常规剂量奥美拉唑治疗早产儿喂养不耐受的疗效研究

目的:探讨常规剂量奥美拉唑治疗早产儿喂养不耐受的疗效及对血清胃泌素(gastrin,GAS)的影响.方法:选取60例出现喂养不耐受的早产患儿随机分为2组,对照组30例给予常规处理,治疗组30例在常规治疗基础上于生后第4天开始给予奥美拉唑注射液静脉滴注(0.7mg/kg·d),1次/d,连用5天.采用放射免疫分析法测定治疗组血清胃泌素水平.结果:治疗组胃潴留及腹胀症状消失时间、恢复至出生体重所需日龄、足量胃肠道喂养时间、2周末奶量与对照组比较有显著差异(P＜0.01).治疗组血清GAS水平较对照组明显升高,差异有显著性(P＜0.05).结论:奥美拉唑促进早产儿胃泌素分泌,治疗早产儿喂养不耐受有显著疗效,未见不良反应,为早产儿喂养不耐受的治疗提供了新的治疗方法.     

Atomic level characterization of the nonproton ligand-sensing domain of ASIC3 channels

Acid-sensing ion channels (ASICs) are known to be primarily activated by extracellular protons. Recently, we characterized a novel nonproton ligand (2-guanidine-4-methylquinazoline, GMQ), which activates the ASIC3 channel subtype at neutral pH. Using an interactive computational-experimental approach, here we extend our investigation to delineate the architecture of the GMQ-sensing domain in the ASIC3 channels. We first established a GMQ binding mode and revealed that residues Glu-423, Glu-79, Leu-77, Arg-376, Gln-271, and Gln-269 play key roles in forming the GMQ-sensing domain. We then verified the GMQ binding mode using ab initio calculation and mutagenesis and demonstrated the critical role of the above GMQ-binding residues in the interplay among GMQ, proton, and Ca(2+) in regulating the function of ASIC3. Additionally, we showed that the same residues involved in coordinating GMQ responses are also critical for activation of the ASIC3(E79C) mutant by thiol-reactive compound DTNB. Thus, a range of complementary techniques provide independent evidence for the structural details of the GMQ-sensing domain at atomic level, laying the foundation for further investigations of endogenous nonproton ligands and gating mechanisms of the ASIC3 channels.     

On threats analysis approach applied to a Mediterranean remnant wetland: Is the assessment of human-induced threats related to different level of expertise of respondents?

Naming, listing and measuring human-induced threats in protected areas are crucial in conservation. Here, we defined a check-list of direct threats in a Mediterranean remnant wetland (central Italy), managed as nature reserve, grouping them according to a taxonomically-oriented nomenclature. We assessed three regime parameters (scope, severity, and magnitude) applying an experience-based method, then comparing the assessments obtained from two different level of expertise: a panel of independent people, upper level “university students” in an applied ecology class; and a panel of “experts” as nature reserve biologists and managers. Despite observing a significant correlation among values assigned from students and experts for each regime parameter, students underestimated the scope of feral dogs, the severity of fires and the magnitude of feral dogs and water stress. Considering only the magnitude values (sum of scope and severity), students assigned the higher values to alien species, antropophilous species, aircraft, and pollution, while the experts assigned the higher values to antropophilous species, aircraft, alien species, and water stress. In an order of priority, there was an agreement between students and experts with a coincidence for three threats out of four. We suppose that a panel of students with a short academic training could be useful to a get a first order of priority in regard to a set of local selected threats, with much similarity to the assessment obtained from a panel of experts. When threat metrics are difficult to compare, experience-based approach obtained from technicians trained ad hoc (“students”) could be useful to define priorities for management strategies in nature reserves, but data obtained should be examined critically. Indeed, students may assign higher scores to regime parameters of threats more readily identified and perceivable, underestimating the threats with an inconstant regime, localized in time and space, mobile, or cryptic. If experience-based methods are used to define scale of priorities, these issues need to be considered.     

Cenomanian–Turonian carbonate and organic-carbon isotope records, biostratigraphy and provenance of a key section in NE Sicily, Italy: Palaeoceanographic and palaeogeographic implications

In eastern Sicily, a series of highly organic-rich black shales occur as exotic blocks (~ 100 m across) floating in tectonized sediments (Argille Varicolori Unit containing olistoliths of Cretaceous–Palaeogene age). A 19-metre section, through one of these blocks near the town of Novara di Sicilia, includes cyclically bedded black shales, marlstones and claystones, which have been dated using planktonic foraminiferal and nannofossil biostratigraphy. On this basis, the section is assigned to the latest Cenomanian and clearly represents a manifestation of the Oceanic Anoxic Event characteristic of that interval. Total organic-carbon values range up to 23% and the relatively high hydrogen indices record the presence of marine organic matter of low thermal maturity. High-resolution carbonate and organic-carbon isotope curves are comparable with those recorded elsewhere in indicating a significant positive excursion and confirm that, in the Novara di Sicilia section, the black shales are latest Cenomanian in age. By comparison with Cenomanian–Turonian black shales exposed elsewhere in Italy (Calabianca section, western Sicily; Livello Bonarelli, Bottaccione Gorge, Gubbio, Marche–Umbria), the section of Novara di Sicilia is different in being more stratigraphically expanded. However, this section from eastern Sicily does resemble extremely closely coeval sediments cropping out in Tunisia and Morocco. This association is taken as evidence that the Argille Varicolori Unit includes elements that were initially deposited on the north African shelf during Cretaceous time.     

