Neuropsychological profile and social cognition in congenital central hypoventilation syndrome (CCHS): Correlation with neuroimaging in a clinical case

Introduction: Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder due to paired-like homeobox gene (PHOX2B) mutations. CCHS patients suffer from dysregulation of the autonomic nervous system characterized by the absence of or extremely reduced response to hypercapnia and hypoxia, with neuropsychological deficits. The aim of this exploratory study is to describe the longitudinal neuropsychological profile and its correlations with magnetic resonance imaging (MRI) of a child with CCHS with a PHOX2B mutation. Method: A comprehensive neuropsychological evaluation was conducted serially at age 7 years 4 months and 10 years 3 months, including assessment of intellectual functioning (IQ), motor functioning, perception, attention, executive functions, language, memory, social cognition, academic skills, and psychopathology. Reliable change index (RCI) scores were used to assess changes between assessments. We collected spin lattice relaxation time (T1)-weighted, fluid-attenuated inversion recovery (FLAIR), and spin spin lattice relaxation time (T2)-weighted images from the child at age 10 years 3 months using a 1.5-tesla MRI scanner. Results: IQ, processing speed index (PSI), social cognition (theory of mind and facial emotion recognition), selective attention, naming, academic skills (reading/comprehension), and manual speed with right hand declined in the second evaluation relative to the initial evaluation, while visuoconstructional praxis, receptive vocabulary, working memory, and arithmetic skill improved. The patient showed a remarkable global deterioration in executive functions (planning, task flexibility, behavioral regulation, and metacognition) as revealed by parental report and clinical evaluation. MRI revealed gliosis from the head to tail of the hippocampus and thinning of parahippocampal gyri. Conclusions: In a clinical case of CCHS, serial evaluation revealed deterioration of executive functions and social cognition over a 3-year interval. These changes corresponded to hippocampal damage as revealed in MRI, which may have affected social cognition through its role in the default mode network. Serial neuropsychological assessment is clinically useful in managing the needs of these patients.     

Digital Image Analysis Is a Useful Adjunct to Endoscopic Ultrasonographic Diagnosis of Subepithelial Lesions of the Gastrointestinal Tract

Objective. The purpose of this study was to explore the role of digital image analysis in differentiating endoscopic ultrasonographic (EUS) features of potentially malignant gastrointestinal subepithelial lesions (SELs) from those of benign lesions. Methods. Forty‐six patients with histopathologically confirmed gastrointestinal stromal tumors (GISTs), carcinoids, and lipomas who had undergone EUS evaluation were identified from our database. Representative regions of interest (ROIs) were selected from the EUS images, and features were extracted by texture analysis. On the basis of these features, an artificial neural network (ANN) was built, trained, and internally validated by unsupervised learning followed by supervised learning. Outcomes were the performance characteristics of the ANN. Results. A total of 106, 111, and 124 ROIs were selected from EUS images of 8, 10, and 28 patients with lipomas, carcinoids, and GISTs, respectively. For each ROI, 228 statistical parameters were extracted and later reduced to the 11 most informative features by principal component analysis. After training with 50% of the data, the remainder of the data were used to validate the ANN. The model was “good” in differentiating carcinoids and GISTs, with area under the receiver operating characteristic curve (AUC) values of 0.86 and 0.89, respectively. The model was “excellent” in identifying lipomas correctly, with an AUC of 0.92. Conclusions. Digital image analysis of EUS images is a useful noninvasive adjunct to EUS evaluation of SELs.     

A Decision-Theoretic Method for Assessing a Change in the Rate of Non-Acceptable Inpatient Claims

A health care measure that assesses the occurrence or non-occurrence of an event may be costly to obtain. For instance, measuring whether an inpatient hospital stay was necessary according to accepted clinical protocols is a relevant, though expensive analysis. Prior research (Rosenberg, 1998; Rosenberg, et al., 1999; Rosenberg and Griffith, 2000) has shown that a Bayesian logistic regression model is an excellent tool to predict the rate of Non-Acceptable inpatient hospital Claims (NACs).This paper describes a decision-theoretic approach to determine whether a change in the NAC rate warrants investigation. The Bayesian model is used to estimate, by principal discharge diagnosis, the posterior distribution of the NAC rate for a group of claims at the time of the audit (defined as time 0). This distribution of the NAC rate is compared against another posterior distribution of the NAC rate obtained at a later time (without further audit). Claim and investigation costs are included in the assessment of whether an investigation of a change in the NAC rate should be undertaken. This approach provides an inexpensive, supplemental level of control between audits for monitoring the level of the NAC rate. The methodology is also applicable to other health care measurements.     

