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Institute
Highlights
• A panel of 20 biomarkers was identified capable of differentiating BD patients from controls.
• Excellent discrimination between established BD patients and controls.
• Good to excellent discrimination between misdiagnosed BD patients and first onset MDD patients.
• Fair to good discrimination between pre-diagnostic BD patients and controls.
• Study demonstrates the potential utility of a protein biomarker panel as a diagnostic test for BD.
Abstract
Background: Bipolar disorder (BD) is a costly, devastating and life shortening mental disorder that is often misdiagnosed, especially on initial presentation. Misdiagnosis frequently results in ineffective treatment. We investigated the utility of a biomarker panel as a diagnostic test for BD.
Methods and findings: We performed a meta-analysis of eight case-control studies to define a diagnostic biomarker panel for BD. After validating the panel on established BD patients, we applied it to undiagnosed BD patients. We analysed 249 BD, 122 pre-diagnostic BD, 75 pre-diagnostic schizophrenia and 90 first onset major depression disorder (MDD) patients and 371 controls. The biomarker panel was identified using ten-fold cross-validation with lasso regression applied to the 87 analytes available across the meta-analysis studies.
We identified 20 protein analytes with excellent predictive performance [area under the curve (AUC) ⩾ 0.90]. Importantly, the panel had a good predictive performance (AUC 0.84) to differentiate 12 misdiagnosed BD patients from 90 first onset MDD patients, and a fair to good predictive performance (AUC 0.79) to differentiate between 110 pre-diagnostic BD patients and 184 controls. We also demonstrated the disease specificity of the panel.
Conclusions: An early and accurate diagnosis has the potential to delay or even prevent the onset of BD. This study demonstrates the potential utility of a biomarker panel as a diagnostic test for BD.
Studies have demonstrated an increased risk of accidents and injuries in children, adolescents and adults with attention-deficit/hyperactivity disorder (ADHD). However, little is known about how accident risk may alter over the lifespan. Additionally, it would be important to know if the most common types of accidents and injuries differ in ADHD patients over different age groups. Furthermore, there is increasing evidence of an ameliorating effect of ADHD medication on accident risk. Lastly, the underlying risk factors and causal mechanisms behind increased accident risk remain unclear. We therefore conducted a systematic review focusing on the above described research questions. Our results suggested that accident/injury type and overall risk changes in ADHD patients over the lifespan. ADHD medication appeared to be similarly effective at reducing accident risk in all age groups. However, studies with direct comparisons of accident/injuries and effects of medication at different age groups or in old age are still missing. Finally, comorbidities associated with ADHD such as substance abuse appear to further increase the accident/injury risk.
The prize-collecting vehicle routing problem with single and multiple depots and non-linear cost
(2013)
In this paper, we propose a new routing problem to model a highly relevant planning task in small package shipping. We consider the Prize-Collecting Vehicle Routing Problem with Non-Linear cost in its single and multi-depot version, which integrates the option of outsourcing customers to subcontractors instead of serving them with the private fleet. Thereby, a lower bound on the total customer demand to be served by the private fleet guarantees a high utilization of the fleet capacity. To represent the practical situation, where a discount is given by a subcontractor if larger amounts of packages are outsourced, subcontracting costs follow a non-linear function. The considered problem is NP-hard and we propose an Adaptive Variable Neighborhood Search algorithm to solve instances of realistic size. We propose new benchmark sets for the single and the multi-depot problem, which are adapted from test instances of the capacitated VRP and the closely related Multi-Depot VRP with Private fleet and Common carrier. In numerical studies, we investigate the performance of our algorithm on the newly generated test instances and on standard benchmark problems of related problems. Moreover, we study the effect of different cost functions and different values of the minimal demand to be served by the private fleet on the routing solutions obtained.