The Department of Health perspective on handling uncertainties in health sciences

Recognizing and working with uncertainty in handling risk are part of both clinical practice and the policy-making process. The Department of Health recognizes the inherent challenges that uncertainty brings and employs a wide range of research mechanisms, drawing on a diverse set of disciplines, to provide an evidence base to inform both policy creation and implementation, and clinical practice. This paper describes a variety of situations and the Government response to them, each time highlighting the use of science to reduce unknowns and to support decision-making. It highlights the need for a strong research infrastructure to support the Department's requirements, and those of the NHS, both in real time to respond to emergencies and to establish a high standard of care. However, although science provides a powerful tool to reduce uncertainty, it will not always produce definitive answers and often provides the start point for a dialogue between decision makers and researchers.     

Time-variable simulation of soil vapor intrusion into a building with a combined crawl space and basement

A time-variable one-dimensional model (called ViM for Vapor Intrusion Model)to predict indoor vapor concentrations in a dwelling with a combined basement and crawl space has been developed. ViM predicts vapor concentrations in each of the three compartments. Volatile chemicals that intrude into the dwelling are assumed to originate from soil, groundwater (where an attenuating plume is simulated), or ambient air. Processes included in the model are advection, diffusion, biodecay, and adsorption in the soil column; transport by diffusion and advection into individual crawl space and basement compartments; advection from each compartment into an overlying dwelling space; and exchange of ambient air and indoor air. The time-variable concentration fields are solved by first transforming the partial and ordinary differential equations into Laplace space, solving the resulting ordinary differential equations or algebraic equations, and numerically inverting those equations. This approach was an expedient way of handling the coupling between the subsurface and the dwelling. ViM was applied to a building (Building 20) located at the former Moffett Field Naval Air Station, in Mountain View, CA. The building is a former bachelor officer's quarters. The shallow groundwater beneath the building is contaminated with a number of volatile chemicals, including trichloroethene, cis-1,2-dichloroethene, and trans-1,2-dichloroethene, all of which were simulated. Using indoor air data collected in 2003-2004, and other field data collected prior to that time, the accuracy of the model's predictions was demonstrated. ViM's results were also compared against a version of the steady-state Johnson and Ettinger model (1) that was modified to accommodate a dwelling with a combined crawl space and basement (called the JEM model in this paper). The predictions from the JEM model were consistently higher than the predictions from ViM, but still near the upper range of the observed data.     

Reduction and survival of Listeria monocytogenes in ready-to-eat meats after irradiation

A five-strain Listeria monocytogenes culture was inoculated onto six different types of ready-to-eat (RTE) meats (frankfurters, ham, roast beef, bologna, smoked turkey with lactate, and smoked turkey without lactate). The meats were vacuum packed and stored at 4 degrees C for 24 h prior to irradiation. Populations of L. monocytogenes were recovered by surface plating on nonselective and selective media. The margins of safety studied include 3-log (3D) and 5-log (5D) reduction of pathogenic bacteria to achieve an optimal level of reduction while retaining organoleptic qualities of the meats. A 3-log reduction of L. monocytogenes was obtained at 1.5 kGy when nonselective plating medium was used. The dosages for 3-log reduction were 1.5 kGy for bologna, roast beef, and both types of turkey and 2.0 kGy for frankfurters and ham on the basis of use of selective medium. The D10-values ranged from 0.42 to 0.44 kGy. A 5-log reduction of L. monocytogenes was obtained at 2.5 kGy with nonselective medium. With selective medium, the dosages were 2.5 kGy for bologna, roast beef, and both types of turkey and 3.0 kGy for frankfurters and ham. Survival of L. monocytogenes in the same RTE meat types after irradiation was also studied. Meats were inoculated with 5 log L. monocytogenes per g and irradiated at doses of 2.0 and 4.0 kGy. Recovery of the surviving organisms was observed during storage at temperatures of 4 and 10 degrees C for 12 weeks. Preliminary results showed no growth in meats irradiated at 4.0 kGy. Survivors were observed for irradiated meats at 2.0 kGy stored at 10 degrees C after the second week. No growth was observed in samples irradiated at 2.0 kGy stored at 4 degrees C until the fifth week.     

