Konjunkturpaket II: Was bringen Investitionen in Infrastruktur?

Die Bundesregierung hat mit dem sog. "Konjunkturpaket II" auf die Wirtschaftskrise reagiert und stellt insgesamt fast 50 Mrd. € zur Verfügung. Die Mittel sollen großenteils für Investitionen in Infrastruktur genutzt werden. Ulrich Klüh und Wolfgang Wiegard, Sachverständigenrat zur Begutachtung der gesamtwirtschaftlichen Entwicklung und Universität Regensburg, sehen die Bundesregierung mit den beschlossenen Maßnahmenpaketen auf dem richtigen Weg. Insgesamt seien die Maßnahmen zu befürworten. Kritisch zu sehen sei, dass ein erheblicher Teil der beschlossenen Maßnahmen erst im Jahr 2010 nachfragewirksam werde. Der mit den Konjunkturpaketen einhergehende Anstieg der Nettokreditaufnahme müsse aber, sobald die aktuelle Abschwungsphase vorbei sei, gestoppt und der Anstieg der staatlichen Schuldenstandsquote in den Folgejahren zurückgeführt werden. Auch Karl-Hans Hartwig, Universität Münster, begrüßt die Aufnahme von Verkehrsinfrastrukturinvestitionen in die Konjunkturpakete. Um die Investitionsmittel möglichst zielführend einzusetzen, sollten die für die Bundesverkehrswege vorgesehenen Gelder vorwiegend in die Substanzerhaltung und den Ausbau fließen. Thomas Bauer, Bayerischer Bauindustrieverband, sieht im Konjunkturprogramm II die Chance, in diesem und im kommenden Jahr Produktion und Beschäftigung in der deutschen Bauwirtschaft zu stabilisieren und die erwarteten Rückgänge speziell im Wirtschaftsbau und im Wohnungsbau zu einem erheblichen Teil zu kompensieren. Busso Grabow, Deutsches Busso Grabow, Deutsches Institut für Urbanistik, Berlin, unterstreicht, dass im Gegensatz zum ersten Paket das Konjunkturpaket II eine stärkere kommunale Komponente hat, so dass deutlich mehr Mittel auch dort ankommen, "wo sie für Menschen und Wirtschaft durch Verbesserungen im direkten Lebens- und Standortumfeld spürbar werden". Effekte des Konjunkturpakets im investiven Bereich könnten aber nur dann eintreten, wenn die Kommunen selbst flankierende Maßnahmen ergreifen könnte.Infrastrukturinvestition, Konjunktur, Wirtschaftskrise, Verkehrsinfrastruktur, Kommunale Infrastruktur, Deutschland

Antimicrobial Peptide Human Neutrophil Peptide 1 as a Potential Link Between Chronic Inflammation and Ductal Adenocarcinoma of the Pancreas

Objectives Defensins are antimicrobial peptides playing a role in innate immunity, in epithelial cell regeneration, and in carcinogenesis of inflammation-triggered malignancies. We analyzed this role in pancreatic ductal adenocarcinoma (PDAC) in the context of its association with chronic pancreatitis (CP). Methods Human tissue of healthy pancreas, CP, and PDAC was screened for defensins by immunohistochemistry. Defensin 1 (human neutrophil peptide 1 [HNP-1]) expression was validated using mass spectrometry and microarray analysis. Human neutrophil peptide 1 expression and influences of proinflammatory cytokines (tumor necrosis factor , interleukin 1, and interferon ) were studied in human pancreatic cancer cells (Colo 357, T3M4, PANC-1) and normal human pancreatic duct epithelial cells (HPDE). Results Accumulation of HNP-1 in malignant pancreatic ductal epithelia was seen. Spectrometry showed increased expression of HNP-1 in CP and even more in PDAC. At RNA level, no significant regulation was found. In cancer cells, HNP-1 expression was significantly higher than in HPDE. Proinflammatory cytokines significantly led to increased HNP-1 levels in culture supernatants and decreased levels in lysates of cancer cells. In HPDE cytokines significantly decreased HNP-1 levels. Conclusions Inflammatory regulation of HNP-1 in PDAC tissue and cells indicates that HNP-1 may be a link between chronic inflammation and malignant transformation in the pancreas

