannel between the Antiquity and the early Middle Ages could be reconstructed according to several characteristic environmental phases. Co-inertia analysis linking pollen, NPPs and diatom corroborated the significant co-structure of these proxies and allowed to distinguish functional palaeoecological groups in terms of landscape openness, on-site aquatic and hygrophilous vegetation, riparian woodland, soil moisture and grazing pressure. Results obtained underpin the importance of grazing as a major agent of landscape change in floodplains, especially since the ninth century AD, when the clearance of the riparian woodland is attested. Gallo-Roman and Late-Antiquity land-use systems, on the contrary, allowed for the preservation of riparian fluvial landscapes.

Urinary CXCL10 is a promising noninvasive biomarker for tubulo‐interstitial allograft inflammation, but its diagnostic characteristics have not been assessed in a real‐life setting. We investigated urinary CXCL10 in 213 consecutive renal allograft recipients having 362 surveillance biopsies at 3/6 months and 80 indication biopsies within the first year posttransplant. Allograft histology results were classified as (i) acute Banff score zero, (ii) interstitial infiltrates only, (iii) tubulitis t1, (iv) tubulitis t2–3 and (v) isolated vascular compartment inflammation. For clinical and subclinical pathologies, urinary CXCL10 correlated well with the extent of tubulo‐interstitial inflammation. To determine diagnostic characteristics of urinary CXCL10, histological groups were separated into two categories: no relevant inflammation (i.e. acute Banff score zero and interstitial infiltrates only) versus all other pathologies (i.e. tubulitis t1–3 and isolated vascular compartment inflammation). For subclinical pathologies, AUC was 0.69 (sensitivity 61%, specificity 72%); for clinical pathologies, AUC was 0.74 (sensitivity 63%, specificity 80%). A urinary CXCL10‐guided biopsy strategy would have reduced performance of surveillance and indication biopsies by 61% and 64%, respectively. Missed (sub)clinical pathologies were mostly tubulitis t1 and isolated vascular compartment lesions. In real life, urinary CXCL10 had clinically useful diagnostic properties making it a candidate biomarker to guide allograft biopsies.

Urinary CXCL10 is a promising noninvasive biomarker for tubulo-interstitial allograft inflammation, but its diagnostic characteristics have not been assessed in a real-life setting. We investigated urinary CXCL10 in 213 consecutive renal allograft recipients having 362 surveillance biopsies at 3/6 months and 80 indication biopsies within the first year posttransplant. Allograft histology results were classified as (i) acute Banff score zero, (ii) interstitial infiltrates only, (iii) tubulitis t1, (iv) tubulitis t2–3 and (v) isolated vascular compartment inflammation. For clinical and subclinical pathologies, urinary CXCL10 correlated well with the extent of tubulo-interstitial inflammation. To determine diagnostic characteristics of urinary CXCL10, histological groups were separated into two categories: no relevant inflammation (i.e. acute Banff score zero and interstitial infiltrates only) versus all other pathologies (i.e. tubulitis t1–3 and isolated vascular compartment inflammation). For subclinical pathologies, AUC was 0.69 (sensitivity 61%, specificity 72%); for clinical pathologies, AUC was 0.74 (sensitivity 63%, specificity 80%). A urinary CXCL10-guided biopsy strategy would have reduced performance of surveillance and indication biopsies by 61% and 64%, respectively. Missed (sub)clinical pathologies were mostly tubulitis t1 and isolated vascular compartment lesions. In real life, urinary CXCL10 had clinically useful diagnostic properties making it a candidate biomarker to guide allograft biopsies.

Cytomegalovirus (CMV) infection is a common complication after organ transplantation. Previous studies have demonstrated that activating killer‐cell immunoglobulin‐like receptors (KIR) may reduce the rate of CMV infection. KIR genes can be divided into haplotype A (containing a fixed set of inhibitory receptors) and haplotype B (carrying additional activating KIR genes). The KIR locus is divided into a centromeric and a telomeric portion, both of which may carry A or B haplotype motifs. We studied a cohort of 339 kidney transplant recipients to elucidate which KIR genes protect from CMV infection. CMV infection occurred in 139 patients (41%). Possession of telomeric (hazard ratio 0.64, 95% confidence interval 0.44–0.94, p = 0.02) but not centromeric (HR 0.86, 95% CI 0.60–1.23, p = 0.41) B motifs was associated with statistically significant protection from CMV infection. Due to linkage disequilibrium, we were not able to identify a single protective gene within the telomeric B complex (which may contain the KIR2DS1, KIR3DS1, KIR2DL5A and KIR2DS5 genes). The presence of known or putative ligands to activating KIR did not significantly modify the influence of telomeric B group genes. We confirm that B haplotypes protect from CMV infection after kidney transplantation and show that this arises from telomeric B haplotype genes.

