38 research outputs found
Forecasting Human-Object Interaction: Joint Prediction of Motor Attention and Actions in First Person Video
We address the challenging task of anticipating human-object interaction in
first person videos. Most existing methods ignore how the camera wearer
interacts with the objects, or simply consider body motion as a separate
modality. In contrast, we observe that the international hand movement reveals
critical information about the future activity. Motivated by this, we adopt
intentional hand movement as a future representation and propose a novel deep
network that jointly models and predicts the egocentric hand motion,
interaction hotspots and future action. Specifically, we consider the future
hand motion as the motor attention, and model this attention using latent
variables in our deep model. The predicted motor attention is further used to
characterise the discriminative spatial-temporal visual features for predicting
actions and interaction hotspots. We present extensive experiments
demonstrating the benefit of the proposed joint model. Importantly, our model
produces new state-of-the-art results for action anticipation on both EGTEA
Gaze+ and the EPIC-Kitchens datasets. Our project page is available at
https://aptx4869lm.github.io/ForecastingHOI
Single Nucleotide Polymorphism (SNP)-Based Loss of Heterozygosity (LOH) Testing by Real Time PCR in Patients Suspect of Myeloproliferative Disease
During tumor development, loss of heterozygosity (LOH) often occurs. When LOH is preceded by an oncogene activating mutation, the mutant allele may be further potentiated if the wild-type allele is lost or inactivated. In myeloproliferative neoplasms (MPN) somatic acquisition of JAK2V617F may be followed by LOH resulting in loss of the wild type allele. The occurrence of LOH in MPN and other proliferative diseases may lead to a further potentiating the mutant allele and thereby increasing morbidity. A real time PCR based SNP profiling assay was developed and validated for LOH detection of the JAK2 region (JAK2LOH). Blood of a cohort of 12 JAK2V617F-positive patients (n = 6 25–50% and n = 6>50% JAK2V617F) and a cohort of 81 patients suspected of MPN was stored with EDTA and subsequently used for validation. To generate germ-line profiles, non-neoplastic formalin-fixed paraffin-embedded tissue from each patient was analyzed. Results of the SNP assay were compared to those of an established Short Tandem Repeat (STR) assay. Both assays revealed JAK2LOH in 1/6 patients with 25–50% JAK2V617F. In patients with >50% JAK2V617F, JAK2LOH was detected in 6/6 by the SNP assay and 5/6 patients by the STR assay. Of the 81 patients suspected of MPN, 18 patients carried JAK2V617F. Both the SNP and STR assay demonstrated the occurrence of JAK2LOH in 5 of them. In the 63 JAK2V617F-negative patients, no JAK2LOH was observed by SNP and STR analyses. The presented SNP assay reliably detects JAK2LOH and is a fast and easy to perform alternative for STR analyses. We therefore anticipate the SNP approach as a proof of principle for the development of LOH SNP-assays for other clinically relevant LOH loci
VPS29 Is Not an Active Metallo-Phosphatase but Is a Rigid Scaffold Required for Retromer Interaction with Accessory Proteins
VPS29 is a key component of the cargo-binding core complex of retromer, a protein assembly with diverse roles in transport of receptors within the endosomal system. VPS29 has a fold related to metal-binding phosphatases and mediates interactions between retromer and other regulatory proteins. In this study we examine the functional interactions of mammalian VPS29, using X-ray crystallography and NMR spectroscopy. We find that although VPS29 can coordinate metal ions Mn2+ and Zn2+ in both the putative active site and at other locations, the affinity for metals is low, and lack of activity in phosphatase assays using a putative peptide substrate support the conclusion that VPS29 is not a functional metalloenzyme. There is evidence that structural elements of VPS29 critical for binding the retromer subunit VPS35 may undergo both metal-dependent and independent conformational changes regulating complex formation, however studies using ITC and NMR residual dipolar coupling (RDC) measurements show that this is not the case. Finally, NMR chemical shift mapping indicates that VPS29 is able to associate with SNX1 via a conserved hydrophobic surface, but with a low affinity that suggests additional interactions will be required to stabilise the complex in vivo. Our conclusion is that VPS29 is a metal ion-independent, rigid scaffolding domain, which is essential but not sufficient for incorporation of retromer into functional endosomal transport assemblies
Erratum to: Methods for evaluating medical tests and biomarkers
[This corrects the article DOI: 10.1186/s41512-016-0001-y.]
A View from the Past Into our Collective Future: The Oncofertility Consortium Vision Statement
Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future
Spitzer Matching Survey of the UltraVISTA Ultra-deep Stripes (SMUVS):Full-mission IRAC Mosaics and Catalogs
This paper describes new deep 3.6 and 4.5 micron imaging of three UltraVISTA
near-infrared survey stripes within the COSMOS field. The observations were
carried out with Spitzer's Infrared Array Camera (IRAC) for the Spitzer
Matching Survey of the Ultra-VISTA Deep Stripes (SMUVS). In this work we
present our data reduction techniques, and document the resulting mosaics,
coverage maps, and catalogs in both IRAC passbands for the three easternmost
UltraVISTA survey stripes, covering a combined area of about 0.66 square
degrees, of which 0.45 square degrees have at least 20 hr integration time.
SMUVS reaches point-source sensitivities of about 25.0 AB mag at both 3.6 and
4.5 microns with a significance of 4-sigma accounting for both survey
sensitivity and source confusion. To this limit the SMUVS catalogs contain a
total of about 350,000 sources, each of which is detected significantly in at
least one IRAC band. Because of its uniform and high sensitivity, relatively
large area coverage, and the wide array of ancillary data available in COSMOS,
the SMUVS survey will be useful for a large number of cosmological
investigations. We will make all images and catalogues described herein
publicly available via the Spitzer Science Center.Comment: Accepted for publication by ApJS. The main text has been expanded and
some figures have been updated in response to the referee's comments. Except
for additions to error flag descriptors, the catalogs and the conclusions are
unchanged from previous version
TMS stimulation over the inferior parietal cortex disrupts prospective sense of agency
Sense of agency refers to the feeling of controlling an external event through one's own action. On one influential view, sense of agency is inferred after an action, by "retrospectively" comparing actual effects of actions against their intended effects. However, it has been recently shown that earlier processes, linked to action selection, may also contribute to sense of agency, in advance of the action itself, and independently of action effects. The inferior parietal cortex (IPC) may underpin this "prospective" contribution to agency, by monitoring signals relating to fluency of action selection in dorsolateral prefrontal cortex (DLPFC). Here, we combined transcranial stimulation (TMS) with subliminal priming of action selection to investigate the causal role of these regions in the prospective coding of agency. In a first experiment, we showed that TMS over left IPC at the time of action selection disrupts perceived control over subsequent effects of action. In a second experiment, we exploited the temporal specificity of single-pulse TMS to pinpoint the exact timing of IPC contribution to sense of agency. We replicated the reduction in perceived control at the point of action selection, while observing no effect of TMS-induced disruption of IPC at the time of action outcomes
Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments
Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests
Erratum to: Methods for evaluating medical tests and biomarkers
[This corrects the article DOI: 10.1186/s41512-016-0001-y.]
Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study
Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe