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This is the protocol for a review and there is no abstract. The objectives are as follows: To identify and summarise the evidence from randomised controlled trials assessing the clinical efficacy and safety of resurfacing the patella versus not resurfacing the patella in total knee arthroplasty. The following null hypotheses will be tested: 1.There is no difference in outcome between resurfacing the patella and not resurfacing the patella in patients with osteoarthritis of the knee. 2.There is no difference in outcome between resurfacing the patella and not resurfacing the patella in patients with inflammatory arthritis of the knee. 3.There is no difference in outcome between not resurfacing the patella and resurfacing the patella with different prosthetic designs. 4.There is no difference in outcome between resurfacing the patella and not resurfacing the patella in patients with grade varying grades of patellofemoral arthritis, and varus or valgus deformity of the knee

BACKGROUND: Glioblastoma (GBM) is the most devastating brain tumor. Despite the use of multimodal treatments, most patients relapse, often due to the highly invasive nature of gliomas. However, the detection of glioma infiltration remains challenging. The aim of this study was to assess advanced PET and MRI techniques for visualizing biological activity and infiltration of the tumor. METHODS: Using multimodality imaging, we investigated [(18)F]DPA-714, a radiotracer targeting the 18 kDa translocator protein (TSPO), [(18)F]FET PET, non-Gaussian diffusion MRI (apparent diffusion coefficient, kurtosis), and the S-index, a composite diffusion metric, to detect tumor infiltration in a human invasive glioma model. In vivo imaging findings were confirmed by autoradiography and immunofluorescence. RESULTS: Increased tumor-to-contralateral [(18)F]DPA-714 uptake ratios (1.49 ± 0.11) were found starting 7 weeks after glioma cell implantation. TSPO-PET allowed visualization of glioma infiltration into the contralateral hemisphere 2 weeks earlier compared with the clinically relevant biomarker for biological glioma activity [(18)F]FET. Diffusion-weighted imaging (DWI), in particular kurtosis, was more sensitive than standard T2-weighted MRI to detect differences between the glioma-bearing and the contralateral hemisphere at 5 weeks. Immunofluorescence data reflect in vivo findings. Interestingly, labeling for tumoral and stromal TSPO indicates a predominant expression of TSPO by tumor cells. CONCLUSION: These results suggest that advanced PET and MRI methods, such as [(18)F]DPA-714 and DWI, may be superior to standard imaging methods to visualize glioma growth and infiltration at an early stage.

Research to understand human responses to wildlife and wildlife issues has predominantly focused on cognitions. Yet, as emotions are basic human responses to wildlife, emotions are important too. Integrating cognition and emotion concepts could foster the overall understanding of human-wildlife relationships. This study tested the relationships between valence (the pleasant-unpleasant dimension of emotion) regarding wildlife and wildlife value orientations (patterns of basic cognitions in the context of wildlife). Also, this study estimated the additional predictive potential of emotion next to cognition for the acceptability of lethal control and support for wildlife conservation. Analyses showed that valence was associated with wildlife value orientations. Valence had additional explanatory value next to cognition for conservation support. Valence, however, did not have additional predictive potential for acceptability of lethal control. Based on these findings, we recommend integrating cognition and emotion measurements in future research to understand human responses to wildlife issues. Also, wildlife managers could take the emotion of stakeholders into account in their communication and decision-making processes.

Background: Activation and dysregulation of innate, adaptive and resident immune cells in response to damage determine the pathophysiology of demyelinating disorders. Among the plethora of involved cells, microglia/macrophages and astrocytes play an important role in the pathogenesis of demyelinating disorders. The in-depth investigation of the spatio-temporal profile of these cell types in vivo may inform about the exact disease state and localization as well as may allow to monitor therapeutic modulation of the components of the neuroinflammatory response during the course of multiple sclerosis (MS). In this study, we aimed to non-invasively decipher the degree and temporal profile of neuroinflammation (TSPO - [F-18]DPA-714 PET) in relation to selected magnetic resonance imaging (MRI) parameters (T-2 maps) in the cuprizone (CPZ)-induced model of demyelination. Methods: C57Bl6 (n=30) mice were fed with a standard chow mixed with 0.2% (w/w) CPZ for 4 (n=10; demyelination) and 6 weeks (n=10; spontaneous remyelination). The degree of neuroinflammation at de- and remyelination was assessed by [F-18]DPA-714 PET, multi-echo T-2 MRI, autoradiography and immunohistochemistry. Results: CPZ-induced brain alterations were confirmed by increase of T-2 relaxation times in both white and grey matter after 3 and 5 weeks of CPZ. Peak [F-18]DPA-714 was found in the corpus callosum (CC, white matter), the hippocampus (HC, grey matter) and thalamus (grey matter) after 4 weeks of CPZ treatment and declined after 6 weeks of CPZ. Ex vivo autoradiography and dedicated immunofluorescence showed demyelination/remyelination with corresponding increased/decreased TSPO levels in the CC and hippocampus, confirming the spatial distribution of [F-18]DPA-714 in vivo. The expression of TSPO microglia and astrocytes is time-dependent in this model. Microglia predominantly express TSPO at demyelination, while the majority of astrocytes express TSPO during remyelination. The combination of PET- and MRI-based imaging biomarkers demonstrated the regional and temporal development of the CPZ model-associated neuroinflammatory response in grey and white matter regions. Conclusions: The combination of [F-18]DPA-714 PET and T-2 mapping may allow to further elucidate the regional and temporal profile of inflammatory signals depending on the myelination status, although the underlying inflammatory microenvironment changes. A combination of the described imaging biomarkers may facilitate the development of patient-tailored strategies for immunomodulatory and neuro-restorative therapies in MS.

