The impact of nocturnal road traffic noise, bedroom window orientation, and work-related stress on subjective sleep quality: results of a cross-sectional study among working women.

OBJECTIVE: To examine the effect of work-related stress and road noise exposure on self-rated sleep and potential additive interaction effects. METHODS: Sleep and predictor variables were surveyed within two subsamples with 2191 and 1764 working women in a cross-sectional study. Sleep was assessed using a single question on general sleep quality and four questions on specific sleep problems and subsequently dichotomized (poor sleep vs. no poor sleep). Work-related stress was operationalized by job strain and effort-reward imbalance. Nocturnal exposure to road traffic noise was assessed as (a) the orientation of the bedroom window to a quiet façade vs. a low-, medium- or high-trafficked street and (b) energy-equivalent sound pressure levels for night-time modelled at the most exposed façade (Lnight). We distinguished between low (< 45 dB(A)), medium (45-50 dB(A)) and high exposure (> 50 dB(A)). RESULTS: Poor sleep was associated with job strain and effort-reward imbalance. The prevalence of poor sleep did not increase with increasing Lnight, but bedroom window orientation showed a non-significant trend. A quiet façade had a protective effect on sleep in each Lnight category. We found a non-significant trend for an additive interaction between bedroom window orientation and job strain. CONCLUSION: Noise levels modelled for the most exposed façade likely overestimate the actual exposure and thus may not be a precise predictor of poor sleep. Bedroom window orientation seems more relevant. Potential additive interaction effects between bedroom window orientation and job strain should be considered when interpreting epidemiological study results on noise-induced sleep disturbances.

Electroencephalographic findings in schizophreniform and affective disorders.

OBJECTIVE: Pathological findings in electroencephalography (EEG) are discussed as a possible marker of organic mental disorders and a therapeutic response to anticonvulsive medication under these conditions. METHODS: We compared the prevalence of EEG abnormalities in 100 patients with schizophrenia, 100 patients with schizoaffective disorder, 51 patients with acute polymorphic psychotic disorder, 100 patients with bipolar disorder, 100 patients with unipolar major depression and 76 healthy control subjects with the findings of a previous study using well-diagnosed, large control samples (13,658 pilots and aircrew personnel). RESULTS: We detected an increased number of pathological EEG findings with intermittent rhythmic delta or theta activity in 7% of patients with schizophrenia, 7% of patients with schizoaffective disorder, 5.9% of patients with acute polymorphic psychosis, 6% of patients with bipolar disorder, 4% of unipolar depressed patients and 3.9% of the own control group, compared to 1% of strictly controlled healthy subjects. One-sided logistic regression revealed an association between pathological EEGs and the diagnosis of schizophrenia (Wald W = 3.466, p = 0.0315), schizoaffective disorder (W = 3.466, p = 0.0315) and bipolar disorder (W = 2.862, p = 0.0455). CONCLUSIONS: We suggest that the previously developed local area network inhibition model for a potential paraepileptic pathomechanism can explain the relevance of such findings in different psychiatric disorders.

Brain tumors in children with refractory seizures­a long-term follow-up study after epilepsy surgery.

PURPOSE: Epilepsy surgery is an established treatment option for medically refractory epilepsy. Brain tumors, besides dysplasias, vascular malformations, and other lesions, can cause refractory epilepsy. Long-term epilepsy-associated brain tumors, even though mostly benign, are neoplastic lesions and thus have to be considered as both epileptic and oncological lesions. METHODS: We retrospectively analyzed epileptological and oncological long-term follow-up (FU) in pediatric patients who underwent brain surgery for refractory epilepsy and whose histology showed a tumor as underlying cause (n = 107, mean FU 119 months). RESULTS: At last available outcome, 82.2% of patients were seizure free (International League Against Epilepsy (ILAE) class 1) and seizure outcome was stable over more than 14 years. Fifty-four percent of the patients were without anti-epileptic drugs (AEDs) at last available outcome; 96.2% of the tumors were classified WHO grade I and II and 3.7% were malignant (WHO grade III). Adjuvant treatment was administered in 5.7%; 2.9% had relapse and one patient died (tumor-related mortality = 1.4%). After surgery, 91% of the patients attended regular school/university and/or professional training. CONCLUSIONS: This study shows that epileptological outcome within this group is promising and stable and oncological outcome has a very good prognosis. However, oncological FU must not be dismissed as a small percentage of patients who suffer from malignant tumors and adjuvant treatment, relapse, and mortality have to be considered.

Traditional risk factors are not major contributors to the variance in carotid intima-media thickness.