Network of Contacts between Cattle Herds in a French Area Affected by Bovine Tuberculosis in 2010

France attained ‘Officially Tuberculosis‐Free’ status in 2000. However, the Côte d’Or department (a French administrative unit) has since seen an increase in bovine tuberculosis (bTB) cases, with 35% of cases attributed to neighbourhood contamination. The aim of this study was to investigate the characteristics of neighbourhood contacts in an area affected by bTB in 2010, through the use of social network methods. We carried out a survey to determine the frequency and distribution of between‐herd contacts in an area containing 22 farms. Contacts were weighted, as not all types of contact carried the same risk of bTB transmission. Cattle movement was considered to be associated with the highest risk, but was not observed within the studied area during the study period. Contact with wild boars was the most frequent type of contact, but was associated with a very low risk. Direct cattle‐to‐cattle contacts in pasture and contacts with badger latrines were less frequent, but entailed a greater risk of M. bovis transmission. Centrality values were heterogeneous in these two networks. This would enable the disease to spread more rapidly at the start of epidemics than in a perfect randomly mixed population. However, this situation should also result in the total number of infected herds being smaller. We attributed 95% of the contacts to direct contact in pasture or contact with wild boars or badger latrines. Other kinds of contact occurred less frequently (equipment sharing, cattle straying) or did not occur at all (attendance at a show). Most of the contact types were correlated, but none was sufficient in itself to account for all contacts between one particular farm and its neighbours. Contacts with neighbours therefore represent a challenge for the implementation or improvement of control measures.     

Bayesian空间泊松模型对小区域非传染病患病率的估计

目的为地理小区域非传染病患病率的估计及疾病地理分布情况的探讨提供方法学上的理论依据。方法以四川省2000年8～10岁儿童甲状腺肿大率为例，为克服甲状腺肿大的空间自相关性和异质性，构建Bayesian空间泊松模型，用Gibbs抽样的MCMC模型技术估计各县（区）的甲状腺肿大率。结果用Bayesian空间泊松模型得到的估计率与粗率相比，前者得到的非病区、中等病区及重病区数目比后者要少，轻病区数目要多。结论利用Bayesian空间泊松模型有利于消除抽样引起的极端值，使得其估计值比由原样本得到的粗率稳健。     

Robust non‐linear mixed modelling of longitudinal PSA levels after prostate cancer treatment

The objective of this study was to develop a robust non‐linear mixed model for prostate‐specific antigen (PSA) measurements after a high‐intensity focused ultrasound (HIFU) treatment for prostate cancer. The characteristics of these data are the presence of outlying values and non‐normal random effects. A numerical study proved that parameter estimates can be biased if these characteristics are not taken into account. The intra‐patient variability was described by a Student‐t distribution and Dirichlet process priors were assumed for non‐normal random effects; a process that limited the bias and provided more efficient parameter estimates than a classical mixed model with normal residuals and random effects. It was applied to the determination of the best dynamic PSA criterion for the diagnosis of prostate cancer recurrence, but could be used in studies that rely on PSA data to improve prognosis or compare treatment efficiencies and also with other longitudinal biomarkers that, such as PSA, present outlying values and non‐normal random effects. Copyright © 2010 John Wiley & Sons, Ltd.     

Explorations of the mean field theory learning algorithm

The mean field theory (MFT) learning algorithm is elaborated and explored with respect to a variety of tasks. MFT is benchmarked against the back-propagation learning algorithm (BP) on two different feature recognition problems: two-dimensional mirror symmetry and multidimensional statistical pattern classification. We find that while the two algorithms are very similar with respect to generalization properties, MFT normally requires a substantially smaller number of training epochs than BP. Since the MFT model is bidirectional, rather than feed-forward, its use can be extended naturally from purely functional mappings to a content addressable memory. A network with N visible and N hidden units can store up to approximately 4N patterns with good content-addressability. We stress an implementational advantage for MFT: it is natural for VLSI circuitry.     

