We present a high-dimensional model of the representational space in human ventral temporal (VT) cortex in which dimensions are response-tuning functions that are common across individuals and ...patterns of response are modeled as weighted sums of basis patterns associated with these response tunings. We map response-pattern vectors, measured with fMRI, from individual subjects' voxel spaces into this common model space using a new method, “hyperalignment.” Hyperalignment parameters based on responses during one experiment—movie viewing—identified 35 common response-tuning functions that captured fine-grained distinctions among a wide range of stimuli in the movie and in two category perception experiments. Between-subject classification (BSC, multivariate pattern classification based on other subjects' data) of response-pattern vectors in common model space greatly exceeded BSC of anatomically aligned responses and matched within-subject classification. Results indicate that population codes for complex visual stimuli in VT cortex are based on response-tuning functions that are common across individuals.
► Response-tuning functions for visual population codes are common across individuals ► 35 response basis functions capture fine-grained distinctions among representations ► The common model space greatly improves between-subject classification of fMRI data ► The model has general validity across brains and across a wide range of stimuli
Aims The SCORE project was initiated to develop a risk scoring system for use in the clinical management of cardiovascular risk in European clinical practice. Methods and results The project ...assembled a pool of datasets from 12 European cohort studies, mainly carried out in general population settings. There were 205 178 persons (88 080 women and 117 098 men) representing 2.7 million person years of follow-up. There were 7934 cardiovascular deaths, of which 5652 were deaths from coronary heart disease. Ten-year risk of fatal cardiovascular disease was calculated using a Weibull model in which age was used as a measure of exposure time to risk rather than as a risk factor. Separate estimation equations were calculated for coronary heart disease and for non-coronary cardiovascular disease. These were calculated for high-risk and low-risk regions of Europe. Two parallel estimation models were developed, one based on total cholesterol and the other on total cholesterol/HDL cholesterol ratio. The risk estimations are displayed graphically in simple risk charts. Predictive value of the risk charts was examined by applying them to persons aged 45–64; areas under ROC curves ranged from 0.71 to 0.84. Conclusions The SCORE risk estimation system offers direct estimation of total fatal cardiovascular risk in a format suited to the constraints of clinical practice.
Large national reviews of patient charts estimate that approximately 10% of hospital admissions are associated with an adverse event (defined as an injury resulting in prolonged hospitalization, ...disability or death, caused by healthcare management). Apart from having a significant impact on patient morbidity and mortality, adverse events also result in increased healthcare costs due to longer hospital stays. Furthermore, a substantial proportion of adverse events are preventable. Through identifying the nature and rate of adverse events, initiatives to improve care can be developed. A variety of methods exist to gather adverse event data both retrospectively and prospectively but these do not necessarily capture the same events and there is variability in the definition of an adverse event. For example, hospital incident reporting collects only a very small fraction of the adverse events found in retrospective chart reviews. Until there are systematic methods to identify adverse events, progress in patient safety cannot be reliably measured. This review aims to discuss the need for a safety culture that can learn from adverse events, describe ways to measure adverse events, and comment on why current adverse event monitoring is unable to demonstrate trends in patient safety.
The already inadequate health systems of sub-Saharan Africa have been badly damaged by the emigration of their health professionals, a process in which the UK has played a prominent part. In 2005, ...there are special opportunities for the UK to take the lead in addressing that damage, and in focusing the attention of the G8 on the wider problems of health-professional migration from poor to rich countries. We suggest some practical measures to these ends. These include action the UK could take on its own, with the African countries most affected, and with other developed countries and WHO.
Despite extensive research on navigation, it remains unclear which features of an environment predict how difficult it will be to navigate. We analysed 478,170 trajectories from 10,626 participants ...who navigated 45 virtual environments in the research app-based game Sea Hero Quest. Virtual environments were designed to vary in a range of properties such as their layout, number of goals, visibility (varying fog) and map condition. We calculated 58 spatial measures grouped into four families: task-specific metrics, space syntax configurational metrics, space syntax geometric metrics, and general geometric metrics. We used Lasso, a variable selection method, to select the most predictive measures of navigation difficulty. Geometric features such as entropy, area of navigable space, number of rings and closeness centrality of path networks were among the most significant factors determining the navigational difficulty. By contrast a range of other measures did not predict difficulty, including measures of intelligibility. Unsurprisingly, other task-specific features (e.g. number of destinations) and fog also predicted navigation difficulty. These findings have implications for the study of spatial behaviour in ecological settings, as well as predicting human movements in different settings, such as complex buildings and transport networks and may aid the design of more navigable environments.