BACKGROUND: Decompression surgery for lumbar spinal stenosis (LSS) is the most common spinal procedure in the elderly. To avoid persisting low back pain, adding arthrodesis has been recommended, especially if there is a coexisting degenerative spondylolisthesis. However, this strategy remains controversial, resulting in practice-based variation.PURPOSE: To evaluate in a pragmatic study if surgical selection criteria and variation in use of arthrodesis in three Scandinavian countries can be linked to variation in treatment effectiveness.STUDY DESIGN: An observational study based on a combined cohort from the national spine registries of Norway, Sweden, and Denmark.PATIENT SAMPLE: Patients aged 50 and higher operated 2011-2013 for LSS were included.OUTCOME MEASURES: Patient-reported outcome measures (PROMs) Oswestry disability index (ODI) (primary outcome), numeric rating scale (NRS) for leg pain and back pain, and health-related quality of life (EQ-5D). Analysis included case-mix adjustment. In addition, we report differences in hospital stay.METHODS: Analyses of baseline data were done by analysis of variance (ANOVA), Chi-square, or logistic regression tests. The comparisons of the mean changes of PROMs at one-year follow-up between the countries were done by ANOVA (crude) and analyses of covariance (ANCOVA, case mix adjustment). There are no conflicts of interest. Funding was received from the Danish Society of Spinal Surgery ($5,925), the Northern Norway Regional Health Authority ($5,925) and from Swedish Association of Local Authorities and Regions ($11,885). The sponsor had no role in the acquisition of data, analysis, or preparation of the manuscript.RESULTS: Out of 14,223 included patients, 10,890 (77%) responded at one-year follow-up. Apart from fewer smokers in Sweden and higher comorbidity rate in Norway, baseline characteristics were similar. The rate of additional fusion surgery (patients without, with spondylolisthesis) was: Norway 11% (4%, 47%), Sweden 21% (9%, 56%) and Denmark 28% (15%, 88%). At one-year follow-up the mean improvement for ODI (95%CI) was: Norway 18 (17 to 18), Sweden 17 (17 to 18), and Denmark 18 (17 to 19). Patients operated with arthrodesis had prolonged hospital stay.CONCLUSIONS: Real life data from three national spine registers showed similar indications for decompression surgery, but significant differences in the use of concomitant arthrodesis in Scandinavia. Additional arthrodesis was not associated with better treatment effectiveness.

Trypanosomes are important disease agents of humans, livestock and cold-blooded species, including fish. The cellular morphology of trypanosomes is central to their motility, adaptation to the host’s environments and pathogenesis. However, visualizing the behaviour of trypanosomes resident in a live vertebrate host has remained unexplored. In this study, we describe an infection model of zebrafish (Danio rerio) with Trypanosoma carassii. By combining high spatio-temporal resolution microscopy with the transparency of live zebrafish, we describe in detail the swimming behaviour of trypanosomes in blood and tissues of a vertebrate host. Besides the conventional tumbling and directional swimming, T. carassii can change direction through a ‘whip-like’ motion or by swimming backward. Further, the posterior end can act as an anchoring site in vivo. To our knowledge, this is the first report of a vertebrate infection model that allows detailed imaging of trypanosome swimming behaviour in vivo in a natural host environment., eLife digest Trypanosomes are one-celled parasites that cause the disease trypanosomiasis, which is also known as sleeping sickness. Trypanosomiasis is transmitted to humans and animals by a type of fly, known as tse-tse, which is commonly found in sub-Saharan Africa. A bite from the tse-tse fly transfers the trypanosome cells into the host’s bloodstream, where they spread from the blood to the internal organs and brain. This leads to a long-term illness, which can sometimes result in a coma and eventually death. Once in the blood trypanosomes move around using a structure similar to an underwater propeller called the flagellum. How the trypanosomes move and behave in the blood determines how the infection will progress. Until now it has only been possible to observe trypanosomes in plastic dishes or in blood drawn from infected patients. However, neither of these settings mimic the conditions of the bloodstream, and it is currently impossible to look inside human hosts to watch how trypanosomes move. To overcome this hurdle, Doro et al. infected zebrafish with Trypanosoma carassii, a close relative of the sub-Saharan trypanosomes that specifically infects fish. Zebrafish are transparent when young, making it possible to observe the parasite in the blood and tissues of live fish using a microscope. Doro et al. noticed that Trypanosoma carassii cells adapt to different environments in the host by using different swimming techniques. For example, in small capillaries trypanosomes were dragged along with the blood flow, whilst in larger vessels, when blood flow was slow or there were fewer red blood cells, trypanosomes actively swam against the current. The parasites were also able to change direction by using their flagella in a ‘whip-like’ motion. Lastly, it was discovered that Trypanosoma carassii could rapidly attach to blood vessel walls using one end of its cell body, even when blood flow was strong. This behaviour may help the parasites escape from the bloodstream into the surrounding tissues, making the infection more dangerous. Studying how trypanosomes infect zebrafish at this high level of detail provides new insights into how these parasites move and behave inside a host. An important question that remains to be answered, is how exactly the trypanosomes leave the bloodstream. A better understanding of the whole infection process may hint at new ways of fighting these deadly infections in future.

Purpose: Yearly incidence of surgery for symptomatic lumbar disc herniation varies and is 29/100,000 in Sweden, 46/100,000 in Denmark and 58/100,000 in Norway. This variation was used to study whether differences in surgical incidence were associated with differences in preoperative patient characteristics as well as patient-reported outcomes. Methods: Data from the national spine registers in Sweden, Denmark and Norway during 2011–2013 were pooled, and 9965 individuals, aged 18–65 years, of which 6468 had one-year follow-up data, were included in the study. Both absolute and case-mix-adjusted comparisons of the primary outcome Oswestry Disability Index (ODI) and the secondary outcomes EQ-5D-3L, and Numerical Rating Scale (NRS) for leg and back pain were performed. Case-mix adjustment was done for baseline age, sex, BMI, smoking, co-morbidity, duration of leg pain and preoperative value of the dependent variable. Results: Mean improvement in the outcome variables exceeded previously described minimal clinical important change in all countries. Mean (95% CI) final scores of ODI were 18 (17–18), 19 (18–20) and 15 (15–16) in Sweden, Denmark and Norway, respectively. Corresponding results of EQ-5D-3L were 0.74 (0.73–0.75), 0.73 (0.72–0.75) and 0.75 (0.74–0.76). Results of NRS leg and back pain behaved similarly. Case-mix adjustment did not alter the findings substantially. Conclusion: We found no clear association between incidence of surgery for lumbar disc herniation and preoperative patient characteristics as well as outcome, and the differences between the countries were lower than the minimal clinical important difference in all outcomes. Graphical abstract: These slides can be retrieved under Electronic Supplementary Material.[Figure not available: see fulltext.].

Routine diagnostic screening of inborn errors of metabolism (IEM) is currently performed by different targeted analyses of known biomarkers. This approach is time-consuming, targets a limited number of biomarkers and will not identify new biomarkers. Untargeted metabolomics generates a global metabolic phenotype and has the potential to overcome these issues. We describe a novel, single platform, untargeted metabolomics method for screening IEM, combining semi-automatic sample preparation with pentafluorophenylpropyl phase (PFPP)-based UHPLC- Orbitrap-MS. We evaluated analytical performance and diagnostic capability of the method by analysing plasma samples of 260 controls and 53 patients with 33 distinct IEM. Analytical reproducibility was excellent, with peak area variation coefficients below 20% for the majority of the metabolites. We illustrate that PFPP-based chromatography enhances identification of isomeric compounds. Ranked z-score plots of metabolites annotated in IEM samples were reviewed by two laboratory specialists experienced in biochemical genetics, resulting in the correct diagnosis in 90% of cases. Thus, our untargeted metabolomics platform is robust and differentiates metabolite patterns of different IEMs from those of controls. We envision that the current approach to diagnose IEM, using numerous tests, will eventually be replaced by untargeted metabolomics methods, which also have the potential to discover novel biomarkers and assist in interpretation of genetic data.

Sciatica due to lumbar disc herniation refractory to conservative treatment is effectively treated by surgery. The primary goal of surgery is retrieval of herniated disc fragments and decompression of the nerve root. After the historical publication of Mixter and Barr [1], who performed extensive laminectomy with transdural excision of the herniated disc, lumbar disc surgery became one of the most frequently performed surgical procedures worldwide. With the introduction of the microscope in the late 1960s, Yasargil and Caspar launched the unilateral microdiscectomy [2]. Presently, unilateral transflaval microdiscectomy by using the microscope or headlight with loupe magnification, is regarded as the golden standard. However, a shift towards minimally invasive approaches to the spine has started. The rationale behind minimally invasive spine surgery is less tissue damage, shorter hospitalisation, and faster recovery while achieving a good clinical outcome comparable with that of open conventional surgery. Minimally invasive spine surgery has adopted several techniques from other fields and has been influenced by endoscopy, biochemical advances, lasers, and image guidance systems. Intradiscal chymopapaine has been used more than 30 years but has been abandoned since it is less effective than surgical nerve root decompression [3]. Hijikata and Kambin are credited for their first report of percutaneous nucleotomy by inserting a 7 mm diameter tube under local anaesthesia with partial resection of disc material [4]. Choi and Ascher reviewed the first results of percutaneous laser disc decompression aiming at decreasing intradiscal pressure and subsequent nerve root relief [5]. The concept of posterolateral endoscopic discectomy changed from central nucleotomy to transforaminal nerve root decompression, which was launched by Hoogland [6] A few years later, Foley and Smith introduced the transmuscular approach of microendoscopic tubular discectomy with advanced optics and instruments applicated in laparoscopic surgery [7], which was later modified with the operative microscope.

We present a 86-year-old patient who suffered from progressive weakness in his right leg. Due to a hypercholesterinemia he had received Simvastatin for a few years. Because of higher cholesterine levels the dosis had been increased from 40 to 80 mg 6 months ago.We saw elevated levels of creatinine kinase and creatinine. In the EMG, a neuromuscular impairment was detected. In context with the medical history we could make the diagnosis of a statin-induced myopathy with rhabdomyolysis.After stopping the medication with statin and under liquid substitution, creatinine kinase and creatinine levels dropped. After therapy the weakness of the leg was totally recurrent.In case of unclear neurological symptoms and under therapy with statins, a myopathy should be considered.Wir berichten von einem 86-jährigen Patienten, der aufgrund einer zunehmenden Schwäche des rechten Beines aufgenommen wurde.Laborchemisch zeigten sich erhöhte Blutspiegel von Kreatinkinase und Kreatinin und im EMG konnte zusätzlich eine pseudomonotone Entladung im Sinne einer neuromuskulären Schädigung nachgewiesen werden. Da anamnestisch eine Erhöhung der Statindosis auf 80 mg täglich vor ca. 6 Monaten zu eruieren war, wurde die Diagnose einer Simvastatin-induzierten Myopathie mit Rhabdomyolyse gestellt.Nach Absetzen der Statin-Therapie und unter Flüssigkeitssubstitution zeigten sich sowohl die Laborwerte als auch die klinische Symptomatik deutlich rückläufig.Bei unklarer neurologischer Symptomatik unter Statin-Therapie sollte an eine Statin-induzierte Myopathie gedacht und ggf. die Therapie beendet werden.

Analyzing digital images is an important investigation in forensics with the ever increasing number of images from computers and smartphones. In this article we aim to advance the state-of-the-art in common image source identification (which images originate from the same source camera). To this end, we present two types of applications for different goals that make use of a) a modern Desktop computer with a GPU and b) highly heterogeneous cluster computers with many different kinds of GPUs, something we call computing jungles. The first application targets medium-scale investigations, for example within a crime laboratory, the second application is targeted at large-scale investigations, for example within institutions. We advance the state-of-the-art by 1) explaining in detail how we obtain the performance to 2) support large databases of images in reasonable time while 3) not giving up accuracy. Moreover, we do not apply filtering ensuring that 4) our results are highly reproducible.

This article addresses the applicability of quantitative wildlife value orientation scales in Muslim students in Malaysia. As Malaysian culture is deeply influenced by Islam ideology, this article presents a case for addressing the cross-cultural applicability of the scales. The current wildlife value orientation scales were reliable—all Cronbach’s alphas ≥ .65—and had predictive validity—8 to 14% of variance of acceptability of lethal control was explained. Yet, both reliability and predictive validity were of lesser magnitude than figures in previous Western studies. Especially the hunting beliefs scale did not reflect basic thinking about wildlife in our sample, and our data suggest two different hunting dimensions—consequences of hunting for wildlife and human opportunities for hunting. For future cross-cultural comparisons of wildlife value orientations, amendment of the scales to better reflect salient beliefs in non-Western nations is recommended.

BackgroundRecent meta-analyses of resting-state networks in major depressive disorder (MDD) implicate network disruptions underlying cognitive and affective features of illness. Heterogeneity of findings to date may stem from the relative lack of data parsing clinical features of MDD such as phase of illness and the burden of multiple episodes.MethodResting-state functional magnetic resonance imaging data were collected from 17 active MDD and 34 remitted MDD patients, and 26 healthy controls (HCs) across two sites. Participants were medication-free and further subdivided into those with single v. multiple episodes to examine disease burden. Seed-based connectivity using the posterior cingulate cortex (PCC) seed to probe the default mode network as well as the amygdala and subgenual anterior cingulate cortex (sgACC) seeds to probe the salience network (SN) were conducted.ResultsYoung adults with remitted MDD demonstrated hyperconnectivity of the left PCC to the left inferior frontal gyrus and of the left sgACC to the right ventromedial prefrontal cortex (PFC) and left hippocampus compared with HCs. Episode-independent effects were observed between the left PCC and the right dorsolateral PFC, as well as between the left amygdala and right insula and caudate, whereas the burden of multiple episodes was associated with hypoconnectivity of the left PCC to multiple cognitive control regions as well as hypoconnectivity of the amygdala to large portions of the SN.ConclusionsThis is the first study of a homogeneous sample of unmedicated young adults with a history of adolescent-onset MDD illustrating brain-based episodic features of illness.

OBJECT Delayed ischemic neurological deficits (DINDs) and cerebral vasospasm (CVS) are responsible fora poor outcome in patients with aneurysmal subarachnoid hemorrhage (SAH), most likely because of a decreased availability of nitric oxide (NO) in the cerebral microcirculation. In this study, the authors examined the effects of treatment with the NO donor molsidomine with regard to decreasing the incidence of spasm-related delayed brain infarctions and improving clinical outcome in patients with SAH. METHODS Seventy-four patients with spontaneous aneurysmal SAH were included in this post hoc analysis. Twenty-nine patients with SAH and proven CVS received molsidomine in addition to oral or intravenous nimodipine. Control groups consisted of 25 SAH patients with proven vasospasm and 20 SAH patients without. These patients received nimodipine therapy alone. Cranial computed tomography (CCT) before and after treatment was analyzed for CVS-related infarcts. A modified National Institutes of Health Stroke Scale (mNIHSS) and the modified Rankin Scale (mRS) were used to assess outcomes at a 3-month clinical follow-up. RESULTS Four of the 29 (13.8%) patients receiving molsidomine plus nimodipine and 22 of the 45 (48%) patients receiving nimodipine therapy alone developed vasospasm-associated brain infarcts (p < 0.01). Follow-up revealed a median mNIHSS score of 3.0 and a median mRS score of 2.5 in the molsidomine group compared with scores of 11.5 and 5.0, respectively, in the nimodipine group with CVS (p < 0.001). One patient in the molsidomine treatment group died, and 12 patients in the standard care group died (p < 0.01). CONCLUSIONS In this post hoc analysis, patients with CVS who were treated with intravenous molsidomine had a significant improvement in clinical outcome and less cerebral infarction. Molsidomine offers a promising therapeutic option in patients with severe SAH and CVS and should be assessed in a prospective study.

Efficient freight movement is inextricably linked to the economic vitality of a local area, the state, and beyond. In light of performance-based programs at the national level, there is increased interest in freight performance monitoring and methods for gaining a better understanding of the freight system for investment decisions. Public agencies in the State of Maryland are leaders in investigating freight traffic and trends for improved public investment. Implementing freight fluidity is a natural next step to understanding better the state’s freight investment needs. This paper describes the freight fluidity concept and how this concept will be implemented in Maryland. The paper documents work sponsored by the Maryland Department of Transportation State Highway Administration and performed by the Texas A&M Transportation Institute through the University of Maryland Center for Advanced Transportation Technology. This paper presents a definition of freight fluidity for the State of Maryland, provides a framework for implementing freight fluidity, describes multimodal data sources, and presents calculation procedures for the highway (truck mode). The application described here was successful in demonstrating freight fluidity use in Maryland. Researchers demonstrated the value of the freight fluidity methods for freight investments and decision making in Maryland. Given increased interest in implementing freight fluidity in the United States, the framework and methods described here would be valuable to transportation professionals investigating ways to implement freight fluidity in their local area, state, or region, or even globally.

Objective To evaluate the ability of sperm DNA fragmentation index (DFI%) and high DNA stainability (HDS%) to influence the chance of achieving pregnancy in couples undergoing intracytoplasmic sperm injection (ICSI) cycles. Design A retrospective study evaluating couples that underwent an ICSI cycle between 2009 - 2018 Setting High-volume reproductive center. Patients Consecutive couples who underwent an ICSI cycle and had a semen analysis with subsequent DFI% and HDS% testing, evaluated by Sperm Chromatin Structure Assay (SCSA). Interventions Measurement of DFI% and HDS% prior to ICSI cycle. Main Outcome Measures To determine whether DFI% or HDS% of sperm was predictive of the number of ICSI cycles until the first clinical intrauterine pregnancy. Results A total of 550 couples who underwent 1050 ICSI cycles were analyzed. Of those, a total of 330 couples achieved pregnancy. As expected, in couples that achieved pregnancy, females were younger (33.7 ± 3.6 years vs 35.3 ± 3.4 years; p Conclusions Neither DFI nor HDS at baseline influence the chances of a couple to achieve pregnancy after ICSI. Increased female age and couples who underwent more ICSI cycles were associated with lower chances of achieving pregnancy.

Early-onset depression is associated with increased lifespan chronicity, suicidality, and the functional burdens associated with recurrent episodes. Reduction of these negative long-term outcomes requires an understanding of what interventions reduce vulnerabilities or ameliorate their associated neural patterns. Rumination-Focused Cognitive Behavior Therapy (RFCBT), an evidence-based treatment which directly targets a well-known risk for depressive relapse (i.e., ruminative habit), has shown preliminary success for reducing relapse rates among adolescents and adults in remission from Major Depressive Disorder (rMDD). In the current pilot study, clinical outcomes and neuroimaging predictors are explored over two years following a randomized controlled trial of eight weeks of RFCBT (n = 17) or Assessment Only (AO; n = 16) to prevent depressive relapse among adolescents. Baseline neural activation during a rumination induction task, neural change during treatment, and treatment group are examined as predictors of relapse. Regions selected were based upon hyperactivation patterns in rMDD compared to healthy adolescents, and occurred largely in default mode, somatomotor, visual and salience network regions. Twenty-five adolescents successfully completed quality fMRI scans at Baseline and after eight weeks of RFCBT or AO. RFCBT-treated youth maintained lower depression scores over the two-year period, relapsed at slower and less frequent rates, and were hospitalized less often for suicidality than AO. Although both groups reported lower ruminative tendencies after one year, at two-year follow-up, RFCBT maintained reductions whereas AO reported a return of ruminative tendencies. Adolescents who demonstrated higher activation at Baseline in default mode and limbic regions during rumination induction reported reduced depressive symptoms over the follow-up period. These data offer preliminary evidence that targeting rumination can stave off depressive relapse among vulnerable adolescents, and that such targeted treatment may aid a compensation process for disease-related brain functioning reducing risk to further depressive episodes. Clinical trials registration NCT01905267, https://clinicaltrials.gov/ct2/show/NCT01905267