BACKGROUND AND PURPOSE: Carotid intima-media thickness (cIMT) was a widely accepted ultrasound marker of subclinical atherosclerosis in the past. Although traditional risk factors may explain ≈50% of the variance in plaque burden, they may not explain such a high proportion of the variance in IMT, especially when measured in plaque-freel ocations. We aimed this study to identify individuals with cIMT unexplained by traditional risk factors for future environmental and genetic research. METHODS: As part of the Northern Manhattan Study, 1790 stroke-free individuals (mean age, 69±9 years; 60% women; 61% Hispanic; 19% black; 18% white) were assessed for cIMT using B-mode carotid ultrasound. Multiple linear regression models were evaluated: (1) incorporating prespecified traditional risk factors; and (2) including less traditional factors, such as inflammation biomarkers, adiponectin, homocysteine, and kidney function. Standardized cIMT residual scores were constructed to select individuals with unexplained cIMT. RESULTS: Mean total cIMT was 0.92±0.09 mm. The traditional model explained 11% of the variance in cIMT. Age (7%), male sex (3%), glucose (<1%), pack-years of smoking (<1%), and low-density lipoprotein cholesterol (<1%) were significant contributing factors. The model, including inflammatory biomarkers, explained 16% of the variance in cIMT. Adiponectin was the only additional significant contributor to the variance in cIMT. We identified 358 individuals (20%) with cIMT unexplained by the investigated risk factors. CONCLUSIONS: Vascular risk factors explain only a small proportion of variance in cIMT. Identification of novel genetic and environmental factors underlying unexplained subclinical atherosclerosis is of utmost importance for future effective prevention of vascular disease.

Being a Fair Neighbor-Towards a Psychometric Inventory to Assess Fairness-Related Perceptions of Airports by Residents-Development and Validation of the Aircraft Noise-Related Fairness Inventory (fAIR-In).

Aircraft noise causes a variety of negative health consequences, and annoyance is a central factor mediating stress-related health risks. Non-acoustic factors play an important role in the experience of annoyance where the aspect of fairness is assumed to be a vital component. This paper describes the development of the Aircraft Noise-related Fairness Inventory (fAIR-In) and examines its factorial validity, construct validity and predictive validity. The development of the questionnaire included expert consultations, statements from airport residents and a large-scale online survey around three German airports (N = 1367). Its items cover distributive, procedural, informational and interpersonal fairness. Via mailshot, almost 100,000 flyers were sent out in more (>55 dB(A) Lden)- and less (≤55 dB(A) Lden)-aircraft-noise-exposed areas around Cologne-Bonn, Dusseldorf and Dortmund Airport. Thirty-two items were carefully selected considering reliability, theoretical importance and factor loading calculated via exploratory factor analysis (EFA), with all facets achieving high internal consistency (α = 0.89 to 0.92). The factorial validity, analyzed via a confirmatory factor analysis (CFA), revealed that viewing distributive, procedural, informational and interpersonal fairness as distinct factors produced a better fit to the data than other categorizations with fewer factors. The fAIR-In shows adequate results in terms of construct validity and excellent results in terms of the predictive validity of annoyance by aircraft noise (r = -0.53 to r = -0.68), acceptance of airports and air traffic (r = 0.46 to r = 0.59) and willingness to protest (r = -0.28 to r = -0.46). The fAIR-In provides airport managers with a reliable, valid and easy-to-use tool to design, monitor and evaluate efforts to improve the neighborliness between an airport and its residents.

Hematopoietic stem cell transplantation without irradiation.

Hematopoietic stem cell (HSC) transplantation is limited by histocompatibility barriers and by lack of space in bone marrow niches. These obstacles prevent in vivo analysis of histoincompatible mutant stem cells and of HSC functions in non-irradiated mice. By genetically combining immunodeficiency with impaired function of the growth factor receptor Kit in mice, we generated a 'universal' HSC recipient that efficiently accepts long-term histocompatible and histoincompatible HSCs without prior irradiation.

Aircraft Noise Distribution as a Fairness Dilemma-A Review of Aircraft Noise through the Lens of Social Justice Research.