•We analysed 478,170 trajectories, 45 virtual environments and calculated 58 spatial metrics.•We grouped our metrics as: task-specific, space syntax configurational, space syntax geometric, general geometric metrics.•Environmental complexity (measured by entropy, number of rings and integration) is a predictor of navigation difficulty.•Number of decision points and accessibility of paths affect female participants' navigation performance.•Accessibility of paths (measured by axial integration) affects older participants' navigation performance.
Inter-subject alignment of functional MRI (fMRI) data is necessary for group analyses. The standard approach to this problem matches anatomical features of the brain, such as major anatomical ...landmarks or cortical curvature. Precise alignment of functional cortical topographies, however, cannot be derived using only anatomical features.
We propose a new inter-subject registration algorithm that aligns intra-subject patterns of functional connectivity across subjects. We derive functional connectivity patterns by correlating fMRI BOLD time-series, measured during movie viewing, between spatially remote cortical regions. We validate our technique extensively on real fMRI experimental data and compare our method to two state-of-the-art inter-subject registration algorithms. By cross-validating our method on independent datasets, we show that the derived alignment generalizes well to other experimental paradigms.
•Novel inter-subject registration algorithm based on functional connectivity•Improves alignment of functionally-defined areas•Extensively validated on real fMRI experimental data•Generalizes well to other experimental paradigms
Prostate cancer is the most common cancer in men worldwide. Despite its prevalence, there is a critical knowledge gap in understanding factors driving disparities in survival among different cohorts ...of patients with prostate cancer. Identifying molecular features separating disparate populations is an important first step in prostate cancer research that could lead to fundamental hypotheses in prostate biology, predictive biomarker discovery, and personalized therapy. N-linked glycosylation is a cotranslational event during protein folding that modulates a myriad of cellular processes. Recently, aberrant N-linked glycosylation has been reported in prostate cancers. However, the full clinical implications of dysregulated glycosylation in prostate cancer has yet to be explored. Herein, we performed direct on-tissue analysis of N-linked glycans using matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) from tissue microarrays of over 100 patient tumors with over 10 years of follow-up metadata. We successfully identified a panel of N-glycans that are unique between benign and prostate tumor tissue. Specifically, high-mannose as well as tri-and tetra-antennary N-glycans were more abundant in tumor tissue and increase proportionally with tumor grade. Further, we expanded our analyses to examine the N-glycan profiles of Black and Appalachian patients and have identified unique glycan signatures that correlate with recurrence in each population. Our study highlights the potential applications of MALDI-MSI for digital pathology and biomarker discovery for prostate cancer. IMPLICATIONS: MALDI-MSI identifies N-glycan perturbations in prostate tumors compared with benign tissue. This method can be utilized to predict prostate cancer recurrence and study prostate cancer disparities.
Purpose/Objectives ZAP-X, a novel and dedicated radiosurgery (SRS) system, has recently emerged, while CyberKnife has solidified its position as a versatile solution for SRS and stereotactic body ...radiation therapy over the past two decades. This study aims to compare the dosimetric performance and delivery efficiency of ZAP-X and CyberKnife in treating brain metastases of varying target sizes, employing circular collimation. Methods and materials Twenty-three patients, encompassing a total of 47 brain metastases, were included in the creation of comparative plans of ZAP-X and CyberKnife for analysis. The comparative plans were generated to achieve identical prescription doses for the targets, while adhering to the same dose constraints for organs at risk (OAR). The prescription isodose percentage was optimized within the range of 97–100% for each plan to ensure effective target-volume coverage. To assess plan quality, indices such as conformity, homogeneity, and gradient (CI, HI, and GI) were computed, along with the reporting of total brain volumes receiving 12Gy and 10Gy. Estimated treatment time and monitor units (MUs) were compared between the two modalities in evaluating delivery efficiency. Results Overall, CyberKnife achieved better CI and HI, while ZAP-X exhibited better GI and a smaller irradiated volume for the normal brain. The superiority of CyberKnife’s plan conformity was more pronounced for target size less than 1 cc and greater than 10 cc. Conversely, the advantage of ZAP-X’s plan dose gradient was more notable for target sizes under 10 cc. The homogeneity of ZAP-X plans, employing multiple isocenters, displayed a strong correlation with the target’s shape and the planner’s experience in placing isocenters. Generally, the estimated treatment time was similar between the two modalities, and the delivery efficiency was significantly impacted by the chosen collimation sizes for both modalities. Conclusion This study demonstrates that, within the range of target sizes within the patient cohort, plans generated by ZAP-X and CyberKnife exhibit comparable plan quality and delivery efficiency. At present, with the current platform of the two modalities, CyberKnife outperforms ZAP-X in terms of conformity and homogeneity, while ZAP-X tends to produce plans with a more rapid dose falloff.