Cytomegalovirus (CMV) infection is a common complication after organ transplantation. Previous studies have demonstrated that activating killer-cell immunoglobulin-like receptors (KIR) may reduce the rate of CMV infection. KIR genes can be divided into haplotype A (containing a fixed set of inhibitory receptors) and haplotype B (carrying additional activating KIR genes). The KIR locus is divided into a centromeric and a telomeric portion, both of which may carry A or B haplotype motifs. We studied a cohort of 339 kidney transplant recipients to elucidate which KIR genes protect from CMV infection. CMV infection occurred in 139 patients (41%). Possession of telomeric (hazard ratio 0.64, 95% confidence interval 0.44–0.94, p = 0.02) but not centromeric (HR 0.86, 95% CI 0.60–1.23, p = 0.41) B motifs was associated with statistically significant protection from CMV infection. Due to linkage disequilibrium, we were not able to identify a single protective gene within the telomeric B complex (which may contain the KIR2DS1, KIR3DS1, KIR2DL5A and KIR2DS5 genes). The presence of known or putative ligands to activating KIR did not significantly modify the influence of telomeric B group genes. We confirm that B haplotypes protect from CMV infection after kidney transplantation and show that this arises from telomeric B haplotype genes.

Early detection of polyomavirus BK (BKV) viremia and reduction of immunosuppression is recommended for preventing polyomavirus‐associated nephropathy (PyVAN), but systematic histological evaluations were not performed in previous studies. We routinely screen for decoy cells and, if positive, measure plasma BKV‐loads. In a cohort of 203 consecutive renal transplantations performed from 2005–2008, 38 patients (19%) developed BKV‐viremia and were treated with reduction of immunosuppression. Based on subsequent allograft biopsy results and peak BKV‐viremia, patients were assigned to three groups: (i) definitive PyVAN (n = 13), (ii) presumptive PyVAN defined by plasma BKV‐loads of ≥4 log10copies/ml (n = 17) and (iii) low BKV‐viremia (n = 8). Clearance of BKV‐viremia was achieved in 35/38 patients (92%) and subsequent clinical rejection occurred in 3/35 patients (8.6%), both without any difference among the groups. Patients with definitive PyVAN had higher peak plasma BKV‐loads and required longer time for clearance (8.8 vs. 4.6 vs. 2.9 months; p = 0.001). However, allograft function remained stable from baseline to last follow‐up at 34 months (range 18–60) in all three groups with median serum creatinine of 1.6 mg/dl, 1.6 mg/dl and 1.3 mg/dl, respectively. We conclude that screening for BKV‐replication and reduction of immunosuppression is an effective strategy to preserve medium‐term allograft function even in patients developing definitive PyVAN.

Early detection of polyomavirus BK (BKV) viremia and reduction of immunosuppression is recommended for preventing polyomavirus-associated nephropathy (Py-VAN), but systematic histological evaluations were not performed in previous studies. We routinely screen for decoy cells and, if positive, measure plasma BKV-loads. In a cohort of 203 consecutive renal transplantations performed from 2005–2008, 38 patients (19%) developed BKV-viremia and were treated with reduction of immunosuppression. Based on subsequent allograft biopsy results and peak BKV-viremia, patients were assigned to three groups: (i) definitive PyVAN (n = 13), (ii) presumptive PyVAN defined by plasma BKV-loads of >4 log10 copies/ml (n = 17) and (iii) low BKV-viremia (n = 8). Clearance of BKV-viremia was achieved in 35/38 patients (92%) and subsequent clinical rejection occurred in 3/35 patients (8.6%), both without any difference among the groups. Patients with definitive PyVAN had higher peak plasma BKV-loads and required longer time for clearance (8.8 vs. 4.6 vs. 2.9 months; p = 0.001). However, allograft function remained stable from baseline to last follow-up at 34 months (range 1860) in all three groups with median serum creatinine of 1.6 mg/dl, 1.6 mg/dl and 1.3 mg/dl, respectively. We conclude that screening for BKV-replication and reduction of immunosuppression is an effective strategy to preserve medium-term allograft function even in patients developing definitive PyVAN.