Autoimmunity-Related Risk Variants in PTPN22 and CTLA4 Are Associated With ME/CFS With Infectious Onset

Single nucleotide polymorphisms (SNP) in various genes have been described to be associated with susceptibility to autoimmune disease. In this study, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients and controls were genotyped for five immune gene SNPs in tyrosine phosphatase non-receptor type 22 (PTPN22, rs2476601), cytotoxic T-lymphocyte-associated protein 4 (CTLA4, rs3087243), tumor necrosis factor (TNF, rs1800629 and rs1799724), and interferon regulatory factor 5 (IRF5, rs3807306), which are among the most important risk variants for autoimmune diseases. Analysis of 305 ME/CFS patients and 201 healthy controls showed significant associations of the PTPN22 rs2476601 and CTLA4 rs3087243 autoimmunity-risk alleles with ME/CFS. The associations were only found in ME/CFS patients, who reported an acute onset of disease with an infection (PTPN22 rs2476601: OR 1.63, CI 1.04-2.55, p = 0.016; CTLA4 rs3087243: OR 1.53, CI 1.17-2.03, p = 0.001), but not in ME/CFS patients without infection-triggered onset (PTPN22 rs2476601: OR 1.09, CI 0.56-2.14, p = 0.398; CTLA4 rs3087243: OR 0.89, CI 0.61-1.30, p = 0.268). This finding provides evidence that autoimmunity might play a role in ME/CFS with an infection-triggered onset. Both genes play a key role in regulating B and T cell activation

PROGRESS – prospective observational study on hospitalized community acquired pneumonia

Background: Community acquired pneumonia (CAP) is a high incidence disease resulting in about 260,000 hospital admissions per year in Germany, more than myocardial infarction or stroke. Worldwide, CAP is the most frequent infectious disease with high lethality ranging from 1.2 % in those 20–29 years old to over 10 % in patients older than 70 years, even in industrial nations. CAP poses numerous medical challenges, which the PROGRESS (Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis) network aims to tackle: Operationalization of disease severity throughout the course of disease, outcome prediction for hospitalized patients and prediction of transitions from uncomplicated CAP to severe CAP, and finally, to CAP with sepsis and organ failure as a life-threatening condition. It is a major aim of PROGRESS to understand and predict patient heterogeneity regarding outcome in the hospital and to develop novel treatment concepts. Methods: PROGRESS was designed as a clinical, observational, multi-center study of patients with CAP requiring hospitalization. More than 1600 patients selected for low burden of co-morbidities have been enrolled, aiming at a total of 3000. Course of disease, along with therapy, was closely monitored by daily assessments and long-term follow-up. Daily blood samples allow in depth molecular-genetic characterization of patients. We established a well-organized workflow for sample logistics and a comprehensive data management system to collect and manage data from more than 50 study centers in Germany and Austria. Samples are stored in a central biobank and clinical data are stored in a central data base which also integrates all data from molecular assessments. Discussion: With the PROGRESS study, we established a comprehensive data base of high quality clinical and molecular data allowing investigation of pressing research questions regarding CAP. In-depth molecular characterization will contribute to the discovery of disease mechanisms and establishment of diagnostic and predictive biomarkers. A strength of PROGRESS is the focus on younger patients with low burden of co-morbidities, allowing a more direct look at host biology with less confounding. As a resulting limitation, insights from PROGRESS will require validation in representative patient cohorts to assess clinical utility. Trial registration: The PROGRESS study was retrospectively registered on May 24th, 2016 with ClinicalTrials.gov: NCT0278201

Cerebellar and premotor activity during a non-fatiguing grip task reflects motor fatigue in relapsing-remitting multiple sclerosis

