Is animal welfare better on smaller dairy farms? Evidence from 3,085 dairy farms in Germany.

The structural change toward larger (dairy) farms is often criticized because it supposedly has a negative effect on farm animal welfare. We investigated this criticism using cross-sectional survey data from 3,085 German dairy farms. Even though our sample was a convenience sample, it closely resembled the diverse structures of dairy farming in Germany and covered a wide range of dairy farm sizes (7 to 2,900 cows per farm, mean 122). We developed an animal welfare index (AWI) in close consultation with experts along the dairy value chain (e.g., farm animal welfare scientists, farmers, dairy representatives). Regression results showed that larger farms tended to achieve a better AWI than smaller farms in our data set. However, the effect size was small. Nevertheless, in contrast to the widespread assumption in public discussion, larger dairy herds are not necessarily associated with poorer animal welfare. In all herd size classes, we found a large variation of AWI between herds. Although this study focused on the effect of herd size, it is not the only factor affecting animal welfare levels on individual farms. Other variables that we included in the regression to describe the AWI indicate that the knowledge and skills of the farm manager and the amount of time that farms can devote to animals have a positive effect on the AWI. However, as with herd size, the effect size of other explanatory variables was small in absolute terms.

Hospital volume-outcome relationship in total knee arthroplasty: a systematic review and dose-response meta-analysis.

PURPOSE: This systematic review and dose-response meta-analysis aimed to investigate the relationship between hospital volume and outcomes for total knee arthroplasty (TKA). METHODS: MEDLINE, Embase, CENTRAL and CINAHL were searched up to February 2020 for randomised controlled trials and cohort studies that reported TKA performed in hospitals with at least two different volumes and any associated patient-relevant outcomes. The adjusted effect estimates (odds ratios, OR) were pooled using a random-effects, linear dose-response meta-analysis. Heterogeneity was quantified using the I2-statistic. ROBINS-I and the GRADE approach were used to assess the risk of bias and the confidence in the cumulative evidence, respectively. RESULTS: A total of 68 cohort studies with data from 1985 to 2018 were included. The risk of bias for all outcomes ranged from moderate to critical. Higher hospital volume may be associated with a lower rate of early revision ≤ 12 months (narrative synthesis of k = 7 studies, n = 301,378 patients) and is likely associated with lower mortality ≤ 3 months (OR = 0.91 per additional 50 TKAs/year, 95% confidence interval [0.87-0.95], k = 9, n = 2,638,996, I2 = 51%) and readmissions ≤ 3 months (OR = 0.98 [0.97-0.99], k = 3, n = 830,381, I2 = 44%). Hospital volume may not be associated with the rates of deep infections within 1-4 years, late revision (1-10 years) or adverse events ≤ 3 months. The confidence in the cumulative evidence was moderate for mortality and readmission rates; low for early revision rates; and very low for deep infection, late revision and adverse event rates. CONCLUSION: An inverse volume-outcome relationship probably exists for some TKA outcomes, including mortality and readmissions, and may exist for early revisions. Small reductions in unfavourable outcomes may be clinically relevant at the population level, supporting centralisation of TKA to high-volume hospitals. LEVEL OF EVIDENCE: III. REGISTRATION NUMBER: The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO CRD42019131209 available at: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=131209 ).

[Acupuncture covered by statutory health insurance in Germany : An observational study based on claims data]. / Akupunktur als Leistung der gesetzlichen Krankenversicherung in Deutschland : Eine retrospektive Beobachtungstudie basierend auf Abrechnungsdaten.