Low-level donor-specific HLA-antibodies (HLA-DSA) (i.e. detectable by single-antigen flow beads, but negative by complement-dependent cytotoxicity crossmatch) represent a risk factor for early allograft rejection. The short-term efficacy of an induction regimen consisting of polyclonal anti-T-lymphocyte globulin (ATG) and intravenous immunoglobulins (IvIg) in patients with low-level HLA-DSA is unknown. In this study, we compared 67 patients with low-level HLA-DSA not having received ATGIvIg induction (historic control) with 37 patients, who received ATGIvIg induction. The two groups were equal regarding retransplants, HLA-matches, number and class of HLA-DSA. The overall incidence of clinicalsubclinical antibody-mediated rejection (AMR) was lower in the ATGIvIg than in the historic control group (38 vs. 55; p 0.03). This was driven by a significantly lower rate of clinical AMR (11 vs. 46; p 0.0002). Clinical T-cell-mediated rejection (TCR) was significantly lower in the ATGIvIg than in the historic control group (0 vs. 50; p < 0.0001). Within the first year, allograft loss due to AMR occurred in 7.5 in the historic control and in 0 in the ATGIvIg group. We conclude that in patients with low-level HLA-DSA, ATGIvIg induction significantly reduces TCR and the severity of AMR, but the high rate of subclinical AMR suggests an insufficient control of the humoral immune response.

Low‐level donor‐specific HLA‐antibodies (HLA‐DSA) (i.e. detectable by single‐antigen flow beads, but negative by complement‐dependent cytotoxicity crossmatch) represent a risk factor for early allograft rejection. The short‐term efficacy of an induction regimen consisting of polyclonal anti‐T‐lymphocyte globulin (ATG) and intravenous immunoglobulins (IvIg) in patients with low‐level HLA‐DSA is unknown. In this study, we compared 67 patients with low‐level HLA‐DSA not having received ATG/IvIg induction (historic control) with 37 patients, who received ATG/IvIg induction. The two groups were equal regarding retransplants, HLA‐matches, number and class of HLA‐DSA. The overall incidence of clinical/subclinical antibody‐mediated rejection (AMR) was lower in the ATG/IvIg than in the historic control group (38% vs. 55%; p = 0.03). This was driven by a significantly lower rate of clinical AMR (11% vs. 46%; p = 0.0002). Clinical T‐cell‐mediated rejection (TCR) was significantly lower in the ATG/IvIg than in the historic control group (0% vs. 50%; p < 0.0001). Within the first year, allograft loss due to AMR occurred in 7.5% in the historic control and in 0% in the ATG/IvIg group. We conclude that in patients with low‐level HLA‐DSA, ATG/IvIg induction significantly reduces TCR and the severity of AMR, but the high rate of subclinical AMR suggests an insufficient control of the humoral immune response.

Viral infection is a common complication after kidney transplantation. The role of natural killer cells (NK cells) in this setting remains unknown. NK cells express activating and inhibitory killer cell immunoglobulin-like receptors (KIR). We analyzed whether activating KIR genes carried by kidney transplant-recipients influence the rate of viral infection during the first year after transplantation. In patients with a KIR AA genotype (n 40, KIR2DS4 only activating KIR) the rate of cytomegalovirus (CMV) infection and reactivation was 36, as compared to 20 in transplant recipients with more than one activating KIR gene (KIR BX genotype, n 82, p 0.04). Adjusting for other risk factors in Cox regression, the relative risk of B versus A genotype patients was 0.34 (95 CI 0.15-0.76, p 0.009). The degree of protection increased with the number of activating KIR genes. Symptomatic CMV disease was only observed in four individuals, all carrying a KIR AA genotype. As for viral infections other than CMV, and for bacterial infections, no KIR-linked protective effect could be detected. Also, graft function and the rate-rejection episodes were similar in KIR AA and KIR BX genotype individuals. This study supports a role for activating KIR in the control of CMV infection after kidney transplantation.

