Abstract Introduction Prevalence of partial remission ranges between 20% and 80% in the initial course of type 1 diabetes. In this phase of the disease, a substantial insulin secretion contributes to ...good metabolic control. The aim of the study was to determine the association between presence of partial remission and occurrence of microangiopathy complications in type 1 diabetes. Material and Methods Ninety-eight consecutive patients with newly diagnosed type 1 diabetes were asked to participate in a cohort study. Partial remission was defined as the time in which all of the following criteria were met: HbA1c below 6.5% (48 mmol/mol), daily insulin requirement below 0.3 U/kg body weight and serum Cpeptide concentration above 0.5 ng/ml. Patients were divided into those who were in remission at any time during follow-up (remitters) and non-remitters. After 7 years of follow-up, the occurrence of microangiopathy complications was analyzed. In statistical analysis, Mann–Whitney test, chi2 test and Fisher test were used for analysis between groups. We applied a Cox's multivariate regression model and univariate regression method. P < 0.05 was considered statistically significant. Results In univariate logistic regression, a significant association was found between absence of remission and occurrence of at least one microvascular complication. In the Cox proportional hazards regression model that included clinically significant parameters at diagnosis (presence of ketoacidosis, cigarette smoking and HbA1c value) as covariates, absence of remission was associated with occurrence of chronic complications of diabetes at 7 years HR: 3.65 (95% CI 1.23–4.56), p = 0.04. In non-remitters, higher incidence of at least one microvascular complication (46.4% vs. 7.6%), higher incidence of retinopathy (42.8% vs. 5.7%), and neuropathy (21.4% vs. 1.9%) was found. Conclusions Occurrence of partial remission of diabetes is associated with a reduced risk of chronic microvascular complications at 7-year follow-up.
Herein, we report results from a genome-wide study conducted to identify protein quantitative trait loci (pQTL) for circulating angiogenic and inflammatory protein markers in patients with metastatic ...colorectal cancer (mCRC). The study was conducted using genotype, protein marker, and baseline clinical and demographic data from CALGB/SWOG 80405 (Alliance), a randomized phase III study designed to assess outcomes of adding VEGF or EGFR inhibitors to systemic chemotherapy in mCRC patients. Germline DNA derived from blood was genotyped on whole-genome array platforms. The abundance of protein markers was quantified using a multiplex enzyme-linked immunosorbent assay from plasma derived from peripheral venous blood collected at baseline. A robust rank-based method was used to assess the statistical significance of each variant and protein pair against a strict genome-wide level. A given pQTL was tested for validation in two external datasets of prostate (CALGB 90401) and pancreatic cancer (CALGB 80303) patients. Bioinformatics analyses were conducted to further establish biological bases for these findings. The final analysis was carried out based on data from 540,021 common typed genetic variants and 23 protein markers from 869 genetically estimated European patients with mCRC. Correcting for multiple testing, the analysis discovered a novel cis-pQTL in LINC02869, a long non-coding RNA gene, for circulating TGF-beta2 levels (rs11118119; AAF = 0.11; P-value < 1.4e-14). This finding was validated in a cohort of 538 prostate cancer patients from CALGB 90401 (AAF = 0.10, P-value < 3.3e-25). The analysis also validated a cis-pQTL we had previously reported for VEGF-A in advanced pancreatic cancer, and additionally identified trans-pQTLs for VEGF-R3, and cis-pQTLs for CD73. This study has provided evidence of a novel cis germline genetic variant that regulates circulating TGF-beta2 levels in plasma of patients with advanced mCRC and prostate cancer. Moreover, the validation of previously identified pQTLs for VEGF-A, CD73, and VEGF-R3, potentiates the validity of these associations.
The paper presents results of local performance analysis of a generalized adaptive notch filter (GANF). GANFs are used for identification/tracking of quasi-periodically varying dynamic systems and ...can be considered an extension, to the system case, of classical adaptive notch filters. The tracking properties of the algorithm are studied analytically using a direct averaging approach and an approximating linear filter technique. Even though restricted to a single-frequency case, the presented analysis provides valuable insights into the tracking mechanisms of GANF, including the associated speed/accuracy tradeoffs, the achievable performance bounds, and tracking limitations. In addition, it allows one to formulate some useful rules of thumb for choosing design parameters.
