Statistical inference for decision curve analysis,with applications to cataract diagnosis

Statistical learning methods are widely used in medical literature for the purpose of diagnosis or prediction. Conventional accuracy assessment via sensitivity, specificity, and ROC curves does not fully account for clinical utility of a specific model. Decision curve analysis (DCA) becomes a novel complement as it incorporates a clinical judgment of the relative value of benefits (treating a true positive case) and harms (treating a false positive case) associated with prediction models. The preference of a patient or a policy-maker is formulated statistically as the underlying threshold probability, above which the patient would choose to be treated. Net benefit is then calculated for possible threshold probability, which places benefits and harms on the same scale. We consider the inference problems for DCA in this paper. Interval estimation procedure and inference methodology are provided after we derive the relevant asymptotic properties. Our formulation can accommodate the classification problems with multiple categories. We carry out numerical studies to assess the performance of the proposed methods. An eye disease dataset is analyzed to illustrate our proposals.     

The functional and structural changes in the basilar artery due to overpressure blast injury

Overpressure blast-wave induced brain injury (OBI) leads to progressive pathophysiologic changes resulting in a reduction in brain blood flow, blood brain barrier breakdown, edema, and cerebral ischemia. The aim of this study was to evaluate cerebral vascular function after single and repeated OBI. Male Sprague-Dawley rats were divided into three groups: Control (Naive), single OBI (30 psi peak pressure, 1 to 2 msec duration), and repeated (days 1, 4, and 7) OBI (r-OBI). Rats were killed 24 hours after injury and the basilar artery was isolated, cannulated, and pressurized (90 cm H₂O). Vascular responses to potassium chloride (KCl) (30 to 100 mmol/L), endothelin-1 (10⁻¹² to 10⁻⁷ mol/L), acetylcholine (ACh) (10⁻¹⁰ to 10⁻⁴ mol/L) and diethylamine-NONO-ate (DEA-NONO-ate) (10⁻¹⁰ to 10⁻⁴ mol/L) were evaluated. The OBI resulted in an increase in the contractile responses to endothelin and a decrease in the relaxant responses to ACh in both single and r-OBI groups. However, impaired DEA-NONO-ate-induced vasodilation and increased wall thickness to lumen ratio were observed only in the r-OBI group. The endothelin-1 type A (ET_A) receptor and endothelial nitric oxide synthase (eNOS) immunoreactivity were significantly enhanced by OBI. These findings indicate that both single and r-OBI impairs cerebral vascular endothelium-dependent dilation, potentially a consequence of endothelial dysfunction and/or vascular remodelling in basilar arteries after OBI.     

A KRT1 gene mutation related to epidermolytic ichthyosis in a Chinese family

We report a Chinese family with members affected by epidermolytic ichthyosis (EI), caused by KRT gene mutations. The proband was a 14‐year‐old boy who had simultaneous appearance of nephroblastoma and epidermolytic ichthyosis (EI). Both the patient and his mother exhibited the specific clinical and pathological manifestations of EI. We analysed all exons and flanking sequences of the KRT1 and KRT10 genes using PCR, and found that the proband and his mother had a G>C transition at nucleotide position 1432 in exon 7 of KRT1, resulting in an amino acid substitution of glutamate (GAA) to glutamine (CAA) at codon 478 (E478Q). The KRT10 gene had no mutations.