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.

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 ).

[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.

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.

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.

[Common femoral artery bailout stenting with covered stent graft due to TAVR vascular complication: Clinical long term follow-up]. / Suivi clinique après implantation d'un stent couvert dans l'artère fémorale commune au décours immédiat d'une complication vasculaire per-TAVI.

BACKGROUND: Vascular complications are frequent in the context of transcatheter aortic valve replacement and may require the implantation of a covered stent graft in the common femforal artery. However, common femoral artery is considered to be at high risk of stent fracture or occlusion due to high mobility of the hip joint. PATIENTS AND METHODS: We analyzed medical records of patients with transcatheter aortic valve replacement related vascular complications between 2015 and 2018, treated with commom femoral artery transluminal angioplasty or surgery. Vascular complications or suspect symptoms were followed up by phone calls. RESULTS: Among 552 patients, 43 patients were included. Twelve (11.6 %) were managed by prolonged balloon inflation, 5 (11.6 %) by first line surgery and 26 (60.4 %) by the implantation of a covered stent graft. Among the latter group, the covered stent graft was efficient in 24 patients (92.3 %). The median follow-up was 430 days [3-1499]. The first-line surgery group had a higher risk of red blood cell transfusion and all causes mortality. At follow-up, no patient had suspicious symptoms of vascular covered stent complication. Four patients (9.3 %) had US-doppler or CT vascular imaging at follow-up, showing no evidence of stent fracture or occlusion. CONCLUSION: In our study, the implantation of a covered stent graft in the common femoral artery was an efficient and safe strategy for the management of transcatheter aortic valve replacement related vascular complications.

Molecular imaging with neural training of identification algorithm (neural network localization identification).

Superresolution localization microscopy strongly relies on robust identification algorithms for accurate reconstruction of the biological systems it is used to measure. The fields of machine learning and computer vision have provided promising solutions for automated object identification, but usually rely on well represented training sets to learn object features. However, using a static training set can result in the learned identification algorithm making mistakes on data that is not well represented by the training set. Here, we present a method for training an artificial neural network without providing a training set in advance. This method uses the data to be analyzed, and the fitting algorithm to train an artificial neural network tailored to that data set. We show that the same artificial neural network can learn to identify at least two types of molecular emissions: the regular point spread functions (PSFs), and the astigmatism PSF. Simulations indicate that this method can be extremely reliable in extracting molecular emission signatures. Additionally, we implemented the artificial neural network calculation to be performed on a graphics processing unit (GPU) for massively parallelized calculation which drastically reduces the time required for the identification process. By implementing the neural identification on a GPU, we allow this method of identification to be used in a real time analysis algorithm. RESEARCH HIGHLIGHTS: Here, we present a machine learning algorithm for identifying point-spread functions without the need for an a priori training set. We show that this method can detect over 90% of molecules with less than 1% false positive identification in simulations. We further show that because this algorithm does not make assumptions of about the shape of molecular emission, it is compatible with models beyond the symmetric 2D Gaussian.

Antibiotic resistant bacteria and resistance genes in the bottom sediment of a small stream and the potential impact of remobilization.

River sediments are regarded as hot spots of bacterial density and activity. Moreover, high bacterial densities and biofilm formation are known to promote horizontal gene transfer, the latter playing a vital role in the spread of antimicrobial resistance. It can thus be hypothesized that sediments act as a reservoir of antibiotic resistant bacteria (ARB) and resistance genes (ARGs), particularly in rivers receiving microbes and drug residues from treated sewage. We analyzed the phenotypic susceptibility of 782 Escherichia coli isolates against 24 antimicrobials and we measured the relative abundances of five ARGs in water and sediment extracts of a small stream. We did not find evidence for a general increase in the proportion of resistant E. coli isolated from sediments as compared to those found in stream water. For most antimicrobials, the likelihood of detecting a resistant isolate was similar in water and sediment or it was even lower in the latter compartment. The mean relative abundance of ARGs was moderately increased in sediment-borne samples. Generally, absolute abundances of resistant cells and resistance genes in the sediment exceeded the pelagic level owing to higher bacterial densities. The river bottom thus represents a reservoir of ARB and ARGs that can be mobilized by resuspension.

