Effect of solution treatment on the microstructure,phase transformation behavior and functional properties of NiTiNb ternary shape memory alloys fabricated via laser powder bed fusion in-situ alloying

Post-heat treatment is commonly employed to improve the microstructural homogeneity and enhance the mechanical performances of the additively manufactured metallic materials.In this work,a ternary(NiTi)91Nb9(at.%)shape memory alloy was produced by laser powder bed fusion(L-PBF)using pre-alloyed NiTi and elemental Nb powders.The effect of solution treatment on the microstructure,phase transformation behavior and mechanical/functional performances was investigated.The in-situ alloyed(NiTi)91Nb9 alloy exhibits a submicron cellular-dendritic structure surrounding the supersaturated B2-NiTi matrix.Upon high-temperature(1273 K)solution treatment,Nb-rich precipitates were precipitated from the supersaturated matrix.The fragmentation and spheroidization of the NiTi/Nb eutectics occurred during solution treatment,leading to a morphological transition from mesh-like into rod-like and sphere-like.Coarsening of theβ-Nb phases occurred with increasing holding time.The martensite transformation temperature increases after solution treatment,mainly attributed to:(i)reduced lattice distortion due to the Nb expulsion from the supersaturated B2-NiTi,and(ii)the Ti expulsion from theβ-Nb phases that lowers the ratio Ni/Ti in the B2-NiTi matrix,which resulted from the microstructure changes from non-equilibrium to equilibrium state.The thermal hysteresis of the solutionized alloys is around 145 K after 20%pre-deformation,which is comparable to the conventional NiTiNb alloys.A short-term solution treatment(i.e.at 1273 K for 30 min)enhances the ductility and strength of the as-printed specimen,with the increase of fracture stress from(613±19)MPa to(781±20)MPa and the increase of fracture strain from(7.6±0.1)%to(9.5±0.4)%.Both the as-printed and solutionized samples exhibit good tensile shape memory effects with recovery rates>90%.This work suggests that post-process heat treatment is essential to optimize the microstructure and improve the mechanical performances of the L-PBF in-situ alloyed parts.

Medical Curriculum at KU Leuven-University of Leuven, Belgium

In this paper we reflect on the evolution of medical education, with the medical curriculum at the University of Leuven as a concrete example. Formally, the Leuven curriculum follows a bachelor's and master's structure that leads to the degree of Medical Doctor after which further advanced training is required to become a practising physician. The Leuven curriculum takes the CanMEDS model as its educational framework. Embedding the CanMEDs roles within the curriculum is achieved using four learning pathways(Knowledge and Fundamentals of Medicine; Scientific Training; The Physician in Society; Skills and Communication) that run across the bachelor's and master's programmes. A stepwise approach is adopted whereby students progressively acquire the required competences to translate medical knowledge into evidence-based clinical practice. The learning process initially takes place in a simple and controlled environment, e.g. lectures or demonstrations with(simulated) patients. As the programme progresses, learning and assessment occur in ever more authentic medical situations,e.g. during the clerkships. In the future it will be important to capture new developments in e.g. education technology, health care organisation and patient involvement, and incorporate them into the medical curriculum. In this way we may fulfil our ambition to train medical doctors that are ready to participate in the 21^(st) century health care system and take their responsibility towards both the individual patient and public health care.

Experimental investigation of railway train-induced vibrations of surrounding ground and a nearby multi-story building

In this paper, a field experiment was carried out to study train-induced environmental vibrations. During the field experiment, velocity responses were measured at different locations of a six-story masonry structure near the Beijing- Guangzhou Railway and along a small road adjacent to the building. The results show that the velocity response levels of the environmental ground and the building floors increase with train speed, and attenuate with the distance to the railway track. Heavier freight trains induce greater vibrations than lighter passenger trains. In the multi-story building, the lateral velocity levels increase monotonically with floor elevation, while the vertical ones increase with floor elevation in a fluctuating manner. The indoor floor vibrations are much lower than the outdoor ground vibrations. The lateral vibration of the building along the direction of weak structural stiffness is greater than along the direction with stronger stiffness. A larger room produces greater floor vibrations than the staircase at the same elevation, and the vibration at the center of a room is greater than at its corner. The vibrations of the building were compared with the Federal Transportation Railroad Administration （FTA） criteria for acceptable ground-borne vibrations expressed in terms ofrms velocity levels in decibels. The results show that the train-induced building vibrations are serious, and some exceed the allowance given in relevant criterion.