Aircraft noise exposure is a health risk and there is evidence that noise annoyance partly mediates the association between noise exposure and stress-related health risks. Thus, approaches to reduce annoyance may be beneficial for health. Annoyance is influenced by manifold non-acoustic factors and perceiving a fair and trustful relationship between the airport and its residents may be one of them. The distribution of aircraft noise exposure can be regarded as a fairness dilemma: while residents living near an airport may seem to have some advantages, the majority of residents living under certain flight routes or in their immediate proximity suffer from the disadvantages of the airport, especially the noise. Moreover, a dilemma exists between the airport's beneficial economic impact for a region and the physical and psychological integrity of residents. Aircraft noise exposure through the lens of social justice research can help to improve our understanding of noise annoyance. Research indicates that the fairness perceptions of the parties involved can be enhanced by (a) improving individual cost-benefit ratios, (b) providing a fair procedure for deciding upon the noise distribution, and (c) implementing fair social interaction with residents. Based on the review of evidence from social justice research, we derive recommendations on how fairness aspects can be integrated into aircraft noise management with the purpose of improving the relationship between the airport and its residents, to reduce annoyance, and to enhance the acceptance of local aviation and the airport as a neighbor.

Effects of Nocturnal Aircraft Noise and Non-Acoustical Factors on Short-Term Annoyance in Primary School Children.

Children are considered at higher risk for harmful noise effects due to their sensitive development phase. Here, we investigated the effects of nocturnal aircraft noise exposure on short-term annoyance assessed in the morning in 51 primary school children (8-10 years) living in the surrounding community of Cologne-Bonn Airport. Child-appropriate short-term annoyance assessments and associated non-acoustical variables were surveyed. Nocturnal aircraft noise exposure was recorded inside the children's bedrooms. Exposure-response models were calculated by using random effects logistic regression models. The present data were compared with those from a previous study near Cologne-Bonn Airport in adults using very similar methodology. Short-term annoyance reaction in children was not affected by the nocturnal aircraft noise exposure. Non-acoustical factors (e.g., the attitude that "aircraft are dangerous" or noise sensitivity), however, significantly impacted on children's short-term annoyance. In contrast to children, the probability of moderate to high annoyance in adults increased with the number of aircraft flyovers during the time in bed. It is concluded that short-term annoyance from nocturnal aircraft noise in children is mainly determined by non-acoustical factors. Unlike in adults, acoustical factors did not play a significant role.

Influence of transient pressure changes on speech intelligibility: Implications for next-generation train travel.

High-speed trains are operated in increasingly complex railway networks and continual improvement of driver assistance systems is necessary to maintain safety. Speech offers the opportunity to provide information to the driver without disrupting visual attention. However, it is not known whether the transient pressure changes inside trains passing through tunnels interfere with speech intelligibility. Our primary goal was to test whether the most severe pressure variations occurring in high-speed trains (25 hPa in 2 s) affect speech intelligibility in individuals with normal hearing ability and secondly whether a potential effect would depend on the direction of the pressure change. A cross-over design was used to compare speech intelligibility, measured with the monosyllable word test by Wallenberg and Kollmeier, in steady ambient pressure versus subsequent to pressure events, both realised in a pressure chamber. Since data for a power calculation did not exist, we conducted a pilot study with 20 participants to estimate variance of intra-individual differences. The upper 80% confidence limit guided sample size of the main campaign, which was performed with 72 participants to identify a 10% difference while limiting alpha (5%) and beta error (10%). On average, a participant understood 0.7 fewer words following a pressure change event compared to listening in steady ambient pressure. However, this intra-individual differences varied strongly between participants, standard deviation (SD) ± 4.5 words, resulting in a negligible effect size of 0.1 and the Wilcoxon signed rank test (Z = -1.26; p = 0.21) did not distinguish it from chance. When comparing decreasing and increasing pressure events an average of 0.2 fewer words were understood (± 3.9 SD). The most severe pressure changes expected to occur in high-speed trains passing through tunnels do not interfere with speech intelligibility and are in itself not a risk factor for loss of verbal information transmission.

Endothelial cell fitness dictates the source of regenerating liver vasculature.

Neoangiogenesis plays a key role in diverse pathophysiological conditions, including liver regeneration. Yet, the source of new endothelial cells (ECs) remains elusive. By analyzing the regeneration of the liver vasculature in irradiation-based myeloablative and nonmyeloablative bone marrow transplantation mouse models, we discovered that neoangiogenesis in livers with intact endothelium was solely mediated by proliferation of resident ECs. However, following irradiation-induced EC damage, bone marrow-derived mononuclear cells were recruited and incorporated into the vasculature. Further experiments with direct bone marrow infusion or granulocyte colony-stimulating factor (G-CSF)-mediated progenitor cell mobilization, which resembles clinically relevant stem cell therapy, demonstrated that bone marrow-derived cells did not contribute to the regeneration of liver vasculature after two-thirds partial hepatectomy (PHx). Taken together, the data reconcile many of the discrepancies in the literature and highlight that the cellular source of regenerating endothelium depends on the fitness of the residual vasculature.