BACKGROUND: The coverage for acupuncture for chronic lower back or knee pain by the statutory health insurance was introduced in 2007. The aim of this study was to investigate characteristics of patients and providers of acupuncture and temporal and regional trends in the utilization of acupuncture. METHODS: This retrospective observational study used anonymized statutory health insurance claims data from a sample of roughly four million subjects. The sample is representative of the German population regarding age and gender in 2013. RESULTS: Lower back pain was the most common coded indication (86%) for billing acupuncture. Women were more often treated with acupuncture than men; the mean age was 61.1 years. For 63% acupuncture was billed in 2014 for the first time, 37% already had an acupuncture treatment in 2012 or 2013. Premature termination (<6 sessions) was observed in 14% of all insurants receiving acupuncture for the first time in 2014 for knee pain and in 21% of those with back pain. Overall there was a statistically significant decrease in the utilization of acupuncture from 2008 to 2015. Regional differences between East and West Germany and city states were observed. Half of all acupuncture treatments in 2014 were provided by 11% of all physicians who billed acupuncture at least once. DISCUSSION: Higher utilization of acupuncture by women reflects the epidemiology of back and knee pain and their preference for alternative complementary medicine. On the one hand, the large proportion of patients treated repeatedly with acupuncture suggests perceived benefits. On the other hand, provision of acupuncture services is decreasing continuously and a relevant proportion of subjects are terminating treatment prematurely.

Gene expression in human adipose-derived stem cells: comparison of 2D films, 3D electrospun meshes or co-cultured scaffolds with two-way paracrine effects.

Finding the appropriate cues to trigger the desired differentiation is a challenge in tissue engineering when stem cells are involved. In this regard, three-dimensional environments are often compared to cells' two-dimensional culture behaviour (plastic culture dish). Here, we compared the gene expression pattern of human adipose-derived stem cells (ASC) seeded in a three-dimensional (3D) electrospun mesh and on a two-dimensional (2D) film - both of exactly the same material. Additionally, we conducted experiments with a scaffold floating above a film to investigate two-way paracrine effects (co-system). Electrospun meshes (3D scaffolds) and films (2D), consisting either of pristine poly-lactic-co-glycolic acid (PLGA) or of PLGA-containing dispersed amorphous calcium phosphate nanoparticles (PLGA/aCaP), were seeded with ASCs and cultured either in Dulbecco Minimum Essential Medium (DMEM) or in osteogenic medium. After two weeks, minimum stem cell criteria markers as well as typical markers for osteogenesis, endothelial cell differentiation, adipogenesis and chondrogenesis were analysed by quantitative real-time PCR. Interestingly, mostly osteogenic genes of cells seeded on 3D meshes were upregulated compared to those on 2D films, while stem cell markers seemed to be only slightly affected. Runx2 and osteocalcin showed an especially strong upregulation under all conditions, while most other factors analysed for 2D/3D changes were highly dependent on the material composition, the culture medium and on paracrine signalling effects. The beneficial 3D environment for stem cells found in many studies has therefore not to be attributed to the third dimension alone and should carefully be compared to 2D films fabricated of the same material. Furthermore, paracrine interactions triggering differentiation are not negligible.

Localization microscopy: mapping cellular dynamics with single molecules.

Resolution describes the smallest details within a sample that can be recovered by a microscope lens system. For optical microscopes detecting visible light, diffraction limits the resolution to ∼200-250 nm. In contrast, localization measures the position of an isolated object using its image. Single fluorescent molecules can be localized with an uncertainty of a few tens of nanometres, and in some cases less than one nanometre. Superresolution fluorescence localization microscopy (SRFLM) images and localizes fluorescent molecules in a sample. By controlling the visibility of the fluorescent molecules with light, it is possible to cause a sparse subset of the tags to fluoresce and be spatially separated from each other. A movie is acquired with a camera, capturing images of many sets of visible fluorescent tags over a period of time. The movie is then analysed by a computer whereby all of the single molecules are independently measured, and their positions are recorded. When the coordinates of a sufficient number of molecules are collected, an image can be rendered by plotting the coordinates of the localized molecules. The spatial resolution of these rendered images can be better than 20 nm, roughly an order of magnitude better than the diffraction limited resolution. The invention of SRFLM has led to an explosion of related techniques. Through the use of specialized optics, the fluorescent signal can be split into multiple detection channels. These channels can capture additional information such as colour (emission wavelength), orientation and three-dimensional position of the detected molecules. Measurement of the colour of the detected fluorescence can allow researchers to distinguish multiple types of fluorescent tags and to study the interaction between multiple molecules of interest. Three-dimensional imaging and determination of molecular orientations offer insight into structural organization of the sample. SRFLM is compatible with living samples and has helped to illuminate many dynamic biological processes, such as the trajectories of molecules within living cells. This review discusses the concept and process of SRFLM imaging and investigates recent advances in SRFLM functionality. Since its announcement in 2006, SRFLM has been quickly adopted and modified by many researchers to help investigate questions whose answers lie below the diffraction limit. The versatility of the SRFLM technique has great promise for improving our understanding of cell biology at the molecular level.