Behaviour of layered sandstone under Brazilian test conditions:Layer orientation and shape effects

The experimental study in this paper focuses on the effects of the layer orientation and sample shape on failure strength and fracture pattern of samples tested under Brazilian test conditions(i.e.diametrical loading of cylindrical discs)for one particular layered sandstone which is from Modave in the south of Belgium.The variations of the strength in combination with the failure patterns are examined as a function of the inclination angle between the layer plane and the loading direction.The experimental,results clearly show that the induced fracture patterns are a combination of tensile and/or shear fractures.In shape effect experiments the layer thickness and the number of layer boundaries are investigated.Different blocks of Modave sandstone are used to prepare samples.The layer thickness is different among the various blocks,but the layer thickness in each studied rock block can be considered to be constant;hence,the number of layer boundaries changes according to the sample diameter for samples of the same block.The experimental study shows that the layer thickness plays a more important role than the number of layer boundaries per sample.

Endoscopic management of Crohn's strictures

Symptomatic intestinal strictures develop in more than one third of patients with Crohn's disease(CD) within 10 years of disease onset. Strictures can be inflammatory, fibrotic or mixed and result in a significant decline in quality of life, frequently requiring surgery for palliation of symptoms. Patients under the age of 40 with perianal disease are more likely to suffer from disabling ileocolonic disease thus may have a greater risk for fibrostenotic strictures. Treatment options for fibrostenotic strictures are limited to endoscopic and surgical therapy. Endoscopic balloon dilatation(EBD) appears to be a safe, less invasive and effective alternative modality to replace or defer surgery. Serious complications are rare and occur in less than 3% of procedures. For non-complex strictures without adjacent fistulizaation or perforation that are less than 5 cm in length, EBD should be considered as first-line therapy. The aim of this review is to present the current literature on the endoscopic management of small bowel and colonic strictures in CD, which includes balloon dilatation, adjuvant techniques of intralesional injection of steroids and anti-tumor necrosis factor, and metal stent insertion. Short and long-term outcomes, complications and safety of EBD will be discussed.

Structural elucidation of SARS-CoV-2 vital proteins: Computational methods reveal potential drug candidates against main protease, Nsp12 polymerase and Nsp13 helicase

Recently emerged SARS-CoV-2 caused a major outbreak of coronavirus disease 2019(COVID-19)and instigated a widespread fear,threatening global health safety.To date,no licensed antiviral drugs or vaccines are available against COVID-19 although several clinical trials are under way to test possible therapies.During this urgent situation,computational drug discovery methods provide an alternative to tiresome high-throughput screening,particularly in the hit-to-lead-optimization stage.Identification of small molecules that specifically target viral replication apparatus has indicated the highest potential towards antiviral drug discovery.In this work,we present potential compounds that specifically target SARS-CoV-2 vital proteins,including the main protease,Nsp12 RNA polymerase and Nsp13 helicase.An integrative virtual screening and molecular dynamics simulations approach has facilitated the identification of potential binding modes and favourable molecular interaction profile of corresponding compounds.Moreover,the identification of structurally important binding site residues in conserved motifs located inside the active site highlights relative importance of ligand binding based on residual energy decomposition analysis.Although the current study lacks experimental validation,the structural information obtained from this computational study has paved way for the design of targeted inhibitors to combat COVID-19 outbreak.