Neuroendocrine activity of the melanocyte

Abstract:  More than 15 years ago, we have proposed that melanocytes are sensory and regulatory cells with computing capability, which transform external and/or internal signals/energy into organized regulatory network(s) for the maintenance of the cutaneous homeostasis. This concept is substantiated by accumulating evidence that melanocytes produce classical stress neurotransmitters, neuropeptides and hormones, express corresponding receptors and these processes are modified and/or regulated by ultraviolet radiation, biological factors or stress. Examples of the above are catecholamines, serotonin, N -acetyl-serotonin, melatonin, proopiomelanocortin-derived adrenocorticotropic hormone, β-endorphin or melanocyte-stimulating hormone peptides, corticotropin releasing factor, related urocortins and corticosteroids including cortisol and corticosterone as well as their precursors. Furthermore, their production is not random, but hierarchical and follows the structures of classical neuroendocrine organizations such as hypothalamic-pituitary-adrenal axis, serotoninergic, melatoninergic and catecholaminergic systems. An example of an intrinsic but overlooked neuroendocrine activity is production and secretion of melanogenesis intermediates including l -DOPA or its derivatives that could enter circulation and act on distant sites. Such capabilities have defined melanocytes as neuroendocrine cells that not only coordinate cutaneous but also can affect a global homeostasis.     

Efficacy of recombinant activated factor VII vs. activated prothrombin complex concentrate for patients suffering from haemophilia complicated with inhibitors: a Bayesian meta-regression

Summary.  The optimal on-demand treatment of joint bleeds in haemophilia patients with inhibitors is a source of debate, with studies reporting various efficacy levels for different drugs and dosage regimens. To analyse, in a unified Bayesian meta-regression model, the published efficacy of recombinant activated factor VII (rFVIIa) and/or activated prothrombin complex concentrate (aPCC) as on-demand treatments for joint bleeds in haemophilia patients with inhibitors. A systematic search was carried out to identify studies reporting on dosage and efficacy of rFVIIa and aPCC in the treatment of joint bleeds in the target patient population. Data were abstracted and included in the model and adjusted for potential sources of heterogeneity. Pooled efficacy levels for typical rFVIIa and aPCC regimens were estimated. Seventeen studies, collectively reporting on >2000 joint bleeds, were included. Medication type combined with dosage was the only significant explanatory parameter. The model predicts that a typical regimen of 90 μg kg⁻¹ rFVII repeated every 3 h if needed results in cumulative joint bleed resolution of 66%, 88% and 95% after 12, 24 and 36 h, respectively. In comparison, a typical regimen of 75 IU kg⁻¹ aPCC repeated every 12 h if needed results in cumulative joint bleed resolution of 39%, 62% and 76%, respectively. These differences were statistically significant and were also robust in sensitivity analyses. This analysis suggests that a typical rFVIIa regimen will resolve joint bleeds more effectively than a typical aPCC regimen after 12, 24 and 36 h.     

Sources of hepatic glucose production by 2H2O ingestion and Bayesian analysis of 2H glucuronide enrichment

The contribution of gluconeogenesis to hepatic glucose production (GP) was quantified after ²H₂O ingestion by Bayesian analysis of the position 2 and 5 ²H‐NMR signals (H2 and H5) of monoacetone glucose (MAG) derived from urinary acetaminophen glucuronide. Six controls and 10 kidney transplant (KTx) patients with cyclosporine A (CsA) immunosuppressant therapy were studied. Seven KTx patients were lean and euglycemic (BMI = 24.3 ± 1.0 kg/m²; fasting glucose = 4.7 ± 0.1 mM) while three were obese and hyperglycemic (BMI = 30.5 ± 0.7 kg/m²; fasting glucose = 7.1 ± 0.5 mM). For the 16 spectra analyzed, the mean coefficient of variation for the gluconeogenesis contribution was 10% ± 5%. This uncertainty was associated with a mean signal‐to‐noise ratio (SNR) of 79:1 and 45:1 for the MAG H2 and H5 signals, respectively. For control subjects, gluconeogenesis contributed 54% ± 7% of GP as determined by the mean and standard deviation (SD) of individual Bayesian analyses. For the lean/normoglycemic KTx subjects, the gluconeogenic contribution to GP was 62% ± 7% (P = 0.06 vs. controls), while hyperglycemic/obese KTx patients had a gluconeogenic contribution of 68% ± 3% (P < 0.005 vs. controls). These data suggest that in KTx patients, an increased gluconeogenic contribution to GP is strongly associated with obesity and hyperglycemia. Magn Reson Med 60:517–523, 2008. © 2008 Wiley‐Liss, Inc.