Viral infection is a common complication after kidney transplantation. The role of natural killer cells (NK cells) in this setting remains unknown. NK cells express activating and inhibitory killer cell immunoglobulin-like receptors (KIR). We analyzed whether activating KIR genes carried by kidney transplant-recipients influence the rate of viral infection during the first year after transplantation. In patients with a KIR A/A genotype (n = 40, KIR2DS4 only activating KIR) the rate of cytomegalovirus (CMV) infection and reactivation was 36%, as compared to 20% in transplant recipients with more than one activating KIR gene (KIR B/X genotype, n = 82, p = 0.04). Adjusting for other risk factors in Cox regression, the relative risk of B versus A genotype patients was 0.34 (95% CI 0.15–0.76, p = 0.009). The degree of protection increased with the number of activating KIR genes. Symptomatic CMV disease was only observed in four individuals, all carrying a KIR A/A genotype. As for viral infections other than CMV, and for bacterial infections, no KIR-linked protective effect could be detected. Also, graft function and the rate-rejection episodes were similar in KIR A/A and KIR B/X genotype individuals. This study supports a role for activating KIR in the control of CMV infection after kidney transplantation.

Valid assessment of immunosuppressive therapy non-adherence (NAH) is vital: NAH is associated with negative transplantation outcomes. We studied the diagnostic accuracy of assay, patient self-reports and clinicians' collateral reports and composite adherence scores using electronic monitoring (EM) as a reference standard.

Valid assessment of immunosuppressive therapy non-adherence (NAH) is vital: NAH is associated with negative transplantation outcomes. We studied the diagnostic accuracy of assay, patient self-reports and clinicians’ collateral reports and composite adherence scores using electronic monitoring (EM) as a reference standard.

Polyomavirus BK (BKV) is the primary cause of polyomavirus-associated nephropathy (PVAN) in kidney transplant (KT) recipients. Using ELISpot assays, we compared the frequency of interferon-γ (IFN-γ) secreting peripheral blood mononuclear cells (PBMC) after stimulation with overlapping peptide pools covering BKV large T-antigen (LT) and VP1 capsid proteins (VP1). In 10 healthy donors, LT and VP1 responses were low with median 24 (range 15–95) and 25 (7–113) spot-forming units/106PBMC (SFU), respectively. In 42 KT patients with current or recent plasma BKV loads, median LT and VP1 responses of 29 (0–524) and 114 (0–1432) SFU were detected, respectively. In KT patients with decreasing or past plasma BKV loads, significantly higher median BKV-specific IFN-γ responses were detected compared to KT patients with increasing or persisting BKV loads [LT: 78 (8–524) vs. 22 (0–120) SFU, p = 0.003; VP1: 285 (45–1432) vs. 53 (0–423) SFU, p = 0.001, respectively]. VP1-specific IFN-γ responses were higher and more likely to involve CD4+T cells, while CD8+T cells were more frequently directed against LT. Stimulation with JCV-specific VP1 and LT peptides indicated only low-level cross-recognition. The data suggest that control of BKV replication is correlated with differentiated expansion of BKV-specific cellular immune responses.

Preformed donor-specific HLA-antibodies antibodies (DSA) are a major risk for early antibody-mediated rejection (AMR). This prospective study evaluated the accuracy of pretransplant risk assessment using virtual crossmatching (virtualXM) (i.e. comparing HLA-typing of the donor with the recipient’s HLA-antibody specificities determined by flow-beads). Sixty-five consecutive patients were stratified according to virtualXM results: patients without DSA (n= 56) were considered low risk and received standard immunosuppression; patients with DSA (n= 9) were considered high risk and received additional induction with anti-T-lymphocyte-globulin (ATG) and intravenous immunoglobulins. Despite induction therapy 4 of 9 patients with DSA (44%) had clinical/subclinical AMR, whereas only 2 of 56 patients without DSA (4%) (p = 0.002). Notably, one of these two patients had early AMR likely induced by non-HLA-antibodies; the other had subclinical AMR at month 6 consistent with de novoDSA. The results of virtualXM and retrospectively obtained flow-cytometric crossmatches (FCXM) (n= 59) were concordant in 51 patients (86%), four patients (7%) were virtualXM−/FCXM+ and none had AMR, four patients (7%) were virtualXM+/FCXM− and one had AMR. VirtualXM can accurately define absence or presence of DSA and may become an invaluable tool for organ allocation and pretransplant risk assessment. However, further studies need to address whether all HLA-antibodies detected by flow-beads are clinically relevant.

