Experimental evidence for the immediate impact of fertilization and irrigation upon the plant and invertebrate communities of mountain grasslands

The response of montane and subalpine hay meadow plant and arthropod communities to the application of liquid manure and aerial irrigation – two novel, rapidly spreading management practices – remains poorly understood, which hampers the formulation of best practice management recommendations for both hay production and biodiversity preservation. In these nutrient-poor mountain grasslands, a moderate management regime could enhance overall conditions for biodiversity. This study experimentally assessed, at the site scale, among low-input montane and subalpine meadows, the short-term effects (1 year) of a moderate intensification (slurry fertilization: 26.7–53.3 kg N·ha−1·year−1; irrigation with sprinklers: 20 mm·week−1; singly or combined together) on plant species richness, vegetation structure, hay production, and arthropod abundance and biomass in the inner European Alps (Valais, SW Switzerland). Results show that (1) montane and subalpine hay meadow ecological communities respond very rapidly to an intensification of management practices; (2) on a short-term basis, a moderate intensification of very low-input hay meadows has positive effects on plant species richness, vegetation structure, hay production, and arthropod abundance and biomass; (3) vegetation structure is likely to be the key factor limiting arthropod abundance and biomass. Our ongoing experiments will in the longer term identify which level of management intensity achieves an optimal balance between biodiversity and hay production.

The dual impact of gender and the influence of timing of parenthood on men’s and women’s career development: Longitudinal findings

This study investigated the impact of gender, the gender-related self-concept (agency and communion), and the timing of parenthood on objective career success of 1,015 highly educated professionals. Hypotheses derived from a dual-impact model of gender and career-related processes were tested in a 5-wave longitudinal study over a time span of 10 years starting with participants’ career entry. In line with our hypotheses we found that the communal component of the gender self-concept had an impact on parenthood, and the agentic component influenced work hours and objective career success (salary, status) of both women and men. Parenthood had a negative direct influence on women’s work hours and a negative indirect influence on women’s objective career success. Women who had their first child around career entry were relatively least successful over the observation period. Men’s career success was independent of parenthood. Sixty-five percent of variance in women’s career success and 33% of variance in men’s career success was explained by the factors analyzed here. Mothers with partners working full time reduced their work hours more than mothers with partners not working full time. A test for a possible reverse influence of career success on the decision to become a parent revealed no effect for men and equivocal effects for women. We conclude that the transition to parenthood still is a crucial factor for women’s career development both from an external gender perspective (expectations, gender roles) and from an internal perspective (gender-related self-concept).

Impact of sepsis on risk of postoperative arterial and venous thromboses: large prospective cohort study

OBJECTIVES To evaluate the impact of preoperative sepsis on risk of postoperative arterial and venous thromboses. DESIGN Prospective cohort study using the National Surgical Quality Improvement Program database of the American College of Surgeons (ACS-NSQIP). SETTING Inpatient and outpatient procedures in 374 hospitals of all types across the United States, 2005-12. PARTICIPANTS 2,305,380 adults who underwent surgical procedures. MAIN OUTCOME MEASURES Arterial thrombosis (myocardial infarction or stroke) and venous thrombosis (deep venous thrombosis or pulmonary embolism) in the 30 days after surgery. RESULTS Among all surgical procedures, patients with preoperative systemic inflammatory response syndrome or any sepsis had three times the odds of having an arterial or venous postoperative thrombosis (odds ratio 3.1, 95% confidence interval 3.0 to 3.1). The adjusted odds ratios were 2.7 (2.5 to 2.8) for arterial thrombosis and 3.3 (3.2 to 3.4) for venous thrombosis. The adjusted odds ratios for thrombosis were 2.5 (2.4 to 2.6) in patients with systemic inflammatory response syndrome, 3.3 (3.1 to 3.4) in patients with sepsis, and 5.7 (5.4 to 6.1) in patients with severe sepsis, compared with patients without any systemic inflammation. In patients with preoperative sepsis, both emergency and elective surgical procedures had a twofold increased odds of thrombosis. CONCLUSIONS Preoperative sepsis represents an important independent risk factor for both arterial and venous thromboses. The risk of thrombosis increases with the severity of the inflammatory response and is higher in both emergent and elective surgical procedures. Suspicion of thrombosis should be higher in patients with sepsis who undergo surgery.