Functional brain imaging of gastrointestinal sensation in health and disease

It has since long been known, from everyday experience as well as from animal and human studies, that psychological processes-both affective and cognitive- exert an influence on gastrointestinal sensorimotor function. More specifically, a link between psychological factors and visceral hypersensitivity has been suggested, mainly based on research in functional gastrointestinal disorder patients. However, until recently, the exact nature of this putative relationship remained unclear, mainly due to a lack of non-invasive methods to study the （neurobiological） mechanisms underlying this relationship in non-sleeping humans. As functional brain imaging, introduced in visceral sensory neuroscience some 10 years ago, does provide a method for in vivo study of brain-gut interactions, insight into the neurobiological mechanisms underlying visceral sensation in general and the influence of psychological factors more particularly, has rapidly grown. In this article, an overview of brain imaging evidence on gastrointestinal sensation will be given, with special emphasis on the brain mechanisms underlying the interaction between affective ＆ cognitive processes and visceral sensation. First, the reciprocal neural pathways between the brain and the gut （brain- gut axis） will be briefly outlined, including brain imaging evidence in healthy volunteers. Second, functional brain imaging studies assessing the influence of psychological factors on brain processing of visceral sensation in healthy humans will be discussed in more detail. Finally, brain imaging work investigating differences in brain responses to visceral distension between healthy volunteers and functional gastrointestinal disorder patients will be highlighted.

Total Replacement of Fish Oil with Vegetable Oils in the Diet of Juvenile Jade Perch Scortum barcoo Reared in Recirculating Aquaculture Systems

To determine the replacement of fish oil with vegetable oils in the diet of juvenile Jade perch Scortum barcoo, four feeds with each a different oil （fish, sunflower, linseed and a mixture of 75% canola and 25% linseed oil）, were fed to Jade perch reared in recirculating aquaculture systems （RAS）. The trial lasted for 10 weeks and the fatty acid （FA） profile of both feed and fish muscle tissue were examined. There was no difference in growth, feed conversion rate （FCR） and mortality. The fish grew from 10 g to 110 g with a FCR of 1.25 and 0 mortality. The FA profile of the fish muscle tissue reflected the FA profile of the feed. The flesh of the fish that were fed the linseed oil diet, were extremely high in omega-3 （n-3） polyunsaturated FA （n-3 PUFA） with 3.75% of wet weight. This is one of the highest concentrations of n-3 PUFA ever recorded in fish flesh. In a finishing feeding test, the remaining vegetable oil fed fish were fed the fish oil diet for another two weeks immediately after the 10 weeks trial, to check for a possible recovery of n-3 highly unsaturated fatty acids （HUFA）. The wash out rate of FA towards n-3 HUFA in the muscle tissue was about 25% over this two weeks period.

Changes of gastric ulcer bleeding in the metropolitan area of Japan

BACKGROUND The two main causes of gastric ulcer bleeding are Helicobacter pylori(H.pylori)infection and ulcerogenic medicines,although the number of cases caused by each may vary with age.In Japan,the rate of H.pylori infection has fallen over the last decade and the number of prescriptions for non-steroidal anti-inflammatory drugs(NSAIDs)and antithrombotic drugs is increasing as the population ages.Methods of treatment for gastric ulcer bleeding have advanced with the advent of hemostatic forceps and potassium-competitive acid blocker(P-CAB).Thus,causes and treatments for gastric ulcer bleeding have changed over the last decade.AIM To examine the trends of gastric ulcer bleeding over 10 years in the metropolitan area of Japan.METHODS This is a single-center retrospective study.A total of 564 patients were enrolled from inpatients admitted to our hospital with gastric ulcer bleeding between 2006 and 2016.Age,medication history,H.pylori infection,method of treatment,rate of rebleeding,and the length of hospitalization were analyzed.Factors associated with gastric ulcer bleeding were evaluated using Fisher’s exact test,Pearson’s Chi-squared test or Student’s t-test as appropriate.The Jonckheere-Terpstra test was used to evaluate trends.A per-protocol analysis was used to examine the rate of H.pylori infection.RESULTS There was a significant increase in the mean age over time(P<0.01).The rate of H.pylori infection tended to decrease over the study period(P=0.10),whereas the proportion of patients taking antithrombotic agents or NSAIDs tended to increase(P=0.07).Over time,the use of NSAIDs and antithrombotic drugs increased with age.By contrast,the rate of H.pylori infection during the study period fell with age.H.pylori-induced ulcers accounted for the majority of cases in younger patients(<70 years old);however,the rate decreased with age(P<0.01).The method of treatment trend has changed significantly over time.The main method of endoscopic hemostasis has changed from clipping and injection to forceps coagulation(P<0.01),and frequently prescribed medicines have changed from proton pump inhibitor to P-CAB(P<0.01).The rate of rebleeding during the latter half of the study was significantly lower than that in the first half.CONCLUSION These trends,gastric ulcers caused by ulcerogenic drugs were increasing with age and H.pylori-induced ulcers were more common in younger patients,were observed.