Increased Prevalence of Intermittent Rhythmic Delta or Theta Activity (IRDA/IRTA) in the Electroencephalograms (EEGs) of Patients with Borderline Personality Disorder.

INTRODUCTION: An increased prevalence of pathological electroencephalography (EEG) signals has been reported in patients with borderline personality disorder (BPD). In an elaborative case description of such a patient with intermittent rhythmic delta and theta activity (IRDA/IRTA), the BPD symptoms where linked to the frequency of the IRDAs/IRTAs and vanished with the IRDAs/IRTAs following anticonvulsive therapy. This observation raised a question regarding the prevalence of such EEG abnormalities in BPD patients. The aim of this retrospective study was to identify the frequency of EEG abnormalities in a carefully analyzed psychiatric collective. Following earlier reports, we hypothesized an increased prevalence of EEG abnormalities in BPD patients. PARTICIPANTS AND METHODS: We recruited 96 consecutive patients with BPD from the archive of a university clinic for psychiatry and psychotherapy, and compared the prevalence of EEG abnormalities to those of 76 healthy controls subjects. The EEGs were rated by three different blinded clinicians, including a consultant specializing in epilepsy from the local epilepsy center. RESULTS: We found a significant increase in the prevalence of IRDAs and IRTAs in BPD patients (14.6%) compared to the control subjects (3.9%; p = 0.020). DISCUSSION: In this blinded retrospective case-control study, we were able to confirm an increased prevalence of pathological EEG findings (IRDAs/IRTAs only) in BPD patients. The major limitation of this study is that the control group was not matched on age and gender. Therefore, the results should be regarded as preliminary findings of an open uncontrolled, retrospective study. Future research performing prospective, controlled studies is needed to verify our findings and answer the question of whether such EEG findings might predict a positive response to anticonvulsive pharmacological treatment.

The influence of acoustical and non-acoustical factors on short-term annoyance due to aircraft noise in the field - The COSMA study.

BACKGROUND: Air traffic has increased for the past decades and is forecasted to continue to grow. Noise due to current airport operations can impair the physical and psychological well-being of airport residents. OBJECTIVES: The field study investigated aircraft noise-induced short-term (i.e., within hourly intervals) annoyance in local residents near a busy airport. We aimed at examining the contribution of acoustical and non-acoustical factors to the annoyance rating. METHODS: Across four days from getting up till going to bed, 55 residents near Cologne/Bonn Airport (M=46years, SD=14years, 34 female) rated their annoyance due to aircraft noise at hourly intervals. For each participant and each hour, 26 noise metrics from outdoor measurements and further 6 individualized metrics that took into account the sound attenuation due to each person's whereabouts in and around their homes were obtained. Non-acoustical variables were differentiated into situational factors (time of day, performed activity during past hour, day of the week) and personal factors (e.g., sensitivity to noise, attitudes, domestic noise insulation). Generalized Estimation Equations were applied for the development of a prediction model for annoyance. RESULTS: Acoustical factors explained only a small proportion (13.7%) of the variance in the annoyance ratings. The number of fly-overs predicted annoyance better than did equivalent and maximum sound pressure levels. The proportion of explained variance in annoyance rose considerably (to 27.6%) when individualized noise metrics as well as situational and personal variables were included in the prediction model. CONCLUSIONS: Consideration of noise metrics related to the number of fly-overs and individual adjustment of noise metrics can improve the prediction of short-term annoyance compared to models using equivalent outdoor levels only. Non-acoustical factors have remarkable impact not only on long-term annoyance as shown before but also on short-term annoyance judged in the home environment.

Possible morphological pathomechanisms of ischemic stroke in the posterior circulation of patients with vertebral artery hypoplasia.

BACKGROUND: The clinical significance of vertebral artery hypoplasia (VAH) and the possible pathomechanism of ischemic stroke in patients with VAH are still not completely clear. METHODS: In a group of 80 posterior circulation strokes (PCS) patients, we compared the location of the ischemic areas in VAH (n = 26) and non-VAH (n = 54) group. We assessed the side of VAH (diameter equal to or less than 2.5 mm) with the stroke localization. RESULTS: The possible morphological stroke pathomechanisms in the VAH group--"blood flow reorganization" (n = 11) and "pathway liberation for embolization" (n = 10) - were represented equally and may also act together (n = 3). In two cases, the stroke pathomechanism was unknown. The frequency of the presence of conventional risk factors--hypertension (p = 1.0), diabetes mellitus (p = 0.62), hyperlipidemia (p= 1.0) and smoking (p = 1.0)--and the stroke etiology--cardioembolism (p = 0.80), atherosclerotic changes of large (p = 0.76) and small vessels (p = 0.79)--did not differ between the two subgroups. CONCLUSION: In patients with VAH, the combination of several pathomechanisms of ischemic stroke and the contribution of several risk factors can cause the clinical manifestation of PCS.

