The Global Atmosphere-aerosol Model ICON-A-HAM2.3-Initial Model Evaluation and Effects of Radiation Balance Tuning on Aerosol Optical Thickness.

The Hamburg Aerosol Module version 2.3 (HAM2.3) from the ECHAM6.3-HAM2.3 global atmosphere-aerosol model is coupled to the recently developed icosahedral nonhydrostatic ICON-A (icon-aes-1.3.00) global atmosphere model to yield the new ICON-A-HAM2.3 atmosphere-aerosol model. The ICON-A and ECHAM6.3 host models use different dynamical cores, parameterizations of vertical mixing due to sub-grid scale turbulence, and parameter settings for radiation balance tuning. Here, we study the role of the different host models for simulated aerosol optical thickness (AOT) and evaluate impacts of using HAM2.3 and the ECHAM6-HAM2.3 two-moment cloud microphysics scheme on several meteorological variables. Sensitivity runs show that a positive AOT bias over the subtropical oceans is remedied in ICON-A-HAM2.3 because of a different default setting of a parameter in the moist convection parameterization of the host models. The global mean AOT is biased low compared to MODIS satellite instrument retrievals in ICON-A-HAM2.3 and ECHAM6.3-HAM2.3, but the bias is larger in ICON-A-HAM2.3 because negative AOT biases over the Amazon, the African rain forest, and the northern Indian Ocean are no longer compensated by high biases over the sub-tropical oceans. ICON-A-HAM2.3 shows a moderate improvement with respect to AOT observations at AERONET sites. A multivariable bias score combining biases of several meteorological variables into a single number is larger in ICON-A-HAM2.3 compared to standard ICON-A and standard ECHAM6.3. In the tropics, this multivariable bias is of similar magnitude in ICON-A-HAM2.3 and in ECHAM6.3-HAM2.3. In the extra-tropics, a smaller multivariable bias is found for ICON-A-HAM2.3 than for ECHAM6.3-HAM2.3.

Patient individual phase gating for stereotactic radiation therapy of early stage non-small cell lung cancer (NSCLC).

Stereotactic body radiotherapy (SBRT) applies high doses and requires advanced techniques to spare surrounding tissue in the presence of organ motion. In this work patient individual phase gating is investigated. We studied peripheral and central primary lung tumors. The internal target volume (ITV) was defined including different numbers of phases picked from a 4D Computed tomography (CT) defining the gating window (gw). Planning target volume (PTV) reductions depending on the gw were analyzed. A treatment plan was calculated on a reference phase CT (rCT) and the dose for each breathing phase was calculated and accumulated on the rCT. We compared the dosimetric results with the dose calculated when all breathing phases were included for ITV definition. GWs including 1 to 10 breathing phases were analyzed. We found PTV reductions up to 38.4%. The mean reduction of the lung volume receiving 20 Gy due to gating was found to be 25.7% for peripheral tumors and 16.7% for central tumors. Gating considerably reduced esophageal doses. However, we found that simple reduction of the gw does not necessarily influence the dose in a clinically relevant range. Thus, we suggest a patient individual definition of the breathing phases included within the gw.

Recent declines in salmon body size impact ecosystems and fisheries.

Declines in animal body sizes are widely reported and likely impact ecological interactions and ecosystem services. For harvested species subject to multiple stressors, limited understanding of the causes and consequences of size declines impedes prediction, prevention, and mitigation. We highlight widespread declines in Pacific salmon size based on 60 years of measurements from 12.5 million fish across Alaska, the last largely pristine North American salmon-producing region. Declines in salmon size, primarily resulting from shifting age structure, are associated with climate and competition at sea. Compared to salmon maturing before 1990, the reduced size of adult salmon after 2010 has potentially resulted in substantial losses to ecosystems and people; for Chinook salmon we estimated average per-fish reductions in egg production (-16%), nutrient transport (-28%), fisheries value (-21%), and meals for rural people (-26%). Downsizing of organisms is a global concern, and current trends may pose substantial risks for nature and people.

Prevalence of abomasal lesions in Danish Holstein cows at the time of slaughter.