Electron- and proton-impact excitation of hydrogenlike uranium in relativistic collisions.

The K shell excitation of H-like uranium (U(91+)) in relativistic collisions with different gaseous targets has been studied at the experimental storage ring at GSI Darmstadt. By performing measurements with different targets as well as with different collision energies, we were able to observe for the first time the effect of electron-impact excitation (EIE) process in the heaviest hydrogenlike ion. The large fine-structure splitting in H-like uranium allowed us to unambiguously resolve excitation into different L shell levels. State-of-the-art calculations performed within the relativistic framework which include excitation mechanisms due to both protons (nucleus) and electrons are in good agreement with the experimental findings. Moreover, our experimental data clearly demonstrate the importance of including the generalized Breit interaction in the treatment of the EIE process.

Low-cost 3D-printed anthropomorphic cardiac phantom, for computed tomography automatic left ventricle segmentation and volumetry - A pilot study.

INTRODUCTION: Accurate cardiac left ventricle (LV) delineation is essential to CT-derived left ventricular ejection fraction (LVEF). To evaluate dose-reduction potential, an anatomically accurate heart phantom, with realistic X-ray attenuation is required. We demonstrated and tested a custom-made phantom using 3D-printing, and examined the influence of image noise on automatically measured LV volumes METHODS: A single coronary CT angiography (CCTA) dataset was segmented and converted to Standard Tessellation Language (STL) mesh, using open-source software. A 3D-printed model, with hollow left heart chambers, was printed and cavities filled with gelatinized contrast media. This was CT-scanned in an anthropomorphic chest phantom, at different exposure conditions. LV and "myocardium" noise and attenuation was measured. LV volume was automatically measured using two different methods. We calculated Spearmans' correlation of LV volume with noise and contrast-noise ratio respectively om 486 scans of the phantom. Source images were compared to one phantom series with similar parameters. This was done using Dice coefficient on LV short-axis segmentations. RESULTS: Phantom "Myocardium" and LV attenuation was comparable to measurements on source images. Automatic volume measurement succeeded, with mean volume deviation to patient images less than 2 ml. There was a moderate correlation of volume with CNR, and strong correlation of volume with image noise. With papillary muscles included in LV volume, the correlation was positive, but negative when excluded. Variation of volumes was lowest at 90-100 kVp for both methods in the 486 repeat scans. The Dice coefficient was 0.87, indicating high overlap between the single phantom series and source scan. Cost of 3D-printer and materials was 400 and 30 Euro respectively. CONCLUSION: Both anatomically and radiologically the phantom mimicked the source scans closely. LV volumetry was reliably performed with automatic algorithms. IMPLICATIONS FOR PRACTICE: Patient-specific cardiac phantoms may be produced at minimal cost and can potentially be used for other anatomies and pathologies. This enables radiographic phantom studies without need for dedicated 3D-labs or expensive commercial phantoms.

Polarization transfer of bremsstrahlung arising from spin-polarized electrons.

We report on a study of the polarization transfer between transversely polarized incident electrons and the emitted x rays for electron-atom bremsstrahlung. By means of Compton polarimetry we performed for the first time an energy-differential measurement of the complete properties of bremsstrahlung emission related to linear polarization, i.e., the degree of linear polarization as well as the orientation of the polarization axis. For the high-energy end of the bremsstrahlung continuum the experimental results for both observables show a high sensitivity on the initial electron spin polarization and prove that the polarization orientation is virtually independent of the photon energy.

Human herpesvirus 6 in biopsies from patients with gastrointestinal symptoms after allogeneic stem cell transplantation.