Fatigue is a common and highly disabling symptom of multiple sclerosis. Patients experience an effort-independent general subjective feeling of fatigue as well as excessive fatigability when engaging in physical or mental activity. Previous research using functional magnetic resonance imaging (fMRI) has revealed heterogeneous findings, but some evidence implicates the motor system. To identify brain correlates of fatigue, 44 mildly impaired patients with relapsing-remitting multiple sclerosis and 25 age- and gender-matched healthy controls underwent functional magnetic resonance imaging at 3 Tesla, while they performed alternating blocks of rest and a non-fatiguing precision grip task. We investigated neural correlates of fatigue using the motor subscore of Fatigue Scale for Motor and Cognitive Functions (FSMCMOTOR) using the bilateral motor cerebellum, putamen, and dorsal premotor cortex as regions of interest. Patients and healthy controls performed the grip force task equally well without being fatigued. In patients, task-related activity in lobule VI of right motor cerebellum changed in proportion with individual FSMCMOTOR scores. In right dorsal premotor cortex, linear increases in activity across consecutive task blocks scaled with individual FSMCMOTOR scores in healthy controls, but not in patients. In premotor and dorsomedial prefrontal areas, patients were impaired at upscaling task-related activity the more they were affected by motor fatigue. The results support the notion that increased sensorimotor processing in the cerebellum contributes to the experience of motor fatigue and fatigability in multiple sclerosis. Additionally, downscaling of motivational input or sensorimotor processing in prefrontal and premotor areas may constitute an additional pathophysiological factor

Seminal plasma as a source of prostate cancer peptide biomarker candidates for detection of indolent and advanced disease

Background:Extensive prostate specific antigen screening for prostate cancer generates a high number of unnecessary biopsies and over-treatment due to insufficient differentiation between indolent and aggressive tumours. We hypothesized that seminal plasma is a robust source of novel prostate cancer (PCa) biomarkers with the potential to improve primary diagnosis of and to distinguish advanced from indolent disease. <br>Methodology/Principal Findings: In an open-label case/control study 125 patients (70 PCa, 21 benign prostate hyperplasia, 25 chronic prostatitis, 9 healthy controls) were enrolled in 3 centres. Biomarker panels a) for PCa diagnosis (comparison of PCa patients versus benign controls) and b) for advanced disease (comparison of patients with post surgery Gleason score <7 versus Gleason score >>7) were sought. Independent cohorts were used for proteomic biomarker discovery and testing the performance of the identified biomarker profiles. Seminal plasma was profiled using capillary electrophoresis mass spectrometry. Pre-analytical stability and analytical precision of the proteome analysis were determined. Support vector machine learning was used for classification. Stepwise application of two biomarker signatures with 21 and 5 biomarkers provided 83% sensitivity and 67% specificity for PCa detection in a test set of samples. A panel of 11 biomarkers for advanced disease discriminated between patients with Gleason score 7 and organ-confined (<pT3a) or advanced (≥pT3a) disease with 80% sensitivity and 82% specificity in a preliminary validation setting. Seminal profiles showed excellent pre-analytical stability. Eight biomarkers were identified as fragments of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase​,prostatic acid phosphatase, stabilin-2, GTPase IMAP family member 6, semenogelin-1 and -2. Restricted sample size was the major limitation of the study.</br> <br>Conclusions/Significance: Seminal plasma represents a robust source of potential peptide makers for primary PCa diagnosis. Our findings warrant further prospective validation to confirm the diagnostic potential of identified seminal biomarker candidates.</br&gt

One-electron oxidation of [M(PtBu3)2] (M=Pd, Pt) : isolation of monomeric [Pd(PtBu3)2]+and redox-promoted C−H bond cyclometalation

Oxidation of zero-valent phosphine complexes [M(PtBu3)2] (M=Pd, Pt) has been investigated in 1,2-difluorobenzene solution using cyclic voltammetry and subsequently using the ferrocenium cation as a chemical redox agent. In the case of palladium, a mononuclear paramagnetic PdI derivative was readily isolated from solution and fully characterized (EPR, X-ray crystallography). While in situ electrochemical measurements are consistent with initial one-electron oxidation, the heavier congener undergoes C−H bond cyclometalation and ultimately affords the 14 valence-electron PtII complex [Pt(κ2PC-PtBu2CMe2CH2)(PtBu3)]+ with concomitant formation of [Pt(PtBu3)2H]+