Using rational membrane protein design, we were recently able to obtain a β-barrel protein nanopore that was robust under an unusually broad range of experimental circumstances. This protein nanopore ...was based upon the native scaffold of the bacterial ferric hydroxamate uptake component A (FhuA) of Escherichia coli. In this work, we expanded the examinations of the open-state current of this engineered protein nanopore, also called FhuA ΔC/Δ4L, employing an array of lipid bilayer systems that contained charged and uncharged as well as conical and cylindrical lipids. Remarkably, systematical single-channel analysis of FhuA ΔC/Δ4L indicated that most of its biophysical features, such as the unitary conductance and the stability of the open-state current, were not altered under the conditions tested in this work. However, electrical recordings at high transmembrane potentials revealed that the presence of conical phospholipids within the bilayer catalyzes the first, stepwise current transition of the FhuA ΔC/Δ4L protein nanopore to a lower-conductance open state. This study reinforces the stability of the open-state current of the engineered FhuA ΔC/Δ4L protein nanopore under various experimental conditions, paving the way for further critical developments in biosensing and molecular biomedical diagnosis.
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► This paper shows the impact of lipid environment on a beta-barrel protein. ► This work demonstrates the unusual stability of the open-state current. ► Conical lipids catalyze the nanopore closure at greater transmembrane potentials.
Despite its ecological importance, little information is available regarding spatial and seasonal changes in the testate amoebae community in peat bogs. The objectives of this study were to examine ...the structure of communities and horizontal distribution of testate amoebae fauna, to improve the understanding of factors affecting the distribution of moss testate amoebae communities and to analyze the seasonal changes in testate amoebae communities in a Sphagnum-dominated peat bog (eastern Poland). A total of 45 testate amoebae species were identified in the samples. The highest species richness occurred in hollows dominated by
, much lower numbers of taxa were observed in hummocks dominated by
and
. The Monte Carlo permutation test showed the significance of N
, temperature, pH, and the depth to the water table for the variability of testate amoebae in all microhabitats. Species found in spring samples were associated with the increased N
content. Species occurring in summer samples were associated with the increasing pH gradient and species developing in late spring and autumn preferred a greater depth to the water table.
Previous literature on the consequences of decentralization has demonstrated a positive effect on voter participation in subnational elections. However, does this positive effect also extend to ...national level elections? This paper evaluates the consequences of decentralization-level political participation. Our approach innovates by disaggregating decentralization to uncover the specific dimensions that matter for voting participation. We argue that self-rule (or the authority that subnational units exercise in their own territory) is closely associated with vertical accountability and positively affects voting participation. Moreover, we find that political dimensions of self-rule matter more than fiscal dimensions. Shared-rule (or the authority that subnational units exercise in the country as a whole) has no significant effect on participation since it is more closely related to horizontal accountability. We test our theory in 20 Latin American and Caribbean countries using a hierarchical model with 2010 data at the national and individual-level.
•Measure how distinct components of regional authority affect national-level voting participation.•Disaggregating decentralization allows us to uncover dynamics typically obscured by aggregate measures.•Greater self-rule – a region's authority to elect representatives or tax – increases national-level voter turnout.•Political components of self-rule increase voting participation, while fiscal components have no significant effect.
Purpose After curative resection of gastric or gastroesophageal junction adenocarcinoma, Intergroup Trial 0116 (Phase III trial of postoperative adjuvant radiochemotherapy for high risk gastric and ...gastroesophageal junction adenocarcinoma: Demonstrated superior survival for patients who received postoperative chemoradiotherapy with bolus fluorouracil (FU) and leucovorin (LV) compared with surgery alone. CALGB 80101 (Alliance; Phase III Intergroup Trial of Adjuvant Chemoradiation After Resection of Gastric or Gastroesophageal Adenocarcinoma) assessed whether a postoperative chemoradiotherapy regimen that replaced FU plus LV with a potentially more active systemic therapy could further improve overall survival. Patients and Methods Between April 2002 and May 2009, 546 patients who had undergone a curative resection of stage IB through IV (M0) gastric or gastroesophageal junction adenocarcinoma were randomly assigned to receive either postoperative FU plus LV before and after combined FU and radiotherapy (FU plus LV arm) or postoperative epirubicin, cisplatin, and infusional FU (ECF) before and after combined FU and radiotherapy (ECF arm). Results With a median follow-up duration of 6.5 years, 5-year overall survival rates were 44% in the FU plus LV arm and 44% in the ECF arm ( P
= .69; multivariable hazard ratio, 0.98; 95% CI, 0.78 to 1.24 comparing ECF with FU plus LV). Five-year disease-free survival rates were 39% in the FU plus LV arm and 37% in the ECF arm ( P
= .94; multivariable hazard ratio, 0.96; 95% CI, 0.77 to 1.20). In post hoc analyses, the effect of treatment seemed to be similar across all examined patient subgroups. Conclusion After a curative resection of gastric or gastroesophageal junction adenocarcinoma, postoperative chemoradiotherapy using a multiagent regimen of ECF before and after radiotherapy does not improve survival compared with standard FU and LV before and after radiotherapy.
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