Abomasal lesions in cattle are challenging to diagnose because the clinical signs are often subtle and nonspecific. An increasing number of studies suggests that abomasal lesions are commonly found in cattle of all ages, but the number of recent prevalence studies in dairy cows is limited. The main objective of this study was to estimate the prevalence of abomasal lesions in a population of Danish Holstein dairy cattle in Denmark. An abattoir survey of 1,327 dairy cows apparently suitable for slaughter was performed in 2016 and 2017. Abomasal lesions are usually classified using a standardized protocol with the following types: abomasal ulcer type I: erosions and nonperforating ulcers; type II: ulcers with arterial bleeding; type III: perforating ulcer with localized peritonitis; and type IV: perforating ulcer with diffuse peritonitis. A further subdivision of the nonperforating abomasal ulcers type I were classified as subtype Ia: erosions; subtype Ib: small ulcers with localized hemorrhage; subtype Ic: ulcers with a crater-like appearance; and subtype Id: retention of the mucosa due to tissue loss with either radial wrinkles converging at a central point or perforations of the spiral folds. Type I abomasal lesions were found in 84% of the examined cows. No ulcers with arterial bleeding (type II) or perforating ulcers with diffuse peritonitis (type IV) were found, but one perforating abomasal ulcer (type III) was observed. The total number of lesions found was 7,418 and when the lesion subtypes were evaluated individually the majority of subtypes Ia and Ic were found in the pyloric area (85 and 94%, respectively), whereas lesion subtypes Ib and Id dominated the fundus/corpus area (71 and 67%, respectively). When considering lesion subtypes according to parity, there was a high prevalence of subtype Ib across the 3 groups of parity (51, 58, and 55% for parity 1, 2, and ≥3, respectively). The prevalence of lesion subtype Id seemed to increase with increasing parity, and the prevalence of lesion subtype Ia seemed to decrease with increasing parity. The prevalence of abomasal lesions was higher than that shown in similar studies of cattle at the time of slaughter. However, the expectedly most painful cases were rare, with only one perforating and no arterial bleeding ulcers found. The etiology of the different subtype I lesions is still unknown, and further investigations are needed to establish the possible influence these lesions might have on welfare and production.

Prognostic factors in stereotactic body radiotherapy of lung metastases.

PURPOSE: The aim of this study was to evaluate prognostic factors in patients with lung metastases who undergo lung stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: A total of 87 patients with 129 lung metastases who underwent SBRT between November 2004 and May 2012 were enrolled in this retrospective study. The patient collective consisted of 54 men (62.1%) and 33 women (37.9%); the median age was 65 years (range 36-88). The Karnofsky performance index was ≥70% (median 90%) for all cases, but one (60%). Adverse effects were categorized using the CTCAE 4.0 classification system. Retrospective analyses regarding patients' characteristics, progression-free survival (PFS), overall survival (OS), disease-specific survival (DSS), and local tumor control rates (LTC) were performed. RESULTS: On univariate and multivariate analysis OS, DSS, and PFS were significantly (p < 0.05) better for patients with ≤3 lung metastases; no extrathoracic metastases at the time of the SBRT; a gross tumor volume (GTV) <7.7 cm3 and patients that received a staging that included positron emission tomography with fluorine 18 fluorodeoxyglucose/computed tomography (FDG-PET/CT) imaging. Furthermore, a longer OS was observed if newly diagnosed metastases during follow-up were limited to the lung (median survival: 43.7 months versus 21.7 months; p = 0.023). CONCLUSION: The number and pattern of metastases, and the size of the target volume are strong predictors for the outcome of patients receiving SBRT of lung tumors. FDG-PET/CT should be part of pretherapeutic staging before SBRT.

DVH- and NTCP-based dosimetric comparison of different longitudinal margins for VMAT-IMRT of esophageal cancer.

PURPOSE: To cover the microscopic tumor spread in squamous cell carcinoma of the esophagus (SCC), longitudinal margins of 3-4 cm are used for radiotherapy (RT) protocols. However, smaller margins of 2-3 cm might be reasonable when advanced diagnostic imaging is integrated into target volume delineation. Purpose of this study was to compare the dose distribution and deposition to the organs at risk (OAR) for different longitudinal margins using a DVH- and NTCP-based approach. METHODS: Ten patients with SCC of the middle or lower third were retrospectively selected. Three planning target volumes (PTV) with longitudinal margins of 4 cm, 3 cm and 2 cm and an axial margin of 1.5 cm to the gross target volume (GTV) were defined for each patient. For each PTV two treatment plans with total doses of 41.4 Gy (neoadjuvant treatment) and 50.4 Gy (definite treatment) were calculated. Dose to the lungs, heart, myelon and liver were then evaluated and compared between different PTVs. RESULTS: When using a longitudinal margin of 3 cm instead of 4 cm, all dose parameters (Dmin, Dmean, Dmedian and V5-V35), except Dmax could be significantly reduced for the lungs. Regarding the heart, a significant reduction was seen for Dmean and V5, but not for Dmin, Dmax, Dmedian and V10-V35. When comparing a longitudinal margin of 4 cm to a longitudinal margin of 2 cm, a significant difference was calculated for Dmin, Dmean, Dmedian and V5-V35 of the lungs and for Dmax, Dmean and V5-V35 of the heart. Nevertheless, no difference was seen for median heart dose. An additional dose reduction for V10 of the heart was achieved for definite treatment plans when using a longitudinal margin of 3 cm. The NTCP-based risk of pneumonitis was significantly reduced by a margin reduction to 2 cm for neoadjuvant and definite treatment plans. CONCLUSION: Reduction of longitudinal margins from 4 cm to 3 cm can significantly reduce the dose to lungs and Dmean of the heart. Despite clinical benefit and oncologic outcome remain unclear, reduction of the longitudinal margins might provide the opportunity to reduce side effects of chemoradiation (CRT) for SCC in upcoming studies.