Gastrointestinal complications are frequent after allogeneic stem cell transplantation (allo-SCT). Main differential diagnoses are graft-versus-host disease (GvHD) and viral infections. In this retrospective analysis, we included 50 patients with severe vomiting or diarrhea in the first year after allo-SCT. One hundred two biopsies obtained by colonoscopy or endoscopy of the upper gastrointestinal tract were analysed by conventional histology for signs of GvHD and by qualitative polymerase chain reaction (PCR) for viral DNA of human herpesvirus 6 (HHV-6) and other virus of the herpes family. DNA of HHV-6 was detected in 38 of 75 initial samples (51%) and in 19 of 27 follow-up biopsies (70%). In the initial samples (n = 75), HHV-6 DNA was detected in 20/37 (54%) biopsies in the presence of GvHD compared to 18/38 (47%) biopsies without signs of GvHD. At the time of the first endoscopic investigation, most patients received antiviral prophylaxis with aciclovir. None of the follow-up biopsies was HHV-6 DNA negative after antiviral treatment with aciclovir, foscarnet or ganciclovir. By univariate analysis, no risk factor for HHV-6 detection could be demonstrated. In this cohort of patients with severe gastrointestinal complications, there was no significant difference in the overall survival between patients with or without HHV-6 DNA detection in the gastrointestinal tract. In summary, the detection of HHV-6 DNA had no impact on overall survival. Moreover, antiviral therapy against HHV-6 was without effect. Thus, positive PCR results in GI tract samples do not necessarily reflect reactivation of HHV-6. Further studies are needed to define the significance of HHV-6 for GI tract symptoms after allo-SCT.

Infantile thiamine deficiency in South and Southeast Asia: An age-old problem needing new solutions.

Infantile beriberi, a potentially fatal disorder caused by thiamine deficiency, is often viewed as a disease confined to history in regions of the world with predominant white rice consumption. Recent case reports have, however, highlighted the persistence of thiamine deficiency as a cause of infant mortality in South and Southeast Asia. Low infant thiamine status and incidence of beriberi is attributable to maternal thiamine deficiency and insufficient breast milk thiamine. Poor dietary diversity, food preparation and cooking practices and traditional post-partum food restrictions likely play a role in these high-risk regions. Given the contribution of thiamine deficiency to infant mortality and emerging evidence of long-lasting neurodevelopmental deficits of severe and even subclinical deficiency in early life, public health strategies to prevent thiamine deficiency are urgently needed. However, efforts are hampered by uncertainties surrounding the identification and assessment of thiamine deficiency, due to the broad non-specific clinical manifestations, commonly referred to as thiamine deficiency disorders (TDD), that overlap with other conditions resulting in frequent misdiagnosis and missed treatment opportunities, and secondly the lack of readily available and agreed upon biomarker analysis and cut-off thresholds. This review will discuss the key challenges and limitations in the current understanding of TDD and explore how ongoing initiatives plan to fill persistent knowledge gaps, namely in the development of a standardised case definition to help more accurately diagnose and treat TDD in low-resource settings. Given more attention and ensuring greater recognition of TDD will support the design and implementation of treatment and prevention programmes, and ensure beriberi can truly be considered 'the forgotten disease of Asia'.

Value of regular endosonography and [18F]fluorodeoxyglucose PET-CT after surgery for gastro-oesophageal junction, stomach or pancreatic cancer.

BACKGROUND: Most patients undergo follow-up after surgery for cancers of the gastro-oesophageal junction, stomach or pancreas, but data to support which modalities to use and the frequency of investigation are limited. METHODS: Patients in the EUFURO study were randomized to either visits to the outpatient clinic at 3, 6, 9, 12, 18, and 24 months after surgery (standard), or to the addition of [18F]fluorodeoxyglucose (FDG) PET-CT and endoscopic ultrasonography (EUS) with guided fine-needle aspiration biopsy to clinical assessments (intervention). Data from the intervention arm were used to analyse the diagnostic performance of endosonography or [18F]FDG PET-CT in detecting recurrences. RESULTS: During the scheduled follow-up, 42 of 89 patients developed recurrence; PET-CT and EUS in combination detected 38 of these recurrences. EUS detected 23 of the 42 patients with recurrent disease during follow-up and correctly diagnosed 17 of 19 locoregional recurrences. EUS was able to detect isolated locoregional recurrence in 11 of 13 patients. In five patients, EUS was false-positive for isolated locoregional recurrence owing to missed distant metastases. PET-CT detected locoregional recurrence in only 12 of 19 patients, and isolated locoregional recurrence in only 7 of 13. False-positive PET-CT results in 23 patients led to a total of 44 futile procedures. CONCLUSION: Accuracy in detecting recurrences by concomitant use of PET-CT and EUS was high (90 per cent). PET-CT had moderate to high sensitivity for overall recurrence detection, but low specificity. EUS was superior to PET-CT in the detection of locoregional and isolated locoregional recurrences.