Accumulation of FOXP3+T-cells in the tumor microenvironment is associated with an epithelial-mesenchymal-transition-type tumor budding phenotype and is an independent prognostic factor in surgically resected pancreatic ductal adenocarcinoma.

Here we explore the role of the interplay between host immune response and epithelial-mesenchymal-transition (EMT)-Type tumor-budding on the outcome of pancreatic adenocarcinoma (PDAC).CD4+, CD8+, and FOXP3+T-cells as well as iNOS+ (M1) and CD163+- macrophages (M2) were assessed on multipunch tissue-microarrays containing 120 well-characterized PDACs, precursor lesions (PanINs) and corresponding normal tissue. Counts were normalized for the percentage of tumor/spot and associated with the clinico-pathological features, including peritumoral (PTB) and intratumoral (ITB) EMT-Type tumor-budding and outcome.Increased FOXP3+T-cell-counts and CD163-macrophages and decreased CD8+T-cell-counts were observed in PDACs compared with normal tissues and PanINs (p < 0.0001). Increased peritumoral FOXP3+T-cell-counts correlated significantly with venous invasion, distant metastasis, R1-status, high-grade ITB, PTB and independently with reduced survival. Increased intratumoral FOXP3+T-cells correlated with lymphatic invasion, N1-stage, PTB and marginally with adverse outcome. High peritumoral CD163-counts correlated with venous invasion, PTB and ITB. High intratumoral CD163-counts correlated with higher T-stage and PTB.PDAC-microenvironment displays a tumor-favoring immune-cell composition especially in the immediate environment of the tumor-buds that promotes further growth and indicates a close interaction of the immune response with the EMT-process. Increased peritumoral FOXP3+T-cell density is identified as an independent adverse prognostic factor in PDAC. Patients with phenotypically aggressive PDACs may profit from targeted immunotherapy against FOXP3.

Acute pain therapy in German hospitals as competitive factor : Do competition, ownership and case severity influence the practice of acute pain therapy?

BACKGROUND Due to the implementation of the diagnosis-related groups (DRG) system, the competitive pressure on German hospitals increased. In this context it has been shown that acute pain management offers economic benefits for hospitals. The aim of this study was to analyze the impact of the competitive situation, the ownership and the economic resources required on structures and processes for acute pain management. MATERIAL AND METHODS A standardized questionnaire on structures and processes of acute pain management was mailed to the 885 directors of German departments of anesthesiology listed as members of the German Society of Anesthesiology and Intensive Care Medicine (DGAI, Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin). RESULTS For most hospitals a strong regional competition existed; however, this parameter affected neither the implementation of structures nor the recommended treatment processes for pain therapy. In contrast, a clear preference for hospitals in private ownership to use the benchmarking tool QUIPS (quality improvement in postoperative pain therapy) was found. These hospitals also presented information on coping with the management of pain in the corporate clinic mission statement more often and published information about the quality of acute pain management in the quality reports more frequently. No differences were found between hospitals with different forms of ownership in the implementation of acute pain services, quality circles, expert standard pain management and the implementation of recommended processes. Hospitals with a higher case mix index (CMI) had a certified acute pain management more often. The corporate mission statement of these hospitals also contained information on how to cope with pain, presentation of the quality of pain management in the quality report, implementation of quality circles and the implementation of the expert standard pain management more frequently. There were no differences in the frequency of using the benchmarking tool QUIPS or the implementation of recommended treatment processes with respect to the CMI. CONCLUSION In this survey no effect of the competitive situation of hospitals on acute pain management could be demonstrated. Private ownership and a higher CMI were more often associated with structures of acute pain management which were publicly accessible in terms of hospital marketing.