Dermal and transdermal delivery of pharmaceutically relevant macromolecules.

The skin offers an attractive way for dermal and transdermal drug delivery that is why the drug still needs certain qualities to transcend the outermost layer of the skin, the stratum corneum. The requirements are: drugs with a maximum molecular weight of 1kDa, high lipophilicity and a certain polarity. This would restrict the use of a transdermal delivery of macromolecules, which would make the drug more effective in therapeutic administration. Various studies have shown that macromolecules without support do not penetrate the human skin. This effect can be achieved using physical and chemical methods, as well as biological peptides. The most popular physical method is the use of microneedles to create micropores in the skin and release the active agent in different sections. But also, other methods have been tested. Microjets, lasers, electroporation, sonophoresis and iontophoresis are also promising methods to successfully deliver dermal and transdermal macromolecules. Additionally, there are different penetration enhancer groups and biological peptides, which are also considered to be interesting approaches of enabling macromolecules to travel along the skin. All these methods will be described and evaluated in this review article.

New particle formation in the free troposphere: A question of chemistry and timing.

New particle formation (NPF) is the source of over half of the atmosphere's cloud condensation nuclei, thus influencing cloud properties and Earth's energy balance. Unlike in the planetary boundary layer, few observations of NPF in the free troposphere exist. We provide observational evidence that at high altitudes, NPF occurs mainly through condensation of highly oxygenated molecules (HOMs), in addition to taking place through sulfuric acid-ammonia nucleation. Neutral nucleation is more than 10 times faster than ion-induced nucleation, and growth rates are size-dependent. NPF is restricted to a time window of 1 to 2 days after contact of the air masses with the planetary boundary layer; this is related to the time needed for oxidation of organic compounds to form HOMs. These findings require improved NPF parameterization in atmospheric models.

Evidence for the transmission of Salmonella from reptiles to children in Germany, July 2010 to October 2011.

This study examines the Salmonella status in reptiles kept in households with children suffering from gastroenteritis due to an exotic Salmonella serovar, to obtain information on possible transmission paths. A number of affected households (n=79) were contacted, and almost half (34/79) comprised at least one reptile in the home. Of the households, 19 were further studied, whereby a total of 36 reptiles were investigated. Samples were taken from the reptiles including the oral cavity, the cloaca, the skin and, in the case of lizards, the stomach, and isolation of Salmonella strains was performed using repeated enrichment and typing. Where the Salmonella serovars of the infected child and the reptile were identical, typing was followed by pulsed-field gel electrophoresis (PFGE). Bearded dragons (Pogona vitticeps) constituted 19 of 36 examined reptiles. Altogether 319 Salmonella isolates were investigated and 24 different serovars identified in the reptiles. In 15 of 19 households, an identical serovar to the human case was confirmed in at least one reptile (including 16 of all 19 bearded dragons examined). The results demonstrate that reptiles and especially bearded dragons shed various Salmonella serovars including those isolated from infected children in the respective households. Hygiene protocols and parents' education are therefore highly necessary to reduce the risk of transmission. From a terminological point of view, we propose to call such infections 'Reptile-Exotic-Pet-Associated-Salmonellosis' (REPAS).

Calcium-binding protein expression in peritoneal endometriosis-associated nerve fibres.