[Challenges of coronary catheterization after TAVR]. / Difficultés de cathétérisme coronaire après TAVI.

PURPOSE: Coronary catheterization after transcatheter aortic valve implantation (TAVR) may be challenging. The main objective of the study is to assess the feasibility of coronary catheterization and angioplasty according to each type of valve. PATIENTS AND METHOD: We retrospectively studied coronary angiography or percutaneous angioplasty procedures after TAVR in two different centers. The catheterization success of coronary artery was evaluated according to the quality of engagement in ostium and opacification of the artery. Other indicators were collected including catheters used, fluoroscopy and angiography times, DAP and the volume of the contrast agent. RESULTS: Among 1512 TAVR procedures, 33 patients were included. The Sapien 3® valve was implanted in 22 patients and the Evolut® in 11 patients (7 Evolut-R® and 4 Evolut Pro®). Coronary angiography with selective or partially selective catheterization has been successfully performed in all patients with a Sapien 3® valve. In the Evolut® group we identified 3 cases of non-selective catheterization for the right coronary and 1 case for the left coronary. Standard Judkins catheters seem to be the most suitable for both types of valve with very good efficiency. CONCLUSION: The results of our study is promising for the future of TAVR with a coronary catheterization success rate close to 100% with some difficulties for the Evolut® supra-annular valves. Special attention should be paid to the technique of implantation and orientation of cups in the aortic sinus.

Effects of suspended coal particles on gill structure and oxygen consumption rates in a coral reef fish.

Large quantities of coal are transported through tropical regions; however, little is known about the sub-lethal effects of coal contamination on tropical marine organisms, including fish. Here, we measured aerobic metabolism and gill morphology in a planktivorous coral reef damselfish, Acanthochromis polyacanthus to elucidate the sub-lethal effects of suspended coal particles over a range of coal concentrations and exposure durations. Differences in the standard oxygen consumption rates (MO2) between control fish and fish exposed to coal particles (38 and 73 mg L-1) were minimal and generally not dose dependent; however, the MO2 of fish exposed to 38 mg coal L-1 (21 days) and 73 mg coal L-1 (31 days) were both significantly higher than the MO2 of control fish. Chronic coal exposure (31 days) altered gill structure in the higher coal treatments (73 and 275 mg L-1), with fish exposed to 275 mg L-1 exhibiting significant reductions in gill mucous and thinning of lamellar and filament epithelium. These findings contribute to our limited understanding of the potential impacts of coal on tropical reef species; however, most of the observed effects occurred at high coal concentrations that are unlikely under most coal spill scenarios. Future studies should investigate other contamination scenarios such as the impacts of chronic exposures to lower concentrations of coal.

A novel function of CD40: induction of cell death in transformed cells.

CD40 is known as an important T-B cell interaction molecule which rescues B lymphocytes from undergoing apoptosis. Like other receptors of the tumor necrosis factor (TNF) receptor gene family, CD40 is expressed on cells of different tissue origins including some transformed cells. In contrast to its well-studied effects on B cells, the biological functions of CD40 in non-immune cells remain largely unknown. Here we show that CD40 ligation induces apoptotic cell death in transformed cells of mesenchymal and epithelial origin. This CD40-mediated cell death seems to use a preformed signaling pathway since it occurs even when protein synthesis is blocked. Notably, the CD40 cytoplasmic domain shares a structural homology with the recently defined "death domains" of the 55-kD TNF receptor (p55TNFR) and Fas. Despite these structural similarities, differences are seen in the way phorbol myristate acetate, interleukin 1, TNF, and various metabolic inhibitors influence the cellular responsiveness to CD40, p55TNFR, and Fas-mediated killing. Our study indicates that CD40 induces cell death by a distinct mechanism.