Non-adherence with immunosuppressive regimen is a major risk factor for poor outcome after kidney transplantation. Identifying patients at risk for non-adherence requires understanding the risk factors for non-adherence. This prospective study included a convenience sample of 249 adult kidney transplant patients >1 year post-transplant. Non-adherence was monitored electronically using MEMS®. Selected socio-economic, therapy-, patient-, condition- and healthcare team-related risk factors for non-adherence were assessed. Period prevalences were expressed as the percent of prescribed doses taken (taking adherence), the percent of correctly dosed days (dosing adherence), the percentage of inter-dose intervals not exceeding 25 of the prescribed interval (timing adherence), and the number of drug holidays per 100 days (no intake for > 48 h if once daily or for > 24 h if twice daily intake). Testing occurred by simple mixed logistic regression analysis. Factors significant after correction for multiple testing were entered into a multiple logistic regression model. Mean taking, dosing, timing adherence, and drug holidays were 98, 96, 93, and 1.1 days, respectively. Non-adherence was associated with lower self-efficacy, higher self-reported non-adherence, no pillbox usage, and male gender. Adherence declined between Monday and Sunday. This study provides a framework for identifying patients at risk for non-adherence and for developing adherence-enhancing interventions.

Non-adherence with immunosuppressive regimen is a major risk factor for poor outcome after kidney transplantation. Identifying patients at risk for non-adherence requires understanding the risk factors for non-adherence. This prospective study included a convenience sample of 249 adult kidney transplant patients >1 year post-transplant. Non-adherence was monitored electronically using MEMS®. Selected socio-economic, therapy-, patient-, condition- and healthcare team-related risk factors for non-adherence were assessed. Period prevalences were expressed as the percent of prescribed doses taken (taking adherence), the percent of correctly dosed days (dosing adherence), the percentage of inter-dose intervals not exceeding 25% of the prescribed interval (timing adherence), and the number of drug holidays per 100 days (no intake for > 48 h if once daily or for > 24 h if twice daily intake). Testing occurred by simple mixed logistic regression analysis. Factors significant after correction for multiple testing were entered into a multiple logistic regression model. Mean taking, dosing, timing adherence, and drug holidays were 98%, 96%, 93%, and 1.1 days, respectively. Non-adherence was associated with lower self-efficacy, higher self-reported non-adherence, no pillbox usage, and male gender. Adherence declined between Monday and Sunday. This study provides a framework for identifying patients at risk for non-adherence and for developing adherence-enhancing interventions.

Abstract: The genus Pinguicula(Lentibulariaceae) is unusual within the dicot order Lamiales because of the occurrence of both embryos with two cotyledons and those with just one cotyledon. In order to elucidate the infrageneric relationships and the evolutionary history of the embryo, we analysed (1) the internal transcribed spacers ITS1 and ITS2 of the nuclear ribosomal DNA (nrITS) of 29 Old and New World taxa of Pinguicula,and (2) the morphological and anatomical characters of the seeds. We suggest that the cotyledon number and spermoderm structure were quite unstable in the evolution of Pinguicula. Although basal nodes of the nrITS tree are sensitive to taxon sampling, all tree topologies found in this study imply homoplasy in the cotyledon number.

The genus PINGUICULA (Lentibulariaceae) is unusual within the dicot order Lamiales because of the occurrence of both embryos with two cotyledons and those with just one cotyledon. In order to elucidate the infrageneric relationships and the evolutionary history of the embryo, we analysed (1) the internal transcribed spacers ITS1 and ITS2 of the nuclear ribosomal DNA (nrITS) of 29 Old and New World taxa of PINGUICULA, and (2) the morphological and anatomical characters of the seeds. We suggest that the cotyledon number and spermoderm structure were quite unstable in the evolution of PINGUICULA. Although basal nodes of the nrITS tree are sensitive to taxon sampling, all tree topologies found in this study imply homoplasy in the cotyledon number.