Only small amounts of data are available on the prescription frequency of physical therapies (PT) for patients with rheumatoid arthritis (RA).The aim of the study was to evaluate prescription frequencies of PT considering functional status and sociodemographic factors.A total of 98,963 adults diagnosed with RA in 2013 were identified in claims data from the BARMER health insurance. A questionnaire was sent to a representative sample of 6193 people requesting information on the disease status. Of these 2535 persons were included who agreed to the linking of the questionnaire and claims data and who confirmed a diagnosis of RA. From the routine claims data the prescription of PT and occupational therapy as well as the medical discipline of the prescribing physician were analyzed. Multivariable logistic regression was conducted to determine which variables (age, sex, M05/M06 diagnosis, residential area, income, functional status and rheumatological care) were associated with the use of PT.In 2015 a total of 47% of the study population received PT (35% physiotherapy, 15% thermotherapy, 15% manual therapy, 2% electrotherapy and 6% massage) and 3% occupational therapy. Of the PT prescriptions 37% were issued by general practitioners, 27% by orthopedists and 18% by rheumatologists. Women and persons living in the eastern states of Germany and patients with high functional impairment were prescribed PT more often. Income, educational status, seropositivity and rheumatological care did not have any influence on the frequency of prescription of PT.There are deficits in the outpatient prescription of PT but without indications of an undersupply of population groups due to low socioeconomic status. In contrast to the prescription of disease-modifying antirheumatic drug (DMARD) treatment, PT is predominantly prescribed by general practitioners.

What concentration of anti-Müllerian hormone (AMH) corresponds to an antral follicle count (AFC)15 for determination of ovarian reserve?A prospective study conducted at 13 US fertility clinics in women aged 21-44 years who presented for AFC evaluation by transvaginal ultrasound. Serum samples were collected at the time of AFC evaluation (menstrual cycle day 2-4). AMH concentrations were measured by the ElecsysIn the derivation cohort (n = 306), an optimal serum AMH cut-off value of 1.77 ng/ml was determined to correspond to AFC15 with 89.63% sensitivity and 69.01% specificity, using the Elecsys AMH assay. In the validation cohort (n = 856), this 1.77 ng/ml cut-off could identify women with an AFC15 with a sensitivity of 88.34% and a specificity of 68.29%; corresponding positive predictive and negative predictive values were 75.19% and 84.34%, respectively. ROC analyses demonstrated that AMH performed better than oestradiol or FSH in predicting AFC, with area under the curves of 85.7%, 57.1% and 69.7%, respectively, in the validation cohort.The Elecsys AMH immunoassay provides a robust and fully automated method to measure serum AMH levels. Women with AMH values below the cut-off of 1.77 ng/ml are unlikely to have AFC15.

Background Few studies have assessed the safety and effectiveness of the numerous available chemotherapeutic therapies for geriatric oncology patients. Most safety studies are conducted in large trials, and there is some uncertainty surrounding whether the results would be the same in typical daily use. Objective This retrospective study aims to assess the adverse effects of real-world capecitabine use in elderly patients. Methods We reviewed the records of patients treated with capecitabine in an oncology department of a University Clinic in Nijmegen, The Netherlands. We scored adverse effects such as hand-foot syndrome and diarrhea, and dosage adjustments and the reasons for them. In total, 132 patients were included, 69 of whom were aged 70 years or below (mean age: 57 years), while 63 were aged older than 70 years (mean age: 74 years). Results Patients aged over 70 years experienced more serious adverse effects than younger patients. Grade 2 or 3 hand-foot syndrome toxicity was experienced by 20.2% of patients aged younger than 70 years and by 34.9% of patients older than 70 years (p = 0.059). Grade 2, 3, or 4 diarrhea was experienced by 17.4% of the patients aged younger than 70 years but by 31.7% of the patients aged older than 70 years (p = 0.044). Dosage was adjusted for 27/69 patients in the younger group and 52/63 patients in the older group (p = 0.001). Conclusion The difference in observed adverse effects cannot be the sole explanation for the high incidence of observed dose adjustments. A prospective follow-up study of elderly patients using capecitabine outside clinical trials is needed to evaluate the optimum balance between adverse effects and efficacy.

There is substantial variability across studies of default mode network (DMN) connectivity in major depressive disorder, and reliability and time-invariance are not reported. This study evaluates whether DMN dysconnectivity in remitted depression (rMDD) is reliable over time and symptom-independent, and explores convergent relationships with cognitive features of depression. A longitudinal study was conducted with 82 young adults free of psychotropic medications (47 rMDD, 35 healthy controls) who completed clinical structured interviews, neuropsychological assessments, and 2 resting-state fMRI scans across 2 study sites. Functional connectivity analyses from bilateral posterior cingulate and anterior hippocampal formation seeds in DMN were conducted at both time points within a repeated-measures analysis of variance to compare groups and evaluate reliability of group-level connectivity findings. Eleven hyper- (from posterior cingulate) and 6 hypo- (from hippocampal formation) connectivity clusters in rMDD were obtained with moderate to adequate reliability in all but one cluster (ICC's range = 0.50 to 0.76 for 16 of 17). The significant clusters were reduced with a principle component analysis (5 components obtained) to explore these connectivity components, and were then correlated with cognitive features (rumination, cognitive control, learning and memory, and explicit emotion identification). At the exploratory level, for convergent validity, components consisting of posterior cingulate with cognitive control network hyperconnectivity in rMDD were related to cognitive control (inverse) and rumination (positive). Components consisting of anterior hippocampal formation with social emotional network and DMN hypoconnectivity were related to memory (inverse) and happy emotion identification (positive). Thus, time-invariant DMN connectivity differences exist early in the lifespan course of depression and are reliable. The nuanced results suggest a ventral within-network hypoconnectivity associated with poor memory and a dorsal cross-network hyperconnectivity linked to poorer cognitive control and elevated rumination. Study of early course remitted depression with attention to reliability and symptom independence could lead to more readily translatable clinical assessment tools for biomarkers.