BACKGROUND: Recent studies demonstrated the potential involvement of nerve fibres in the chronic inflammatory process of endometriosis. We aimed to characterize nerve fibres in the proximal and distal areas of the peritoneal endometriotic lesions in order to understand the chronic inflammatory process in endometriosis. METHODS: Peritoneal endometriotic lesions (proximal area) (n = 17), the matching unaffected peritoneum (distal area) and healthy peritoneum of patients without endometriosis (n = 15) were analysed with the neuronal markers PGP 9.5, calbindin, calretinin and parvalbumin. Peritoneal fluids of women with and without endometriosis were used for Western blot analysis and for the neuronal growth assay. The protein expression of neuronal PC-12 cells incubated with peritoneal fluids was analysed. RESULTS: The overall nerve fibre density was significantly reduced in the distal area of the lesion when compared with the proximal area or with healthy peritoneum. The density of calbindin-, calretinin- and parvalbumin-positive nerve fibres was significantly increased in the endometriosis group. Calretinin expression was elevated in the peritoneal fluid of women with symptomatic endometriosis when compared with women with asymptomatic endometriosis. Furthermore, PC-12 cells incubated with peritoneal fluid of women with endometriosis showed a higher proliferation rate and a stronger neurite outgrowth than the control group. PC-12 cells incubated in peritoneal fluids of women with endometriosis expressed less calretinin but more calbindin than the control group. CONCLUSIONS: Calcium-binding proteins seem to be increased in endometriosis-associated nerve fibres and might play an important role in the chronic inflammatory condition and the pain pathogenesis of endometriosis.

Health-related quality of life in women with nausea and vomiting of pregnancy: the importance of psychosocial context.

OBJECTIVE: To test whether women with hyperemesis gravidarum (HG) demonstrated lower health-related quality of life (HRQoL) scores compared with those with nausea and vomiting of pregnancy (NVP). STUDY DESIGN: Women with HG or NVP were examined during the first trimester. Multivariate models identified characteristics of women at risk for low HRQoL, as measured by an NVP-specific HRQoL test and a generic HRQoL test, the Short Form (SF)-36. RESULT: Although the SF-36 assessment did not discriminate between the two groups, the NVP-specific test showed that women with HG (N=29) were 3-6 times more likely than women with NVP (N=48) to have low HRQoL. Both tests demonstrated that perceived physical symptoms and multiple psychosocial factors, such as depression and marital status, seemed to be equally or more important than having HG. CONCLUSION: Although a low HRQoL was associated with an HG diagnosis, multiple physical symptoms and psychosocial factors placed both groups of women at risk.

Time-resolved photoluminescence investigations on HfO2-capped InP nanowires.

We have employed time-resolved photoluminescence (PL) spectroscopy to study the impact of HfO(2) surface capping by atomic layer deposition (ALD) on the optical properties of InP nanowires (NWs). The deposition of high-kappa dielectrics acting as a gate oxide is of particular interest in view of possible applications of semiconductor NWs in future wrap-gated field effect transistors (FETs). A high number of charged states at the NW-dielectrics interface can strongly degrade the performance of the FET which explains the strong interest in high quality deposition of high-kappa dielectrics. In the present work we show that time-resolved spectroscopy is a valuable and direct tool to monitor the surface quality of HfO(2)-capped InP NWs. In particular, we have studied the impact of ALD process parameters as well as surface treatment prior to the oxide capping on the NW-dielectrics interface quality. The best results in terms of the surface recombination velocity (S(0) = 9.5 x 10(3) cm s(-1)) were obtained for InP/GaP core/shell NWs in combination with a low temperature (100 degrees C) ALD process. While the present report focuses on the InP material system, our method of addressing the surface treatment for semiconductors with high-kappa dielectrics will also be applicable to nanoelectronic devices based on other III/V material systems such as InAs.

Control of the strong light-matter interaction between an elongated In_{0.3}Ga_{0.7}As quantum dot and a micropillar cavity using external magnetic fields.

We have studied a strongly coupled quantum dot-micropillar cavity system subject to an external magnetic field. The large diamagnetic response of elongated In_{0.3}Ga_{0.7}As quantum dots is exploited to demonstrate magneto-optical resonance tuning in the strong coupling regime. Furthermore, the magnetic field provides an additional degree of freedom to in situ manipulate the coupling constant. A transition from strong coupling towards the critical coupling regime is attributed to a reduction of the quantum dot oscillator strength when the magnetic confinement becomes significant with regards to the exciton confinement above 3 T.

The role of optical excitation power on the emission spectra of a strongly coupled quantum dot-micropillar system.

A strongly coupled quantum dot-micropillar cavity system is studied under variation of the excitation power. The characteristic double peak spectral shape of the emission with a vacuum Rabi splitting of 85 microeV at low excitation transforms gradually into a single broad emission peak when the excitation power is increased. Modelling the experimental data by a recently published formalism [Laussy et al., Phys. Rev. Lett. 101, 083601 (2008)] yields a transition from strong coupling towards weak coupling which is mainly attributed to an excitation power driven decrease of the exciton-photon coupling constant.

A Bayesian modeling approach for determining productivity regimes and their characteristics.