Endothelial cell-derived angiopoietin-2 controls liver regeneration as a spatiotemporal rheostat.

Liver regeneration requires spatially and temporally precisely coordinated proliferation of the two major hepatic cell populations, hepatocytes and liver sinusoidal endothelial cells (LSECs), to reconstitute liver structure and function. The underlying mechanisms of this complex molecular cross-talk remain elusive. Here, we show that the expression of Angiopoietin-2 (Ang2) in LSECs is dynamically regulated after partial hepatectomy. During the early inductive phase of liver regeneration, Ang2 down-regulation leads to reduced LSEC transforming growth factor-ß1 production, enabling hepatocyte proliferation by releasing an angiocrine proliferative brake. During the later angiogenic phase of liver regeneration, recovery of endothelial Ang2 expression enables regenerative angiogenesis by controlling LSEC vascular endothelial growth factor receptor 2 expression. The data establish LSECs as a dynamic rheostat of liver regeneration, spatiotemporally orchestrating hepatocyte and LSEC proliferation through angiocrine- and autocrine-acting Ang2, respectively.

Angiopoietin-2 differentially regulates angiogenesis through TIE2 and integrin signaling.

Angiopoietin-2 (ANG-2) is a key regulator of angiogenesis that exerts context-dependent effects on ECs. ANG-2 binds the endothelial-specific receptor tyrosine kinase 2 (TIE2) and acts as a negative regulator of ANG-1/TIE2 signaling during angiogenesis, thereby controlling the responsiveness of ECs to exogenous cytokines. Recent data from tumors indicate that under certain conditions ANG-2 can also promote angiogenesis. However, the molecular mechanisms of dual ANG-2 functions are poorly understood. Here, we identify a model for the opposing roles of ANG-2 in angiogenesis. We found that angiogenesis-activated endothelium harbored a subpopulation of TIE2-negative ECs (TIE2lo). TIE2 expression was downregulated in angiogenic ECs, which abundantly expressed several integrins. ANG-2 bound to these integrins in TIE2lo ECs, subsequently inducing, in a TIE2-independent manner, phosphorylation of the integrin adaptor protein FAK, resulting in RAC1 activation, migration, and sprouting angiogenesis. Correspondingly, in vivo ANG-2 blockade interfered with integrin signaling and inhibited FAK phosphorylation and sprouting angiogenesis of TIE2lo ECs. These data establish a contextual model whereby differential TIE2 and integrin expression, binding, and activation control the role of ANG-2 in angiogenesis. The results of this study have immediate translational implications for the therapeutic exploitation of angiopoietin signaling.

Kit is essential for PMA-inflammation-induced mast-cell accumulation in the skin.

Cutaneous mast cells have important pathogenic roles in skin inflammation, but the signals regulating mast-cell numbers in healthy and inflamed skin are not fully understood. Mast-cell development depends on the receptor tyrosine kinase Kit as shown by a greater than 95% reduction of mast-cell numbers in hypomorphic (Kit(W/Wv)) mutant mice that are widely used as a mast-cell deficiency model. Mast-cell numbers are normally very low in Kit(W/Wv) mice, but numbers can strongly increase under inflammatory conditions. It remains elusive whether this inflammation-driven mast-cell accumulation is mediated by signals transmitted via the Kit(Wv) receptor or by other, Kit-independent stimuli. We show here, using viable Kit- null mice (Kit(W/W)), that Kit is essential for mast-cell accumulation in phorbol-12-myristate-13-acetate (PMA)-treated, chronically inflamed skin. This increase in mast- cell numbers is strongly attenuated in Kit(W/Wv) mice lacking mature lymphocytes (T, B, and natural killer [NK] cells). These data, together with reconstitution experiments, point at a role for lymphocytes in the regulation of mast-cell compartments under limiting Kit signaling. We conclude that inflammation-induced cutaneous mast-cell accumulation is dependent on Kit signaling strength, and, under limiting Kit signals, on cells of the adaptive immune system.