Structural and functional aspects of the liver and liver sinusoidal cells in relation to colon carcinoma metastasis

Nowadays, liver metastasis remains difficult to cure. When tumor cells escape and arrive in the liver sinusoids, they encounter the local defense mechanism specific to the liver. The sinusoidal cells have been widely described in physiologic conditions and in relation to metastasis during the past 30 years. This paper provides an “overview” of how these cells function in health and in diseases such as

Validation of a novel imaging approach using multi-slice CT and cone-beam CT to follow-up on condylar remodeling after bimaxillary surgery

The main goal of this study was to introduce a novel three-dimensional procedure to objectively quantify both inner and outer condylar remodelling on preoperative multi-slice computed tomography （MSCT） and postoperative cone-beam computed tomography （CBCT） images. Second, the reliability and accuracy of this condylar volume quantification method was assessed. The mandibles of 20 patients （11 female and 9 male） who underwent bimaxillary surgery were semi-automatically extracted from MSCT/CBCT scans and rendered in 3D. The resulting condyles were spatially matched by using an anatomical landmark-based registration procedure. A standardized sphere was created around each condyle, and the condylar bone volume within this selected region of interest was automatically calculated. To investigate the reproducibility of the method, inter- and intra-observer reliability was calculated for assessments made by two experienced radiologists twice five months apart in a set of ten randomly selected patients. To test the accuracy of the bone segmentation, the inner and outer bone structures of one dry mandible, scanned according to the clinical set-up, were compared with the gold standard, micro-CT. Thirty-eight condyles showed a significant （P〈O.05） mean bone volume decrease of 26.4%_ 11.4% （502.9 mm3＋ 268.1 mm3）. No significant effects of side, sex or age were found. Good to excellent （ICC〉 0.6） intra- and inter-observer reliability was observed for both MSCT and CBCT. Moreover, the bone segmentation accuracy was less than one voxel （0.4 mm） for MSCT （0.3 mm __. 0.2 mm） and CBCT （0.4 mm _ 0.3 mm）, thus indicating the clinical potential of this method for objective follow-up in pathological condylar resorption.

Gelatin degradation assay reveals MMP-9 inhibitors and function of O-glycosylated domain

AIM: To establish a novel, sensitive and high-throughput gelatinolytic assay to define new inhibitors and compare domain deletion mutants of gelatinase B/matrix metalloproteinase (MMP)-9. METHODS: Fluorogenic Dye-quenched (DQ)TM-gelatin was used as a substrate and biochemical parameters (substrate and enzyme concentrations, DMSO solvent concentrations) were optimized to establish a highthroughput assay system. Various small-sized libraries (ChemDiv, InterBioScreen and ChemBridge) of hetero-cyclic, drug-like substances were tested and compared with prototypic inhibitors. RESULTS: First, we designed a test system with gelatin as a natural substrate. Second, the assay was validated by selecting a novel pyrimidine-2,4,6-trione (barbitu- rate) inhibitor. Third, and in line with present structural data on collagenolysis, it was found that deletion of the O-glycosylated region significantly decreased gelatinolytic activity (kcat/kM ± 40% less than full-length MMP-9). CONCLUSION: The DQTM-gelatin assay is useful in high-throughput drug screening and exosite targeting. We demonstrate that flexibility between the catalytic and hemopexin domain is functionally critical for gelatinolysis.

A review of high-performance MEMS sensors for resource exploration and geophysical applications

MEMS sensors have the advantages of small volume,lightweight,and low cost,therefore,have been widely used in the fields of consumer electronics,industry,health,defence,and aerospace.With their ever-improving performance,MEMS sensors have also started to be used in resource exploration and geophysical applications.However,the requirements of high-precision MEMS sensors for geophysical applications have not been specified in detail.Therefore,this paper systematically analyzes the requirements of high-performance MEMS sensors for prospecting and geophysical applications,including seismic surveillance,Earth tide,volcanic activity monitoring for natural disasters;seismic,gravity,and magnetic resource prospecting;drilling process monitoring and local gravity measurement for gravity aided navigation.Focusing on the above applications,this paper summarizes the state-of-the-art of research on high-performance MEMS sensors for resource exploration and geophysical applications.Several off-the-shelf MEMS sensors have been used for earthquake monitoring,seismic exploration and drilling process monitoring,and a range of MEMS research prototype sensors have successfully been employed for Earth tides measurement and are promising to be used for gravity exploration.MEMS magnetometers should have a lower noise floor to meet the demand for magnetic exploration.MEMS gravity gradiometers are still under early development and will not be deployable in short-term.Highperformance MEMS sensors hold the advantages of low-cost,high integration,and capability of working in extreme environments;therefore,they are likely to gradually replace some conventional geophysical instruments in some application areas.

Treatment of severe steroid refractory ulcerative colitis

Although systemic steroids are highly efficacious in ulcerative colitis (UC), failure to respond to steroids still poses an important challenge to the surgeon and physician alike. Even if the life time risk of a fulminant UC flare is only 20%, this condition is potentially life threatening and should be managed in hospital. If patients fail 3 to 5 d of intravenous corticosteroids and optimal supportive care, they should be considered for any of three options: intravenous cyclosporine (2 mg/kg for 7 d, and serum level controlled), infliximab (5 mg/kg Ⅳ, 0-2-6 wk) or total colectomy. The choice between these three options is a medical- surgical decision based on clinical signs, radiological and endoscopic findings and blood analysis (CRP, serum albumin). Between 65 and 85% of patients will initially respond to cyclosporine and avoid colectomy on the short term. Over 5 years only 50% of initial responders avoid colectomy and outcomes are better in patients naive to azathioprine (bridging strategy). The data on infliximab as a medical rescue in fulminant colitis are more limited although the efficacy of this anti tumor necrosis factor (TNF) monoclonal antibody has been demonstrated in a controlled trial. Controlled data on the comparative efficacy of cyclosporine and infliximab are not available at this moment. Both drugs are immunosuppressants and are used in combination with steroids and azathioprine, which infers a risk of serious, even fatal, opportunistic infections. Therefore, patients not responding to these agents within 5-7 d should be considered for colectomy and responders should be closely monitored for infections.

Patterns of forest composition and their long term environmental drivers in the tropical dry forest transition zone of southern Africa

Background： Tropical dry forests cover less than 13 % of the world＇s tropical forests and their area and biodiversity are declining. In southern Africa, the major threat is increasing population pressure, while drought caused by climate change is a potential threat in the drier transition zones to shrub land. Monitoring climate change impacts in these transition zones is difficult as there is inadequate information on forest composition to allow disentanglement from other environmental drivers. Methods： This study combined historical and modern forest inventories covering an area of 21,000 km2 in a transition zone in Namibia and Angola to distinguish late succession tree communities, to understand their dependence on site factors, and to detect trends in the forest composition over the last 40 years. Results： The woodlands were dominated by six tree species that represented 84 % of the total basal area and can be referred to as Bdikioea - Pterocarpus woodlands. A boosted regression tree analysis revealed that late succession tree communities are primarily determined by climate and topography. The Schinziophyton rautanenfi and Baikiaea plurijuga communities are common on slightly inclined dune or valley slopes and had the highest basal area （5.5 - 6.2 m^2 ha＆-1）. The Burkea africana - Guibourtia coleosperma and Pterocarpus angolensis - Diafium englerianum communities are typical for the sandy plateaux and have a higher proportion of smaller stems caused by a higher fire frequency. A decrease in overall basal area or a trend of increasing domination by the more drought and cold resilient B. africana community was not confirmed by the historical data, but there were significant decreases in basal area for Ochna pulchra and the valuable fruit tree D. englerianum. Conclusions： The slope communities are more sheltered from fire, frost and drought but are more susceptible to human expansion. The community with the important timber tree P. angolensis can best withstand high fire frequency but shows signs of a higher vulnerability to climate change. Conservation and climate adaptation strategies should include protection of the slope communities through refuges. Follow-up studies are needed on short term dynamics, especially near the edges of the transition zone towards shrub land.