Oscillations in the environment result in substantial alterations to population dynamics as evidenced by time series of abundance and recruitment. Depending on the reference timescale, these oscillations are referred to as regime shifts. Regime shifts may occur on very short time scales and are often undetected for several years. Consequently, tools that allow the estimation of regime-specific population dynamic parameters may be of great value. Using a hidden Markov model to describe the unobserved regime state, we develop methods to infer regime-specific parameters for a commonly used model of density-dependent recruitment in addition to identifying the unobserved regime state. We apply the method to recruitment data for Japanese sardine (Sardinops melanostictus).

Isoform-specific increase of spastin stability by N-terminal missense variants including intragenic modifiers of SPG4 hereditary spastic paraplegia.

Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder selectively affecting axons of spinal cord motoneurons. Classical mutations in the most frequent HSP gene SPAST (spastin protein) act through haploinsufficiency by abolishing the activity of a C-terminal ATPase domain or by interfering with expression from the affected allele. N-terminal missense variants have been suggested to represent rare polymorphisms, to cause unusually mild phenotypes, and to aggravate the effect of a classical mutation. We confirm these associations for p.S44L but do not detect two other variants (p.E43Q; p.P45Q) in HSP patients and controls. We show that neither of several disease mechanisms associated with classical SPAST mutations applies to the N-terminal variants. Instead, all three alterations enhance the stability of one of two alternative spastin isoforms. Their phenotypic effect may thus not be mediated by haploinsufficiency but by increasing isoform competition for interacting proteins, substrates or oligomerization partners.

Transneuronally altered dendritic processing of tangle-free neurons in Alzheimer's disease.

In Alzheimer's disease (AD), changes in dendritic morphology can be regarded as a result of an inherent disease-specific process associated with the formation of neurofibrillary tangles. Using three-dimensional morphometrical techniques and neuropatholologically staged tissue (Braak classification) of 32 cases, we demonstrate alterations in the dendritic length, branch order and number of segments of a tangle-free neuronal population in the AD-afflicted hippocampus, i.e. parvalbumin-containing cells of the fascia dentata. These alterations occurred primarily on the apical dendritic tree, the target of the entorhinal input. Mean of relative dendritic length, branch order and number of dendritic segments of apical dendrites decreased significantly, by 40-70% comparing stage V to stages 0 or I. In contrast, basal dendrites receiving no entorhinal input did not show significant changes. Entorhinal neurons projecting to the hippocampus are the first to be affected in AD and the first to die, resulting in hippocampal deafferentation. Therefore, this input-specific dendritic alteration of tangle-free neurons suggests that AD is confounded with a transneuronal component resulting from deafferentation. Experiments showed that deafferentation results in altered dendritic geometry causing an impaired signal integration. Thus, transneuronally altered dendritic signal integration might occur in neurons devoid of the major intraneuronal hallmark of AD, i.e. the neurofibrillary tangle.

Impact of inhibition of complement by sCR1 on hepatic microcirculation after warm ischemia.

Recent observations provide evidence that complement is implicated as an important factor in the pathophysiology of ischemia/reperfusion injury (IRI). Here, we assessed the effects of complement inhibition on hepatic microcirculation by in vivo microscopy (IVM) using a rat model of warm hepatic ischemia clamping the left pedicle for 70 min. Ten animals received the physiological complement regulator soluble complement receptor type 1 (sCR1) intravenously 1 min prior to reperfusion. Controls were given an equal amount of Ringer's solution (n = 10). Microvascular perfusion and leukocyte adhesion were studied 30 to 100 min after reperfusion by IVM. Microvascular perfusion in hepatic sinusoids was significantly improved in the sCR1 group (80.6 +/- 0.6% of all observed sinusoids were perfused [sCR1] vs 67.3 +/- 1.2% [controls]). The number of adherent leukocytes was reduced in sinusoids (49.9 +/- 3.4 [sCR1] vs 312.3 +/- 14.2 in controls [adherent leukocytes per square millimeter of liver surface]; P < 0.001) as well as in postsinusoidal venules after sCR1 treatment (230.9 +/- 21.7 [sCR1] vs 1906.5 +/- 93.5 [controls] [adherent leukocytes per square millimeter of endothelial surface]; P < 0.001). Reflecting reduced hepatocyte injury, liver transaminases were decreased significantly upon sCR1 treatment compared to controls. Our results provide further evidence that complement plays a decisive role in warm hepatic IRI. Therefore, we conclude that complement inhibition by sCR1 is effective as a therapeutical approach to reduce microcirculatory disorders after reperfusion following warm organ ischemia.