Background Fibromyalgia (FM) is characterised by chronic widespread pain and other symptoms such as fatigue, sleep disturbances and cognitive problems. Psychosocial factors and personality traits may be present in a variable degree and may play a role in the perception, coping and treatment of FM. Objectives We looked for symptoms of hyperventilation, depression, anxiety and burn-out as well as for personality traits such as hypersensitivity and alexithymia in a large sample of patients. We looked at differences in prevalence of these symptoms in the population when selected by the 1990 FM classification criteria and by the 2010 diagnostic FM criteria. Methods A large group of patients presenting on the Unit of Physical Medicine between 2014 and 2017 with chronic widespread pain was analysed and grouped depending on the 1990 ACR classification criteria for FM on one hand and the 2010 ACR diagnostic criteria for FM on the other hand. Self-administered tools used were the Nijmegen questionnaire (hyperventilation), the Aron questionnaire (hypersensitivity), the HADS questionnaire (anxiety and depression), the BMS-10 questionnaire (burn-out) and the TAS alexithymia questionnaire. Results Out of 1085 patients, 828 (76%) fulfilled the 1990 ACR classification criteria for FM. Hyperventilation (score ≥12) was found in 97% and hypersensitivity (score ≥12) in 75%. Symptoms of anxiety and depression (scores≥11) were observed in 59% and 36% respectively. Burn-out (score ≥4.5) was seen in 40% of patients while a high TAS score (≥8) was found in 70% of patients. Overall, 906 patients fulfilled the 2010 ACR diagnostic criteria for FM. The distributions of disease characteristics and personality traits in this population were very similar. Only 38 out of these 906 patients had a wide spread pain index (WPI) of 3 to 6. Conclusions A significant number of patients demonstrated high levels of anxiety, more than depression. Hypersensitivity and alexithymia were also found to be highly prevalent. There was a substantial level of hyperventilation. It may be useful to consider all these characteristics in the development of treatment programs for FM patients. Results were similar when groups were selected by 1990 ACR classification criteria for FM or by the 2010 ACR diagnostic criteria for FM. Only a minority of patients had a WPI of 3 to 6. References [1] Van Dixhoorn J, et al. 1985. [2] Wolfe, et al. 1990. [3] Aron, et al. 1997. [4] Maslach, et al. 1996. [5] Wolfe, et al. 2010. [6] Maes, et al. 2014. Disclosure of Interest None declared

For the selection of treatment in patients with spinal bone metastases (SBM), survival estimation plays a crucial role to avoid over- and under-treatment. To aid clinicians in this difficult task, several prediction models have been developed, consisting of many different risk factors. The aim of this systematic review was to identify prognostic factors that are associated with survival in patients with SBM to support development of predictive models. A systematic review was performed with focus on prognostic factors associated with survival in patients with SBM. Two reviewers independently selected studies for inclusion and assessed the risk of bias. A level of evidence synthesis was performed for each prognostic factor. Inter-observer agreement for the risk of bias assessment was determined by the kappa-statistic. After screening, 142 full-text articles were obtained, of which 22 met the eligibility criteria. A total of 43 different prognostic factors were investigated in the included studies, of which 17 were relevant to pre-treatment survival estimation. The prognostic factors most frequently associated with survival were the primary tumor and the performance status. The prognostic factors most frequently not associated with survival were age, gender, number and location of the SBM and the presence of a pathologic fracture. Prognostication for patients with SBM should be based on an accurate primary tumor classification, combined with a performance score. The benefit of adding other prognostic factors is doubtful.

Background The placement of intervertebral cages in anterior cervical discectomy (ACDF) supposedly maintains foraminal height. The most commonly reported cage-related complication is subsidence, although it is unknown whether a correlation between subsidence and clinical outcome exists. Aim To assess the incidence and relevance of subsidence. Methods Literature searches were performed in PubMed, MEDLINE, Embase, Web of Science, COCHRANE, and CENTRAL. The inclusion criteria were as follows: ≥ 20 patients, ADCF with cage, subsidence assessed, and primary data. Risk of bias was assessed using adjusted Cochrane checklists. Results Seventy-one studies, comprising 4784 patients, were included. Subsidence was generally defined as ≥ 3-mm loss of height comparing postoperative intervertebral heights with heights at last follow-up. Mean incidence of subsidence was 21% (range 0–83%). Of all patients, 46% of patients received polyether-ether-ketone (PEEK) cages, 31% received titanium cages, 18% received cage-screw-combinations, and 5% received polymethyl-methacrylate (PMMA) cages. Patients treated with cage-screw-combinations had significantly less subsidence than patients treated with PEEK, titanium, or PMMA cages (15.1% vs. 23.5% vs. 24.9% vs. 30.2%; p

Background Three well-established intrinsic connectivity networks (ICNs) involved in cognitive-affective processing include the cognitive control network (CCN), default mode network (DMN), and salience and emotional network (SEN). Despite recent advances in understanding developmental changes in these ICNs, the majority of research has focused on single seeds or networks in isolation with limited age ranges. Additionally, although internalizing psychopathologies (IPs), such as anxiety and depression, are often characterized by maladaptive cognitive-affective processing styles, it is not clear how IP history influences age-related changes in brain networks. Method The current study aimed to characterize the normative development of the CCN, DMN, and SEN across a large age-span (7-29 year olds) of typically developing (TD) individuals (n = 97). We also explore how age may impact differences in network connectivity between TD individuals and patients with IPs (n = 136). Results Among TD individuals, DMN and CCN connectivity strengthened with age, whereas connectivity between the SEN and ventromedial prefrontal cortex weakened across development. When exploring group (IP vs. TD) differences, the IP group was characterized by greater connectivity between the CCN and cerebellum and between the SEN and caudate from childhood to early adulthood, relative to TD individuals. In addition, patients with IPs, versus TD individuals, exhibited reduced connectivity between the SEN and medial frontal gyrus from adolescence to adulthood. Conclusions The current findings shed light on differential age-related changes in brain network patterns among psychiatrically free, TD individuals and those with internalizing disorders, and may provide plausible targets for novel mechanism-based treatments that differ based on developmental stage.