Fixation methods for electron microscopy of human and other liver

For an electron microscopic study of the liver,expertise and complicated,time-consuming processing of hepatic tissues and cells is needed.The interpretation of electron microscopy(EM) images requires knowledge of the liver fine structure and experience with the numerous artifacts in fixation,embedding,sectioning,contrast staining and microscopic imaging.Hence,the aim of this paper is to present a detailed summary of different methods for the preparation of hepatic cells and tissue,for the purpose of preserving long-standing expertise and to encourage new investigators and clinicians to include EM studies of liver cells and tissue in their projects.

The Effect of Exercise Therapy on Physical Function, Biochemistry and Dialysis Adequacy in Haemodialysis Patients: A Systematic Review and Meta-Analysis

Background:Patients undergoing dialysis have high mortality rates and a unique risk factor profile. Some improvements elicited by exercise training have been shown in dialysis populations, here we aimed to further explore the bene-fits of exercise. As well as changes in physical fitness we quantified cardiac function, depression, serum biochemistry, dialysis adequacy and energy intake following exercise training in people with chronic kidney disease (CKD) undertaking dialysis. Methods:A systematic literature search was completed in December 2012 identifying randomized, controlled trials of exercise training studies in haemodialysis (HD) patients. A subsequent meta-analysis was conducted.Results: Twenty four studies were included, totalling 879 patients. Exercise training produced significant improvements in physical fitness: peak VO2 5.03 mlO2·kg-1·min-1 (95% CI 3.73, 6.33, p 0.0001), Knee extensor strength 2.99 kg (95% CI 0.46, 5.52, p = 0.02) and 6 minute walk distance 60.7 metres (95% CI 18.9, 103, p = 0.004). Significant increases in energy intake MD 238 Kcal·day-1 (95% CI 94, 383, p = 0.001), serum Interleukin-6 MD-0.58 pg·ml-1 (95% CI-1.01, -0.15, p = 0.008) and Creactive protein MD 0.92 mg/L-1 (95% CI 0.29, 1.56, p = 0.004), but not Albumin or BMI, were reported. Improved Beck Depression scores were reported MD-6.9 (95% CI-9.7,-4.1, p 0.00001). Dialysis adequacy was reduced MD-0.23 (95% CI -0.29, -0.17, p 0.00001), while serum potassium was higher MD 0.14 mmol·L-1 (95% CI 0.01, 0.27, p = 0.04). Moreover exercise training appeared safe, with no direct exercise-associated deaths in over 30,000 patient-hours. Conclusions: Our pooled analyses confirmed improvements in physical fitness following exercise training and suggested additional improvements in dialysis efficiency (kt/v), serum potassium, inflammation and depression in HD patients.

Everolimus halts hepatic cystogenesis in a rodent model of polycystic-liver-disease

AIM To develop a MRI-based method for accurate determination of liver volume(LV) and to explore the effect of long-term everolimus(EVR) treatment on LV in PCK rats with hepatomegaly. METHODS Thirty-one female PCK rats(model for polycystic-liverdisease: PCLD) were randomized into 3 groups and treatment was started at 16 wk, at the moment of extensive hepatomegaly(comparable to what is done in the human disease). Animals received: controls(n = 14), lanreotide(LAN: 3 mg/kg per 2 wk)(n = 10) or everolimus(EVR: 1 mg/kg per day)(n = 7). LV was measured at week 16, 24, 28. At week 28, all rats were sacrificed and liver tissue was harvested. Fibrosis was evaluated using quantitative image analysis. In addition, gene(quantitative RT-PCR) and protein expression(by Western blot) of the PI3K/Ak T/m TOR signaling pathway was investigated. RESULTS LV determination by MRI correlated excellent with the ex vivo measurements(r = 0.99, P < 0.001). The relative changes in LV at the end of treatment were:(controls) +31.8%;(LAN) +5.1% and(EVR) +8.8%, indicating a significantly halt of LV progression compared with controls(respectively, P = 0.01 and P = 0.04). Furthermore, EVR significantly reduced the amount of liver fibrosis(P = 0.004) thus might also prevent the development of portal hypertension. There was no difference in phosphorylation of Akt(Threonine 308) between LAN-treated PCK rats control PCK rats, whereas S6 was significantly more phosphorylated in the LAN group. Phosphorylation of Akt was not different between controls and EVR treated rats, however, for S6 there was significantly less phosphorylation in the EVR treated rats. Thus, both drugs interact with the PI3K/Ak T/m TOR signaling cascade but acting at different molecular levels.CONCLUSION Everolimus halts cyst growth comparable to lanreotide and reduces the development of fibrosis. m TORinhibition should be further explored in PCLD patients especially those that need immunosuppression.