Hydrogeomorphic processes within alluvial river systems create, maintain and degrade riparian habitat. The dynamic interactions between water, sediment, aquatic–terrestrial landforms and biotic elements control the functional processes and biodiversity patterns within the riparian zone and, thus, contribute directly to their ecological integrity and societal value. Numerous researchers from different disciplines publish work on the physical, biological, economic and societal functions of the riparian zone within various physiographic areas. The present paper aims to review the hydrogeomorphic processes of unconfined alluvial channel–floodplain rivers within the temperate zone. These processes and their interactions with the biotic environment provide the basis for understanding the physical as well as the ecological functioning of fluvial hydrosystems. The review focuses mainly on the European context, but major advances in riparian research from other continents are also considered. Rehabilitation and management strategies for the riparian zone are summarized and recommendations for further research conclude this review. Copyright © 2005 John Wiley & Sons, Ltd.

Fluvial processes of erosion, sediment transport and deposition determine the changing form and sedimentary structure of naturally adjusting riparian zones. Riparian sediment storage has both scientific and management importance in relation to: (i) the quantities of sediment that are involved; (ii) the quality of the sediment; and (iii) the dispersal of biological materials, notably the vegetation propagules that are transported and deposited in association with the sediment. After discussing the significance of riparian sedimentation processes, this paper reviews methods for quantifying contemporary sediment deposition within water bodies and their margins. Methods for investigating contemporary riparian sedimentation are given particular emphasis, and the extent to which different methods provide comparable estimates and have been used to support the analysis of different physical and chemical properties of the sediment are outlined. The importance of the following are stressed: (i) selecting a sampling method that is suited to the sedimentation environment; (ii) incorporating careful cross-calibration if measurements from different methods are to be combined; and (iii) replicating measurements to give more robust estimates if small traps are employed. It is concluded that artificial turf mats provide a useful design of sediment trap across a range of environmental conditions because: (i) their surface roughness reduces problems of sediment removal by flood waters or rainfall; (ii) their pliability permits installation on irregular surfaces; (iii) they can be securely attached to the ground with metal pins to resist high shear stresses from river flows; (iv) they are robust and light and so easily manipulated in the field and laboratory; (v) it is possible to fully recover the deposited sediment to accurately determine the amount of sediment deposited and to support a range of other analyses. Results are presented to illustrate how artificial turf mats can be used to estimate the quantity and quality of deposited sediment and to explore the associated deposition of viable seeds. This provides one example of the important hydroecological role of riparian sedimentation processes and of the potential for the development of innovative, interdisciplinary research on riparian sediment dynamics. Copyright © 2003 John Wiley & Sons, Ltd.

Fluvial processes of erosion, sediment transport and deposition determine the changing form and sedimentary structure of naturally adjusting riparian zones. Riparian sediment storage has both scientific and management importance in relation to: (i) the quantities of sediment that are involved; (ii) the quality of the sediment; and (iii) the dispersal of biological materials, notably the vegetation propagules that are transported and deposited in association with the sediment.

Trap states in organic single layer devices have been detected by the method of thermally stimulated currents (TSC). These devices have been exposed to potentially harmful atmospheres of oxygen and humid nitrogen in order to investigate the influence of ambient atmosphere on the trap spectrum of materials used for organic light-emitting diodes. Discrete traps with activation energies of 105 and 140meV have been found in α-NPD (N,N′-di(1-naphthyl)-N,N′-diphenylbenzidin). In 1-NaphDATA (4,4′,4″-Tris(N-2-naphthyl)-N-phenylamino-triphenylamin) discrete trap levels with activation energies of 100 and 235meV are present. The exposure to humidity forms a deep hole trap of 0.5eV in 1-NaphDATA, whereas in α-NPD no new trap was detected. The influence of the so generated traps on the charge transport is demonstrated by I–Vcharacteristics.

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Electron transfer from H2to Th79+was studied in a cryogenic Penning trap by non-destructively observing the sequential development with time of the charge state of one or a few stored particles. The ratio of the true double capture cross section to the total capture cross section was found to be 0.21 ± 0.11 at a mean center-of-mass energy near 6 eV.