Patients supported by mechanical ventilation require frequent invasive blood gas samples to monitor and adjust the level of support. We developed a transparent and novel blood gas estimation model to ...provide continuous monitoring of blood pH and arterial CO
in between gaps of blood draws, using only readily available noninvasive data sources in ventilated patients. The model was trained on a derivation dataset (1,883 patients, 12,344 samples) from a tertiary pediatric intensive care center, and tested on a validation dataset (286 patients, 4030 samples) from the same center obtained at a later time. The model uses pairwise non-linear interactions between predictors and provides point-estimates of blood gas pH and arterial CO
along with a range of prediction uncertainty. The model predicted within Clinical Laboratory Improvement Amendments of 1988 (CLIA) acceptable blood gas machine equivalent in 74% of pH samples and 80% of PCO
samples. Prediction uncertainty from the model improved estimation accuracy by 15% by identifying and abstaining on a minority of high-uncertainty samples. The proposed model estimates blood gas pH and CO
accurately in a large percentage of samples. The model's abstention recommendation coupled with ranked display of top predictors for each estimation lends itself to real-time monitoring of gaps between blood draws, and the model may help users determine when a new blood draw is required and delay blood draws when not needed.
Glycogen dysregulation is a hallmark of aging, and aberrant glycogen drives metabolic reprogramming and pathogenesis in multiple diseases. However, glycogen heterogeneity in healthy and diseased ...tissues remains largely unknown. Herein, we describe a method to define spatial glycogen architecture in mouse and human tissues using matrix‐assisted laser desorption/ionization mass spectrometry imaging. This assay provides robust and sensitive spatial glycogen quantification and architecture characterization in the brain, liver, kidney, testis, lung, bladder, and even the bone. Armed with this tool, we interrogated glycogen spatial distribution and architecture in different types of human cancers. We demonstrate that glycogen stores and architecture are heterogeneous among diseases. Additionally, we observe unique hyperphosphorylated glycogen accumulation in Ewing sarcoma, a pediatric bone cancer. Using preclinical models, we correct glycogen hyperphosphorylation in Ewing sarcoma through genetic and pharmacological interventions that ablate in vivo tumor growth, demonstrating the clinical therapeutic potential of targeting glycogen in Ewing sarcoma.
Synopsis
Development of a MALDI‐based assay for the spatial quantification of microenvironmental glycogen and glycogen biochemical architecture. Hyperphosphorylated glycogen was discovered in human Ewing sarcoma. Targeting tumor‐specific glycogen may be a potential therapeutic approach for Ewing sarcoma.
Development of a MALDI‐based assay for the spatial quantification of microenvironmental glycogen.
Ultra‐sensitivity allows visualization of glycogen in previously unknown but distinct cellular layers in multiple human tissues.
Identification of glycogen‐rich and glycogen‐poor tumors such as Ewing sarcoma and prostate cancer, respectively.
Targeting Ewing sarcoma glycogen by different modalities blunted tumor growth in immunodeficient mice.
Development of a MALDI‐based assay for the spatial quantification of microenvironmental glycogen and glycogen biochemical architecture. Hyperphosphorylated glycogen was discovered in human Ewing sarcoma. Targeting tumor‐specific glycogen may be a potential therapeutic approach for Ewing sarcoma.
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