Impact of MET targeting on tumor-associated angiogenesis and growth of MET mutations-driven models of liver cancer

Deregulated expression of the MET receptor tyrosine kinase has been reported in up to 50% of patients with hepatocellular carcinoma, the most abundant form of liver cancers, and is associated with decreased survival. Consequently, MET is considered as a molecular target in this malignancy, whose progression is highly dependent on extensive angiogenesis. Here we studied the impact of MET small molecule inhibitors on angiogenesis-associated parameters and growth of xenograft liver models consisting of cells expressing MET-mutated variants M1268T and Y1248H, which exhibit constitutive kinase activity. We demonstrate that MET mutations expression is associated with significantly increased production of vascular endothelial growth factor, which is blocked by MET targeting only in cells expressing the M1268T inhibitor-sensitive but not in the Y1248H inhibitor-resistant variant. Decrease in vascular endothelial growth factor production is also associated with reduction of tyrosine phopshorylation of the vascular endothelial growth factor receptor 2 expressed on primary liver sinusoidal endothelial cells and with inhibition of vessel formation. Furthermore, MET inhibition demonstrated an efficient anti-tumor activity and considerable reduction in microvessel density only against the M1268T-derived intrahepatic tumors. Collectively, our data support the role of targeting MET-associated angiogenesis as a major biological determinant for liver tumor growth control.

The Phosphoinositide 3-Kinase p110α Isoform Regulates Leukemia Inhibitory Factor Receptor Expression via c-Myc and miR-125b to Promote Cell Proliferation in Medulloblastoma.

Medulloblastoma (MB) is the most common malignant brain tumor in childhood and represents the main cause of cancer-related death in this age group. The phosphoinositide 3-kinase (PI3K) pathway has been shown to play an important role in the regulation of medulloblastoma cell survival and proliferation, but the molecular mechanisms and downstream effectors underlying PI3K signaling still remain elusive. The impact of RNA interference (RNAi)-mediated silencing of PI3K isoforms p110α and p110δ on global gene expression was investigated by DNA microarray analysis in medulloblastoma cell lines. A subset of genes with selectively altered expression upon p110α silencing in comparison to silencing of the closely related p110δ isoform was revealed. Among these genes, the leukemia inhibitory factor receptor α (LIFR α) was validated as a novel p110α target in medulloblastoma. A network involving c-Myc and miR-125b was shown to be involved in the control of LIFRα expression downstream of p110α. Targeting the LIFRα by RNAi, or by using neutralizing reagents impaired medulloblastoma cell proliferation in vitro and induced a tumor volume reduction in vivo. An analysis of primary tumors revealed that LIFRα and p110α expression were elevated in the sonic hedgehog (SHH) subgroup of medulloblastoma, indicating its clinical relevance. Together, these data reveal a novel molecular signaling network, in which PI3K isoform p110α controls the expression of LIFRα via c-Myc and miR-125b to promote MB cell proliferation.

Immune regulatory and neuroprotective properties of preimplantation factor: From newborn to adult.

Embryonic-maternal interaction from the earliest stages of gestation has a key, sustained role in neurologic development, persisting into adulthood. Early adverse events may be detrimental in adulthood. Protective factors present during gestation could significantly impact post-natal therapy. The role of PreImplantation Factor (PIF) within this context is herein examined. Secreted by viable early embryos, PIF establishes effective embryonic-maternal communication and exerts essential trophic and protective roles by reducing oxidative stress and protein misfolding and by blunting the nocive let-7 microRNA related pathway. PIF's effects on systemic immunity lead to comprehensive immune modulation, not immune suppression. We examine PIF's role in protecting embryos from adverse maternal environment, which can lead to neurological disorders that may only manifest post-nataly: Synthetic PIF successfully translates endogenous PIF features in both pregnant and non-pregnant clinically relevant models. Specifically PIF has neuroprotective effects in neonatal prematurity. In adult relapsing-remitting neuroinflammation, PIF reverses advanced paralysis while promoting neurogenesis. PIF reversed Mycobacterium smegmatis induced brain infection. In graft-vs.-host disease, PIF reduced skin ulceration, liver inflammation and colon ulceration while maintaining beneficial anti-cancer, graft-vs.-leukemia effect. Clinical-grade PIF has high-safety profile even at supraphysiological doses. The FDA awarded Fast-Track designation, and university-sponsored clinical trials for autoimmune disorder are ongoing. Altogether, PIF properties point to its determining regulatory role in immunity, inflammation and transplant acceptance. Specific plans for using PIF for the treatment of complex neurological disorders (ie. traumatic brain injury, progressive paralysis), including neuroprotection from newborn to adult, are presented.

Impact of comorbidities on overall survival in patients with chronic myeloid leukemia: results of the randomized CML study IV.

We studied the influence of comorbidities on remission rate and overall survival (OS) in patients with chronic myeloid leukemia (CML). Participants of the CML Study IV, a randomized 5-arm trial designed to optimize imatinib therapy, were analyzed for comorbidities at diagnosis using the Charlson Comorbidity Index (CCI); 511 indexed comorbidities were reported in 1519 CML patients. Age was an additional risk factor in 863 patients. Resulting CCI scores were as follows: CCI 2, n = 589; CCI 3 or 4, n = 599; CCI 5 or 6, n = 229; and CCI ≥ 7, n = 102. No differences in cumulative incidences of accelerated phase, blast crisis, or remission rates were observed between patients in the different CCI groups. Higher CCI was significantly associated with lower OS probabilities. The 8-year OS probabilities were 93.6%, 89.4%, 77.6%, and 46.4% for patients with CCI 2, 3 to 4, 5 to 6, and ≥7, respectively. In multivariate analysis, CCI was the most powerful predictor of OS, which was still valid after removal of its age-related components. Comorbidities have no impact on treatment success but do have a negative effect on OS, indicating that survival of patients with CML is determined more by comorbidities than by CML itself. OS may therefore be inappropriate as an outcome measure for specific CML treatments. The trial was registered at www.clinicaltrials.gov as #NCT00055874.

Investigating the role of free-ranging wild boar (Sus scrofa) in the re-emergence of enzootic pneumonia in domestic pig herds: a pathological, prevalence and risk-factor study

Enzootic pneumonia (EP) caused by Mycoplasma hyopneumoniae has a significant economic impact on domestic pig production. A control program carried out from 1999 to 2003 successfully reduced disease occurrence in domestic pigs in Switzerland, but recurrent outbreaks suggested a potential role of free-ranging wild boar (Sus scrofa) as a source of re-infection. Since little is known on the epidemiology of EP in wild boar populations, our aims were: (1) to estimate the prevalence of M. hyopneumoniae infections in wild boar in Switzerland; (2) to identify risk factors for infection in wild boar; and (3) to assess whether infection in wild boar is associated with the same gross and microscopic lesions typical of EP in domestic pigs. Nasal swabs, bronchial swabs and lung samples were collected from 978 wild boar from five study areas in Switzerland between October 2011 and May 2013. Swabs were analyzed by qualitative real time PCR and a histopathological study was conducted on lung tissues. Risk factor analysis was performed using multivariable logistic regression modeling. Overall prevalence in nasal swabs was 26.2% (95% CI 23.3-29.3%) but significant geographical differences were observed. Wild boar density, occurrence of EP outbreaks in domestic pigs and young age were identified as risk factors for infection. There was a significant association between infection and lesions consistent with EP in domestic pigs. We have concluded that M. hyopneumoniae is widespread in the Swiss wild boar population, that the same risk factors for infection of domestic pigs also act as risk factors for infection of wild boar, and that infected wild boar develop lesions similar to those found in domestic pigs. However, based on our data and the outbreak pattern in domestic pigs, we propose that spillover from domestic pigs to wild boar is more likely than transmission from wild boar to pigs.

Influence and Impact of Cognitive Trajectories on Outcome in Patients Undergoing Radical Cystectomy: an Observational Study

OBJECTIVES To evaluate cognitive trajectories after radical cystectomy and their impact on surgical outcomes, including urinary continence. METHODS Ninety patients received cognitive testing using the Mini Mental State Exam (MMSE) before open radical cystectomy as well as 3 days and 2 weeks after surgery. Based on MMSE changes ≥3 points between the three time points, five cognitive trajectories emerged (stable cognition, persistent or transient deterioration or persistent or transient improvement). Surgical outcomes were assessed 90 days, 6 months and 1 year postoperatively. RESULTS Mean age was 67.9 ± 9.3 years (range 40 - 88 years). Sixty-six patients (73.3%) had stable cognition, nine patients (10.0%) persistent and seven patients (7.8%) transient deterioration, five patients (5.6%) persistent and three patients (3.3%) transient improvement. An impaired preoperative cognition was the only significant risk factor of short-term cognitive deterioration (OR adjusted for age and sex 9.4, 95%CI 1.6-56.5, p=0.014). Cognition showed no associations with 1-year mortality, 90-day complication rate, cancer progression or duration of in-hospital stay. Patients with transient or persistent cognitive deterioration had an increased risk for nighttime incontinence (OR adjusted for age and sex 5.1, 95%CI 1.1-22.4, p=0.032). CONCLUSIONS In this study, the majority of patients showed stable cognition after major abdominopelvic surgery. Cognitive deterioration occurred in a small subgroup of patients, and an impaired preoperative cognition was the only significant risk factor. Postoperative cognitive deterioration was associated with nighttime incontinence.