[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.

Decreased serum L-arginine and L-citrulline levels in major depression.

RATIONALE: It has been suggested that endothelial dysfunction caused by a decreased endothelial production of nitric oxide (NO) may contribute to the consistently observed increased risk of developing cardiovascular disease (CVD) in physically healthy patients suffering from major depression (MD). NO is a gas synthesized from Larginine (a conditionally essential amino acid) and oxygen by endothelial nitric oxide synthase (eNOS). The end products of NO production include both NO and L-citrulline. NO is rapidly reduced to the anions nitrite and nitrate, classically referred to as NO metabolites. Their measurement has been used as a surrogate measurement for endothelial NO production. We and others have shown decreased levels of NO metabolites in the serum of MD patients. The mechanism of this decreased production of NO by the endothelium has not yet been elucidated. OBJECTIVES: The purpose of this study is to assess serum levels of L-arginine and L-citrulline in patients with MD. METHODS: Levels of L-arginine and L-citrulline were measured in 35 unmedicated physically healthy MD patients and 36 healthy controls (HCs). RESULTS: L-arginine and L-citrulline concentrations were significantly lower in MD patients than in healthy controls (L-arginine, 73.54 + 21.53 µmol/L and 84.89 + 25.16, p = 0.04 µmol/L and L-citrulline 31.58 + 6.05 µmol/L and 35.19 + 6.85 µmol/L, p = 0.03, respectively). CONCLUSIONS: The decrease in L-arginine levels in MD patients is a possible explanation for the decrease in NO metabolites in MD patients and therefore may contribute, through endothelial dysfunction, to the increased CV risk associated with MD.

Community IntraVenous Antibiotic Study (CIVAS): protocol for an evaluation of patient preferences for and cost-effectiveness of community intravenous antibiotic services.

INTRODUCTION: Outpatient parenteral antimicrobial therapy (OPAT) is used to treat a wide range of infections, and is common practice in countries such as the USA and Australia. In the UK, national guidelines (standards of care) for OPAT services have been developed to act as a benchmark for clinical monitoring and quality. However, the availability of OPAT services in the UK is still patchy and until quite recently was available only in specialist centres. Over time, National Health Service (NHS) Trusts have developed OPAT services in response to local needs, which has resulted in different service configurations and models of care. However, there has been no robust examination comparing the cost-effectiveness of each service type, or any systematic examination of patient preferences for services on which to base any business case decision. METHODS AND ANALYSIS: The study will use a mixed methods approach, to evaluate patient preferences for and the cost-effectiveness of OPAT service models. The study includes seven NHS Trusts located in four counties. There are five inter-related work packages: a systematic review of the published research on the safety, efficacy and cost-effectiveness of intravenous antibiotic delivery services; a qualitative study to explore existing OPAT services and perceived barriers to future development; an economic model to estimate the comparative value of four different community intravenous antibiotic services; a discrete choice experiment to assess patient preferences for services, and an expert panel to agree which service models may constitute the optimal service model(s) of community intravenous antibiotics delivery. ETHICS AND DISSEMINATION: The study has been approved by the NRES Committee, South West-Frenchay using the Proportionate Review Service (ref 13/SW/0060). The results of the study will be disseminated at national and international conferences, and in international journals.

The health technology assessment of the compulsory accident insurance scheme of hand transplantation in Switzerland.

UNLABELLED: Recently the decision-making committee of the compulsory Swiss accident insurance scheme needed to make a basic decision as to whether to fund hand transplantation under that scheme or not. A Health Technology Assessment was commissioned to inform decision-making and gain experience with applicability of the method. The following were main findings from various domains. Compared with prosthesis fitting, the outcome of hand transplantation is satisfactory for function and sensibility. Complications due to immunosuppression are frequent, sometimes severe and potentially life-shortening. The direct medical costs over the entire life span calculated for a 35-year-old unilaterally amputated base case patient were CHF 528,600 (EUR 438,500) higher than for a prosthesis. There are challenging ethical, legal and organizational issues. The committee decided not to reimburse hand transplantation for ethical reasons. The Health Technology Assessment has been shown to be a useful tool for decision-making in the context of Swiss accident insurance. LEVEL OF EVIDENCE: IV.