A critical assessment of algorithms and challenges in the development of a closed-loop artificial pancreas

The development of an artificial pancreas is placed in the context of the history of the field of feedback control systems, beginning with the water clock of ancient Greece, and including a discussion of current efforts in the control of complex systems. The first generation of artificial pancreas devices included two manipulated variables (insulin and glucose infusion) and nonlinear functions of the error (difference between desired and measured glucose concentration) to minimize hyperglycemia while avoiding hypoglycemia. Dynamic lags between insulin infusion and glucose measurement were relatively small for these intravenous-based systems. Advances in continuous glucose sensing, fast-acting insulin analogs, and a mature insulin pump market bring us close to commercial realization of a closed-loop artificial pancreas. Model predictive control is discussed in-depth as an approach that is well suited for a closed-loop artificial pancreas. A major challenge that remains is handling an unknown glucose disturbance (meal), and an approach is proposed to base a current insulin infusion action on the predicted effect of a meal on future glucose values. Better "meal models" are needed, as a limited knowledge of the effect of a meal on the future glucose values limits the performance of any control algorithm.     

Algorithms for a Closed-Loop Artificial Pancreas: The Case for Model Predictive Control

The relative merits of model predictive control (MPC) and proportional-integral-derivative (PID) control are discussed, with the end goal of a closed-loop artificial pancreas (AP). It is stressed that neither MPC nor PID are single algorithms, but rather are approaches or strategies that may be implemented very differently by different engineers. The primary advantages to MPC are that (i) constraints on the insulin delivery rate (and/or insulin on board) can be explicitly included in the control calculation; (ii) it is a general framework that makes it relatively easy to include the effect of meals, exercise, and other events that are a function of the time of day; and (iii) it is flexible enough to include many different objectives, from set-point tracking (target) to zone (control to range). In the end, however, it is recognized that the control algorithm, while important, represents only a portion of the effort required to develop a closed-loop AP. Thus, any number of algorithms/approaches can be successful—the engineers involved in the design must have experience with the particular technique, including the important experience of implementing the algorithm in human studies and not simply through simulation studies.     

Overt albuminuria predicts diabetic retinopathy in Hispanics with NIDDM

Non-insulin-dependent diabetes mellitus (NIDDM) occurs with a higher frequency in Hispanic as compared with non-Hispanic whites. It also appears that there is a higher prevalence of diabetic nephropathy in the Hispanic population when compared with non-Hispanic whites. In the current study, 144 Hispanics and 671 non-Hispanic white NIDDM subjects were studied to determine the possible association of various risk factors and diabetic complications, including overt albuminuria, with diabetic retinopathy. Stereoscopic retinal fundus photographs were obtained and graded by the University of Wisconsin Fundus Photographic Reading Center. We also sought to determine whether risk factors for retinopathy vary between Hispanics and non-Hispanic whites. In the total group, duration of diabetes, glycosylated hemoglobin, neuropathy, diastolic hypertension, use of insulin, and Hispanic ethnicity correlated with the presence of retinopathy. Controlling for severity and duration of diabetes, Hispanics had a significantly increased risk of retinopathy relative to non-Hispanic whites (OR = 2.13, 95% CI = 1.34, 3.37, P = 0.0013). Duration of diabetes and presence of neuropathy were significantly correlated with the presence of diabetic retinopathy in Hispanics and non-Hispanic whites. The presence of overt albuminuria (>200 microg/min), although not related to diabetic retinopathy in non-Hispanic whites, conferred a high risk for diabetic retinopathy in Hispanics (OR = 11.14, CI = 1.20, 103.39, P = 0.0339) independent of other risk factors. In summary, Hispanics with NIDDM have an increased prevalence of diabetic retinopathy when compared with non-Hispanic whites. In addition, overt albuminuria in the Hispanic subjects appears to be a powerful predictor of the diabetic retinopathy.     

Subtle lung cancers: impact of edge enhancement and gray scale reversal on detection with digitized chest radiographs

The authors studied the impact of edge enhancement and gray scale polarity reversal on the detection of subtle lung cancers. Three experienced readers reviewed 46 biopsy-proved subtle lung cancers and 46 normal controls on chest radiographs that had been digitized into a 1,024 X 1,536-pixel matrix 8 bits deep. Receiver-operating characteristics (ROC) analysis of 1,656 pooled observations indicated that performance was best with the unmodified images (ROC area = 0.83), degraded by moderate enhancement of medium frequencies (ROC area = 0.80), and markedly impaired by severe enhancement of low frequencies (ROC area = 0.69). Gray scale polarity reversal further degraded performance (unenhanced ROC area = 0.74; moderately enhanced ROC area = 0.76; severely enhanced ROC area = 0.76). The authors conclude that edge enhancement and gray scale polarity reversal can impair the detectability of subtle lung cancers on digitized radiographs of medium resolution.     

Supracondylar fractures of the humerus: prediction of the cubitus varus deformity with CT

Rotation of the distal fracture fragment in the supracondylar fracture is a contributing factor in the development of the cubitus varus deformity. Computed tomography (CT) is superior to conventional radiography in the assessment of the position of fracture fragments and was used to study 20 patients with supracondylar fractures after reduction. These fractures were followed up with radiography until healed. As determined from CT scans, rotation of the distal fracture fragment of greater than 10 degrees resulted in an abnormal Baumann angle and a cubitus varus deformity in all patients. Use of CT should facilitate the identification of this complication and thus treatment of these fractures and prevention of subsequent deformity.     

放线瑞香宁碱的解热镇痛作用

从青藤科植物黑吹风(Illigera sp)总生物碱中分离出一个单体,经化学鉴定命名为放线瑞香宁碱(actinodapbnine简称Ac)。分子式C_(18)H_(17)NO_4,为10-甲氧基-1,2-(次甲二氧基)-6-去甲阿朴菲-9-醇(图1)。动物实验表明,Ac具有解痉、镇痛、局麻及降低小鼠体温等作用,并证明其镇痛作用系非中枢性。本文进一步研究其镇痛作用和对不同动物正常