Using displays in which a moving disk disappeared behind an occluder, we examined whether an accompanying auditory rhythm influenced the perceived displacement of the disk during occlusion. We manipulated a baseline rhythm, comprising a relatively fast alternation of equal sound and pause durations. We had two different manipulations to create auditory sequences with a slower rhythm: either the pause durations or the sound durations were increased. In the trial, a disk moved at a constant speed, and at a certain point moved behind an occluder during which an auditory rhythm was played. Participants were instructed to track the occluded disk, and judge the expected position of the disk at the moment that the auditory rhythm ended by touching the judged position on a touch screen. We investigated the influence of the auditory rhythm, i.e., ratio of sound to pause duration, and the influence of auditory density, i.e., the number of sound onsets per time unit, on the judged distance. The results showed that the temporal characteristics affected the spatial judgments. Overall, we found that in the current paradigm relatively slow rhythms led to shorter judged distance as compared to relatively fast rhythms for both pause and sound variations. There was no main effect of auditory density on the judged distance of an expected visual event. That is, whereas the speed of the auditory rhythm appears crucial, the number of sound onsets per time unit as such, i.e., the auditory density, appears a much weaker factor.

著者人数: 70名(所属. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS): 芝井, 広; 船木, 一幸; 磯部, 直樹; 川田, 光伸; 權, 靜美; 松原, 英雄; 中川, 貴雄; 小川, 博之; 佐藤, 洋一; 篠崎, 慶亮; 杉田, 寛之; 和田, 武彦; 山田, 亨; 山村, 一誠), Number of authors: 70(Affiliation. Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency (JAXA)(ISAS): Shibai, Hiroshi; Funaki, Ikkoh; Isobe, Naoki; Kawada, Mitsunobu; Kwon, Jungmi; Matsuhara, Hideo; Nakagawa, Takao; Ogawa, Hiroyuki; Sato, Yoichi; Shinozaki, Keisuke; Sugita, Hiroyuki; Wada, Takehiko; Yamada, Toru; Yamamura, Issei), 資料番号: SA1180106000

This chapter briefly discusses a descriptive typology of attitudes towards wildlife that was quite influential in the pioneering years of research on human dimensions of wildlife. It describes a more recent theory‐driven approach to understanding human relationships with wildlife, guided by the cognitive hierarchy. The theory of cognitive hierarchy stresses that individual behaviour is guided by a hierarchy of interrelated cognitions including values, value orientations, attitudes and norms, and behavioural intentions. Studies using the wildlife value orientation scales suggest that domination orientations are deeply engrained in the cultural transmission process and endure over generations. The usefulness of studying wildlife value orientations depends on the concept's predictive validity. The cognitive hierarchy does not explicitly consider emotions. The concepts and measurements may reflect emotional content, but they are not intended to directly capture emotional dispositions or responses. Future research on human dimensions of wildlife may benefit from the study of both cognitive and emotional responses to wildlife. Environmental Psychology Environmental Psychology: An Introduction, Second Edition

PURPOSE: We recently reported that high thymidine phosphorylase (TP) expression is accompanied by low tumor thymidine concentration and high 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) uptake in four untreated lung cancer xenografts. Here, we investigated whether this relationship also holds true for a broader range of tumor models. PROCEDURES: Lysates from n = 15 different tumor models originating from n = 6 institutions were tested for TP and thymidylate synthase (TS) expression using western blots. Results were correlated to [(18)F]FLT accumulation in the tumors as determined by positron emission tomography (PET) measurements in the different institutions and to previously published thymidine concentrations. RESULTS: Expression of TP correlated positively with [(18)F]FLT SUVmax (ρ = 0.549, P

We extend the Datalog engine VLog to develop a column-oriented implementation of the skolem and the restricted chase – two variants of a sound and complete algorithm used for model construction over theories of existential rules. We conduct an extensive evaluation over several data-intensive theories with millions of facts and thousands of rules, and show that VLog can compete with the state of the art, regarding runtime, scalability, and memory efficiency.

Neurofeedback has been used to treat a variety of problems and symptoms related to central nervous system dysregulation, including chronic pain conditions. However, there is limited published work describing the application and efficacy of neurofeedback for chronic pain. This case series describes the outcomes of neurofeedback treatment of four patients with diverse diagnoses and pain symptoms. Although there was variability in patient response, all patients reported improvements in pain and other symptoms with treatment. The findings indicate that more research to (1) clarify the benefits of neurofeedback for different conditions and (2) identify the most effective protocols for individual patients is warranted.

Aim Impairment in neuropsychological functioning is common in major depressive disorder (MDD), but it is not clear to what degree these deficits are related to risk (e.g. trait), scar, burden or state effects of MDD. The objective of this study was to use neuropsychological measures, with factor scores in verbal fluency, processing speed, attention, set-shifting and cognitive control in a unique population of young, remitted, unmedicated, early course individuals with a history of MDD in hopes of identifying putative trait markers of MDD. Methods Youth aged 18–23 in remission from MDD (rMDD; n = 62) and healthy controls (HC; n = 43) were assessed with neuropsychological tests at two time points. These were from four domains of executive functioning, consistent with previous literature as impaired in MDD: verbal fluency and processing speed, conceptual reasoning and set-shifting, processing speed with interference resolution, and cognitive control. Results rMDD youth performed comparably to HCs on verbal fluency and processing speed, processing speed with interference resolution, and conceptual reasoning and set-shifting, reliably over time. Individuals with rMDD demonstrated relative decrements in cognitive control at Time 1, with greater stability than HC participants. Conclusion MDD may be characterized by regulatory difficulties that do not pertain specifically to active mood state or fluctuations in symptoms. Deficient cognitive control may represent a trait vulnerability or early course scar of MDD that may prove a viable target for secondary prevention or early remediation.

Stroke is the most common cause of death and disability from neurologic disease in humans. Activation of microglia and matrix metalloproteinases (MMPs) is involved in positively and negatively affecting stroke outcome. Novel, noninvasive, multimodal imaging methods visualizing microglial and MMP alterations were employed. The spatio-temporal dynamics of these parameters were studied in relation to blood flow changes. Micro positron emission tomography (μPET) using [F]BR-351 showed MMP activity within the first days after transient middle cerebral artery occlusion (tMCAo), followed by increased [F]DPA-714 uptake as a marker for microglia activation with a maximum at 14 days after tMCAo. The inflammatory response was spatially located in the infarct core and in adjacent (penumbral) tissue. For the first time, multimodal imaging based on PET, single photon emission computed tomography, and magnetic resonance imaging revealed insight into the spatio-temporal distribution of critical parameters of poststroke inflammation. This allows further evaluation of novel treatment paradigms targeting the postischemic inflammation.