Rodents prenatally exposed to ethanol demonstrate hypothalamic‐pituitary‐adrenal and behavioral hyperactivity to a variety of stressful situations. The present study examined both behavioral and corticosterone (CORT) responses to the elevated plus maze (+‐maze), an anxiety‐ or fear‐provoking task. Sprague‐Dawley male and female offspring from fetal ethanol‐exposed (E), pair‐fed (PF), and ad libitum‐fed control (C) groups were tested at 60 to 90 days of age. In experiment 1, behavior was measured in animals exposed to the +‐maze for 5 min on two consecutive days; 2 weeks later, both behavioral and CORT responses were measured in animals confined to the open and closed arms of the maze for 20 min. In experiment 2, animals were placed in an open field (OF) for 5 min before a single 5‐min exposure to the +‐maze. Factor analysis of the scored behaviors from the two experiments indicated two main factors, designated “exploration” and “fear.” E males and females both exhibited higher levels of exploratory behaviors when placed directly on the +‐maze from their homecages without prior exposure to the OF, compared with C males and females. In addition, when confined to the closed arms of the +‐maze, E males and females demonstrated higher levels of activity, compared with C males and females. After OF exposure, however, both E males and females demonstrated lower levels of exploratory behaviors than C males and females, and E females also had increased CORT levels, compared with PF and C females. Interestingly, E females, but not E males, showed an increase in fear‐related behaviors on the +‐maze, compared with controls, regardless of prior OF exposure. These data demonstrate that prenatal ethanol exposure may differentially affect both behavioral and hormonal responses of males and females in an aversive behavioral task and suggest that there may be a sex difference in the sensitivity of the mechanism(s) underlying these responses.

Thin films with layer sequences Nb/Hf/Nb and Nb/Ti/Nb/Au were prepared by electron-beam evaporation in ultrahigh vacuum. The interfaces were characterized by measuring the momentary surface properties by low energy electron diffraction and Auger electron spectroscopy after various evaporation steps. The Nb/Ti films were also investigated by Rutherford backscattering spectroscopy. Hydrogen charging was performed electrolytically or by implantation for Nb/Hf and Nb/Ti respectively. Hydrogen depth profiles were measured by the 15N nuclear reaction method. In the Nb/Hf films prepared at room temperature we found a strong accumulation of hydrogen in the hafnium layer. Owing to the high substrate temperature during evaporation, the Nb/Ti films showed some intermixing. In these films, hydrogen was almost equally distributed over the Nb/Ti/Nb layers. The out-diffusion of hydrogen through the gold layer started between 250 and 300 °C.

The hydrogen concentration in Nb films in equilibrium with an external H2-gas was measured by the 15N-NRA method using a differential pumping system. We find that the hydrogen solubility in films is reduced compared to that of bulk samples. This can be explained by the clamping of epitaxial films to the substrate. These first direct measurements of solubility curves for films are in disagreement with earlier investigations by other authors, who found — based on indirect concentration determinations — an increased solubility in films. We think that the discrepancy is due to incorrect concentration determinations in these earlier studies.

A vacuum toroidal field has been superimposed on a spheromak by means of an axial conductor. It has been observed that the resulting configuration corresponds to a tokamak with limiting low aspect ratio, i.e. a spherical torus with aspect ratio 1.1. The corresponding spheromak is unstable to n = 1 tilt and shift modes, but this tokamak configuration is found to be globally stable without additional passive stabilization.

Zusammenfassung Unter unseren 1112 Heilstättenpatienten im gesamten konnten wir in 2,1%, bei 418 Tuberkulösen mit offener Lungenerkrankung in 2,8% eine Nierentbc. diagnostizieren.

Unsatisfactory results are often yielded by the vacuum-melt extraction method for the rapid determination of nitrogen in steels. It has been ascertained that the nitrogen values obtained for steels containing Al, Ti and Zr are too low, and that they are increasingly on the low side as the carbon content in the extraction melt increases.

Prevalence of hypertension (HTN) is high after solid organ transplantation (SOT) and has been associated to graft failure, death-censored graft failure and death. The Swiss Transplant Cohort Study has enrolled SOT participants prospectively since 2008. No data on the prevalence of HTN and poorly controlled HTN has been reported from this cohort so far. The objective was therefore to determine the prevalence of HTN and poorly controlled HRN