Impact of above- and below-ground invertebrates on temporal and spatial stability of grassland of different diversity

1. Recent theoretical studies suggest that the stability of ecosystem processes is not governed by diversity per se, but by multitrophic interactions in complex communities. However, experimental evidence supporting this assumption is scarce.2. We investigated the impact of plant diversity and the presence of above- and below-ground invertebrates on the stability of plant community productivity in space and time, as well as the interrelationship between both stability measures in experimental grassland communities.3. We sampled above-ground plant biomass on subplots with manipulated above- and below-ground invertebrate densities of a grassland biodiversity experiment (Jena Experiment) 1, 4 and 6 years after the establishment of the treatments to investigate temporal stability. Moreover, we harvested spatial replicates at the last sampling date to explore spatial stability.4. The coefficient of variation of spatial and temporal replicates served as a proxy for ecosystem stability. Both spatial and temporal stability increased to a similar extent with plant diversity. Moreover, there was a positive correlation between spatial and temporal stability, and elevated plant density might be a crucial factor governing the stability of diverse plant communities.5. Above-ground insects generally increased temporal stability, whereas impacts of both earthworms and above-ground insects depended on plant species richness and the presence of grasses. These results suggest that inconsistent results of previous studies on the diversity–stability relationship have in part been due to neglecting higher trophic-level interactions governing ecosystem stability.6. Changes in plant species diversity in one trophic level are thus unlikely to mirror changes in multitrophic interrelationships. Our results suggest that both above- and below-ground invertebrates decouple the relationship between spatial and temporal stability of plant community productivity by differently affecting the homogenizing mechanisms of plants in diverse plant communities.7.Synthesis. Species extinctions and accompanying changes in multitrophic interactions are likely to result not only in alterations in the magnitude of ecosystem functions but also in its variability complicating the assessment and prediction of consequences of current biodiversity loss.

Impact of oral diseases and disorders on oral health-related quality of life of preschool children

BACKGROUND The presence of oral diseases and disorders can produce an impact on the quality of life of preschool children and their parents, affecting their oral health and well-being. However, socioeconomic factors could confound this association, but it has not been yet tested at this age. OBJECTIVE To assess the impact of early childhood caries (ECC), traumatic dental injuries (TDI) and malocclusions on the oral health-related quality of life (OHRQoL) of children between 2 and 5 years of age adjusted by socioeconomic factors. METHODS Parents of 260 children answered the Early Childhood Oral Health Impact Scale (ECOHIS) (six domains) on their perception of the children's OHRQoL and socioeconomic conditions. Two calibrated dentists (κ>0.8) examined the severity of ECC according to dmft index, and children were categorized into: 0=caries free; 1-5=low severity; ≥6=high severity. TDI and malocclusions were examined according to Andreasen & Andreasen (1994) classification and for the presence or absence of three anterior malocclusion traits (AMT), respectively. OHRQoL was measured through ECOHIS domain and total scores, and poisson regression was used to associate the different factors with the outcome. RESULTS In each domain and overall ECOHIS scores, the severity of ECC showed a negative impact on OHRQoL (P<0.001). TDI and AMT did not show a negative impact on OHRQoL nor in each domain (P>0.05). The increase in the child's age, higher household crowding, lower family income and mother working out of home were significantly associated with OHRQoL (P<0.05). The multivariate adjusted model showed that the high severity of ECC (RR=3.81; 95% CI=2.66, 5.46; P<0.001) was associated with greater negative impact on OHRQoL, while high family income was a protective factor for OHRQoL (RR=0.93; 95% CI=0.87, 0.99; P<0.001). CONCLUSIONS The severity of ECC and a lower family income had a negative impact on the OHRQoL of preschool children and their parents.