Separate calculation of DW-MRI in assessing therapeutic effect in liver tumors in rats

AIM:To explore whether the antitumor effect of a vascular disrupting agent(VDA)would be enhanced by combining with an antiangiogenic agent,and whether such synergistic effects can be effectively evaluated with separate calculation of diffusion weighted magnetic resonance imaging(DW-MRI).METHODS:Thirty-seven rats with implanted liver tumors were randomized into the following three groups:(1)ZD6126,a kind of VDA;(2)ZDTHA,ZD6126 in combination with an antiangiogenic,thalidomide;and(3)control.Morphological DW-MRI were performed and quantified before,4 h and 2 d after treatment.The apparent diffusion coefficient(ADC)values were calculated separately for low b values(ADC low),high b values(ADC high)and all b values(ADC all).The tissue perfusion contribution,ADC perf,was calculated as ADC low-ADC high.Imaging findings were finally verified by histopathology.RESULTS:The combination therapy with ZDTHA significantly delayed tumor growth due to synergistic effects by inducing cumulative tumor necrosis.In addition to delaying tumor growth,ZDTHA caused tumor necrosis in an additive manner,which was verified by HE staining.Although both ADC high and ADC all in the ZD6126and ZDTHA groups were significantly higher compared to those in the control group on day 2,the entire tumor ADC high of ZDTHA was even higher than that of ZD6126,but the significant difference was not observed for ADCall between ZDTHA and ZD6126.This indicated that the perfusion insensitive ADC high values calculated from high b value images performed significantly better than ADC all for the monitoring of tumor necrosis on day 2.The perfusion sensitive ADC perf derived from ADC low by excluding high b value effects could better reflect the reduction of blood flow due to the vessel shutdown induced by ZD6126,compared to the ADC low at 4 h.The ADC perf could provide valuable perfusion information from DW-MRI data.CONCLUSION:The separate calculation of ADC is more useful than conventional averaged ADC in evaluating the efficacy of combination therapy with ZD6126and thalidomide for solid tumors.

Heart‘omicsin’AGEing (HOMAGE):design,research objectives and characteristics of the common database

Heart failure is common in older people and its prevalence is increasing.The Heart ＇omics＇ in AGEing（HOMAGE） project aims to provide a biomarker approach that will improve the early diagnosis of heart failure.A large clinical database,based on（1） prospective population studies or（2） cross-sectional,prospective studies or randomized controlled trials（RCTs） of patients at risk for or with overt cardiovascular disease will be constructed to determine most promising ＇omics＇-based biomarkers to identify the risk of developing heart failure and/or comorbidities.Population studies,patient cohorts and RCTs are eligible for inclusion in the common database,if they received ethical approval to obtain and share data and have baseline information on cardiovascular risk factors.Currently,the HOMAGE database includes 43,065 subjects,from 20 studies in eight European countries,including healthy subjects from three population studies in France,Belgium and Italy（n = 7,124）,patients with heart failure（n = 4,312） from four cohorts in the UK,Spain and Switzerland and patients at high risk for cardiovascular disease（n = 31,629） in 13 cohorts.It is anticipated that more partners will join the consortium and enlarge the pooled data.This large merged database will be a useful resource with which to identify candidate biomarkers that play a role in the mechanism underlying the onset and progression of heart failure.