On the use of historical control information for trend test in carcinogenesis

In this article a new non-model-based significance test for detecting dose-response relationship with the incorporation of historical control data is proposed. This non-model-based test is considered simpler from a regulatory perspective because it does not require validating any modeling assumptions. Moreover, our test is especially appropriate to those studies in which the intravenous doses for the investigational chemical are labeled as, e.g., low, medium and high or the dose labels do not suggest any obvious choices of dose scores. This test can be easily adopted for detecting general dose-response shape, such as an umbrella pattern. Simple adjustments will be proposed for better control of the actual Type I error. Data sets from two carcinogenesis studies will be used to illustrate our method. We also evaluate the performance of the proposed test and the famous model-based Tarone's trend test with respect to size and power.     

Multiple Testing for Identifying Effective and Safe Treatments

In the literature various multiple test procedures to compare k treatments with a control have been investigated. They can be applied to establish either treatment efficacy or treatment safety. In this paper we propose procedures which control the multiple level α with respect to efficacy and safety simultaneously. On the one hand we consider a method with stagewise rejective adjustments of local levels applied to appropriately defined subfamilies of null hypotheses. When order restrictions are assumed to hold among the parameters of interest we can alternatively split the multiple level between the families of efficacy and safety null hypotheses. If either all treatments are declared to be safe or all are declared to be effective then the other family can be tested at the full multiple level α, respectively. The methods are compared in a simulation study.     

Acute exposure and chronic retention of aluminum in three vaccine schedules and effects of genetic and environmental variation

Like the mechanisms of action as adjuvants, the pharmacodynamics of injected forms of aluminum commonly used in vaccines are not well-characterized, particularly with respect to how differences in schedules impact accumulation and how factors such as genetics and environmental influences on detoxification influence clearance. Previous modeling efforts are based on very little empirical data, with the model by Priest based on whole-body clearance rates estimated from a study involving a single human subject. In this analysis, we explore the expected acute exposures and longer-term whole-body accumulation/clearance across three vaccination schedules: the current US Centers for Disease Control and Prevention (CDC) schedule, the current CDC schedule using low aluminum or no aluminum vaccines, and Dr. Paul Thomas’ “Vaccine Friendly Plan” schedule. We then study the effects of an implicit assumption of the Priest model on whether clearance dynamics from successive doses are influenced by the current level of aluminum or modeled by the assumption that a new dose has its own whole-body dynamics “reset” on the day of injection. We model two additional factors: variation (deficiency) in aluminum detoxification, and a factor added to the Priest equation to model the potential impact of aluminum itself on cellular and whole-body detoxification. These explorations are compared to a previously estimated pediatric dose limit (PDL) of whole-body aluminum exposure and provide a new statistic: %alumTox, the (expected) percentage of days (or weeks) an infant is in aluminum toxicity, reflecting chronic toxicity. We show that among three schedules, the CDC schedule results in the highest %alumTox regardless of model assumptions, and the Vaccine Friendly Plan schedule, which avoids >1 ACV per office visit results in the lowest (expected) %alumTox. These results are conservative, as the MSL is derived from data used by FDA to estimate safety of aluminum in adult humans. These results demonstrate high potential utility of modeling variation in patient responses to aluminum. More empirical data from individuals who are suspected of being intolerant of aluminum from vaccines, evidenced by high aluminum retention, neurodevelopmental disorders and/or a myriad of chronic illnesses would help answer questions on whether the model predictions can be used to estimate parameter values tied to genetic factors including genomic sequence variation and family history of chronic illnesses tied to aluminum exposure.     

Image segmentation methods for intracranial aneurysm haemodynamic research

Patient-specific haemodynamic technology is being increasingly utilised in clinical applications. Under normal circumstances, computational haemodynamic simulation is performed using geometric results obtained via medical image segmentation. However, even when employed upon the same set of medical imaging data, both the geometry and volume of intracranial aneurysm models are highly dependent upon varying insufficiently validated vascular segmentation methods. In this study, we compared three segmentation methods to segment the geometry of the aneurysm. These include: the Region Growing Threshold (RGT), Chan-Vese model (CV) and Threshold-Based Level Set (TLS). The results obtained were evaluated via measurement of arterial volume differences (VD), local geometric shapes, and haemodynamic simulation results. In total, 45 patient-specific aneurysm cases with three different anatomy locations were assessed in this study. From this, we discovered that the average VD of all three segmentation methods lay in the vicinity of 9.3% (SD=±4.6%). The computational haemodynamic simulation was performed via the use of the vessel geometries. Analyses produced an average of 23.2% (SD=±8.7%) difference in energy loss (EL) between the varying segmentation methods, with the difference in Wall Shear Stress (WSS) averaging 24.0% (SD=±8.5%) and 126.4% (SD=±124.4%) for the highest and lowest volumes of WSS respectively. The results of the lowest WSS, was seen to be significantly dependent upon the geometry of the aneurysm surface. It is therefore essential, in order to confirm the quality of segmentation processes in the application of patient-specific analyses of cerebrovascular haemodynamics – to validate these individual segmentation methods.