Direct determination of the magnetic quadrupole contribution to the Lyman-α1 transition in a hydrogenlike ion.

We report the observation of an interference between the electric dipole (E1) and the magnetic quadrupole (M2) amplitudes for the linear polarization of the Ly-α1 (2p3/2→1s1/2) radiation of hydrogenlike uranium. This multipole mixing arises from the coupling of the ion to different multipole components of the radiation field. Our observation indicates a significant depolarization of the Ly-α1 radiation due to the E1-M2 amplitude mixing. It proves that a combined measurement of the linear polarization and of the angular distribution enables a very precise determination of the ratio of the E1 and the M2 transition amplitudes and the corresponding transition rates without any assumptions concerning the population mechanism for the 2p3/2 state.

Spectral shape of the two-photon decay of the 2 1S0 state in he-like tin.

The spectral distribution of the 1s2s {1}S{0}-->1s{2} 1S0 two-photon decay of He-like tin was measured using a novel approach at the gas-jet target of the ESR storage ring. Relativistic collisions of Li-like projectiles with low-density gaseous matter have been exploited to selectively populate the desired 1s2s state. Compared to conventional techniques, this approach results in a substantial gain in statistical and systematic accuracy, which allowed us to achieve for the first time a sensitivity to relativistic effects on the two-photon decay spectral shape as well as to discriminate the measured spectrum for Sn from theoretical shapes for different elements along the He-isoelectronic sequence.

Maternal high-fat diet during lactation reprograms the dopaminergic circuitry in mice.

The maternal perinatal environment modulates brain formation, and altered maternal nutrition has been linked to the development of metabolic and psychiatric disorders in the offspring. Here, we showed that maternal high-fat diet (HFD) feeding during lactation in mice elicits long-lasting changes in gene expression in the offspring's dopaminergic circuitry. This translated into silencing of dopaminergic midbrain neurons, reduced connectivity to their downstream targets, and reduced stimulus-evoked dopamine (DA) release in the striatum. Despite the attenuated activity of DA midbrain neurons, offspring from mothers exposed to HFD feeding exhibited a sexually dimorphic expression of DA-related phenotypes, i.e., hyperlocomotion in males and increased intake of palatable food and sucrose in females. These phenotypes arose from concomitantly increased spontaneous activity of D1 medium spiny neurons (MSNs) and profoundly decreased D2 MSN projections. Overall, we have unraveled a fundamental restructuring of dopaminergic circuitries upon time-restricted altered maternal nutrition to induce persistent behavioral changes in the offspring.

A functional role for GTP-binding proteins in synaptic vesicle cycling.

The squid giant synapse was used to test the hypothesis that guanosine-5'-triphosphate (GTP)-binding proteins regulate the local distribution of synaptic vesicles within nerve terminals. Presynaptic injection of the nonhydrolyzable GTP analog GTP gamma S irreversibly inhibited neurotransmitter release without changing either the size of the calcium signals produced by presynaptic action potentials or the number of synaptic vesicles docked at presynaptic active zones. Neurotransmitter release was also inhibited by injection of the nonhydrolyzable guanosine diphosphate (GDP) analog GDP beta S but not by injection of AIF4-. These results suggest that a small molecular weight GTP-binding protein directs the docking of synaptic vesicles that occurs before calcium-dependent neurotransmitter release. Depletion of undocked synaptic vesicles by GTP gamma S indicates that additional GTP-binding proteins function in the terminal at other steps responsible for synaptic vesicle replenishment.

Early meteorological results from the viking 2 lander.

Early results from the meteorological instruments on the Viking 2 lander are presented. As on lander 1, the daily patterns of temperature, wind, and pressure have been highly repetitive during the early summer period. The average daily maximum temperature was 241 degrees K and the diurnal minimum was 191 degrees K. The wind has a vector mean of 0.7 meter per second from the southeast with a diurnal amplitude of 3 meters per second. Pressure exhibits both diurnal and semidiurnal oscillations, although of substantially smaller amplitude than those of lander 1. Departures from the repetitive diurnal patterns begin to appear on sol 37.