Epigenomic changes are an important feature of malignant tumors. How tumor aggressiveness is affected by DNA methylation of specific loci is largely unexplored. In genome-wide DNA methylation analyses, we identified the KCa 3.1 channel gene (KCNN4) promoter to be hypomethylated in an aggressive non-small-cell lung carcinoma (NSCLC) cell line and in patient samples. Accordingly, KCa 3.1 expression was increased in more aggressive NSCLC cells. Both findings were strong predictors for poor prognosis in lung adenocarcinoma. Increased KCa 3.1 expression was associated with aggressive features of NSCLC cells. Proliferation and migration of pro-metastatic NSCLC cells depended on KCa 3.1 activity. Mechanistically, elevated KCa 3.1 expression hyperpolarized the membrane potential, thereby augmenting the driving force for Ca(2+) influx. KCa 3.1 blockade strongly reduced the growth of xenografted NSCLC cells in mice as measured by positron emission tomography-computed tomography. Thus, loss of DNA methylation of the KCNN4 promoter and increased KCa 3.1 channel expression and function are mechanistically linked to poor survival of NSCLC patients.

Purpose: To evaluate between-site agreement of apparent diffusion coefficient (ADC) measurements in preclinical magnetic resonance imaging (MRI) systems. Materials and Methods: A miniaturized thermally stable ice-water phantom was devised. ADC (mean and interquartile range) was measured over several days, on 4.7T, 7T, and 9.4T Bruker, Agilent, and Magnex small-animal MRI systems using a common protocol across seven sites. Day-to-day repeatability was expressed as percent variation of mean ADC between acquisitions. Cross-site reproducibility was expressed as 1.96 x standard deviation of percent deviation of ADC values. Results: ADC measurements were equivalent across all seven sites with a cross-site ADC reproducibility of 6.3%. Mean day-to-day repeatability of ADC measurements was 2.3%, and no site was identified as presenting different measurements than others (analysis of variance [ANOVA] P = 0.02, post-hoc test n.s.). Between-slice ADC variability was negligible and similar between sites (P = 0.15). Mean within-region-of-interest ADC variability was 5.5%, with one site presenting a significantly greater variation than the others (P = 0.0013). Conclusion: Absolute ADC values in preclinical studies are comparable between sites and equipment, provided standardized protocols are employed.

Background: Longitudinal research is critical for understanding the biological mechanisms underlying the development of depression. Researchers recruit high-risk cohorts to understand how risk is transmitted from one generation to the next. Biological measurements have been incorporated into these longitudinal high-risk (LHR) studies in order to illuminate mechanistic pathways. Methods: To frame our review, we first present heritability estimates along the gene-by-environment continuum as a foundation. We then offer a Biomarkers of Intergenerational Risk for Depression (BIRD) model to describe the multiple hits individuals at risk receive and to allow for greater focus on the interactive effects of markers. BIRD allows for the known multifinality of pathways towards depression and considers the context (i.e., environment) in which these mechanisms emerge. Next, we review the extant LHR cohort studies that have assessed central nervous system (electroencephalography (EEG), neuroimaging), endocrine (hypothalamic–pituitary–adrenal axis (HPA)/cortisol), autonomic (startle, heart rate), genetic, sleep, and birth characteristics. Results: Results to date, in conjunction with the proposed model, point towards several pathways of discovery in understanding mechanisms, providing clear direction for future research examining potential endophenotypes. Limitations: Our review is based on relatively narrow inclusion and exclusion criteria. As such, many interesting studies were excluded, but this weakness is offset by strengths such as the increased reliability of findings. Conclusions: Blanket prevention programs are inefficient and plagued by low effect sizes due to low rates of actual conversion to disorder. The inclusion of biomarkers of risk may lead to enhanced program efficiency by targeting those at greatest risk.

Sarcopenia and frailty are common geriatric syndromes and are associated with adverse health outcome and impaired health-related quality of life. Co-occurrences of these two syndromes with age-related neurological diseases are potentially high but not well investigated. Moreover, it is not well understood how these syndromes interact with neurological diseases, such as Parkinson's disease, Alzheimer's disease and stroke. This article introduces the currently most accepted concepts of sarcopenia and frailty, discusses the potential relevance of the syndromes for geriatric patients and presents examples of studies that investigated potential interactions between these geriatric and neurological syndromes and conditions. First results indicate that (i) the co-occurrence of these geriatric syndromes and age-related neurological diseases is high, (ii) sarcopenia and frailty can influence the clinical state of neurological diseases to a relevant extent and (iii) at least some common causes and pathophysiological processes confer the geriatric and neurological conditions. In conclusion, profound knowledge about the interaction of sarcopenia, frailty and age-associated neurological conditions is currently not available. Such knowledge would have an enormous potential for improved therapy of these neurological conditions.

Healthcare-associated infections are an important cause of inpatient morbidity and mortality (1). Infections with multidrug-resistant (MDR) gram-negative bacteria, especially carbapenem-resistant organisms, are of particular concern since their treatment is complicated by the paucity of active and reliable antibiotics and the limited availability of rapid and accurate diagnostics (2). In an era of organ shortages, transplant recipients, by nature of their underlying condition and anticipated clinical course, are at increased risk for infection with MDR organisms (3, 4). Given the impact of antimicrobial resistance in transplant recipients, defining fundamental strategies to prevent and manage infections will be critical for the advancement of transplantation. Here, we describe a fatal case of endocarditis and disseminated carbapenem-resistant Acinetobacter baumannii (CRAb) infection in a simultaneous pancreas-kidney transplant recipient. Our goal is to highlight the unappreciated virulence of A. baumannii and difficulties in recognizing and treating infections caused by CRAb after organ transplantation.

Many-core hardware is targeted specifically at obtaining high performance, but reaching high performance is often challenging because hardware-specific details have to be taken into account. Although there are many programming systems that try to alleviate many-core programming, some providing a high-level language, others providing a low-level language for control, none of these systems have a clear and systematic methodology as a foundation. In this article, we propose stepwise-refinement for performance: a novel, clear, and structured methodology for obtaining high performance on many-cores. We present a system that supports this methodology, offers multiple levels of abstraction to provide programmers a trade-off between high-level and low-level programming, and provides programmers detailed performance feedback. We evaluate our methodology with several widely varying compute kernels on two different many-core architectures: a Graphical Processing Unit GPU and the Xeon Phi. We show that our methodology gives insight in the performance, and that in almost all cases, we gain a substantial performance improvement using our methodology. Copyright © 2015 John Wiley & Sons, Ltd.