Design and synthesis of conformationally constrained cyclophilin inhibitors showing a cyclosporin-A phenotype in C. elegans

Cyclophilin A (CypA) is a member of the immunophilin family of proteins and receptor for the immunosuppressant drug cyclosporin A (CsA). Here we describe the design and synthesis of a new class of small-molecule inhibitors for CypA that are based upon a dimedone template. Electrospray mass spectrometry is utilised as an initial screen to quantify the protein affinity of the ligands. Active inhibitors and fluorescently labelled derivatives are then used as chemical probes for investigating the biological role of cyclophilins in the nematode Caenorhabditis elegans.     

The effects of bilateral lesions of the amygdala on dyadic social interactions in rhesus monkeys (Macaca mulatta).

The role of the amygdala in dyadic social interactions of adult rhesus monkeys (Macaca mulatta) was assessed after bilateral ibotenic acid lesions. Social, nonsocial, and spatial behaviors of amygdalectomized and control monkeys were assessed in 3 dyadic experiments: constrained, unconstrained, and round robin. Lesions produced extensive bilateral damage to the amygdala. Across all experiments, the amygdalectomized monkeys demonstrated increased social affiliation, decreased anxiety, and increased confidence compared with control monkeys, particularly during early encounters. Normal subjects also demonstrated increased social affiliation toward the amygdalectomized subjects. These results indicate that amygdala lesions in adult monkeys lead to a decrease in the species-normal reluctance to immediately engage a novel conspecific in social behavior. The altered behavior of the amygdalectomized monkeys may have induced the increased social interactions from their normal companions. This is contrary to the idea that amygdalectomy produces a decrease in social interaction and increased aggression from conspecifics. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

漂白剂和表面活性剂的混合(英)

烷基二酚醚二磺酸盐表面活性剂可以很好地和漂白剂次氯酸钠混合 ,在含次氯酸钠的配方中 ,稳定性和溶解性均很好 ,不会促使漂白剂分解。     

The effects of vicarious exposure to the recent massacre at Virginia Tech.

The authors examined whether exposure to the April 2007 Virginia Tech school shootings would increase symptoms of acute stress in students at another university who were not personally involved, but who followed the case vicariously through news media. The authors ran a series of regression analyses using multinomial logit (MNL) models, a methodology which can be used for dealing with categorical outcome variables. The authors found that as TV viewing of the Virginia Tech case increased, the probability that a student would respond with moderate or acute stress symptoms also increased. The authors were able to describe the magnitude of the relationship between vicarious exposure to the Virginia Tech case and acute stress symptomatology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Role of Gut Microbiota in Overcoming Resistance to Checkpoint Inhibitors in Cancer Patients: Mechanisms and Challenges

The introduction of immune checkpoint inhibitors has constituted a major revolution in the treatment of patients with cancer. In contrast with the traditional cytotoxic therapies that directly kill tumor cells, this treatment modality enhances the ability of the host’s immune system to recognize and target cancerous cells. While immune checkpoint inhibitors have been effective across multiple cancer types, overcoming resistance remains a key area of ongoing research. The gut microbiota and its role in cancer immunosurveillance have recently become a major field of study. Gut microbiota has been shown to have direct and systemic effects on cancer pathogenesis and hosts anti-tumor immune response. Many studies have also shown that the host microbiota profile plays an essential role in the response to immunotherapy, especially immune checkpoint inhibitors. As such, modulating this microbial environment has offered a potential path to overcome the resistance to immune checkpoint inhibitors. In this review, we will talk about the role of microbiota in cancer pathogenesis and immune-system activity. We will also discuss preclinical and clinical studies that have increased our understanding about the roles and the mechanisms through which microbiota influences the response to treatment with immune checkpoint inhibitors.     

Metabolomic Profiling of Plasma from Melioidosis Patients Using UHPLC-QTOF MS Reveals Novel Biomarkers for Diagnosis

To identify potential biomarkers for improving diagnosis of melioidosis, we compared plasma metabolome profiles of melioidosis patients compared to patients with other bacteremia and controls without active infection, using ultra-high-performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry. Principal component analysis (PCA) showed that the metabolomic profiles of melioidosis patients are distinguishable from bacteremia patients and controls. Using multivariate and univariate analysis, 12 significant metabolites from four lipid classes, acylcarnitine (n = 6), lysophosphatidylethanolamine (LysoPE) (n = 3), sphingomyelins (SM) (n = 2) and phosphatidylcholine (PC) (n = 1), with significantly higher levels in melioidosis patients than bacteremia patients and controls, were identified. Ten of the 12 metabolites showed area-under-receiver operating characteristic curve (AUC) >0.80 when compared both between melioidosis and bacteremia patients, and between melioidosis patients and controls. SM(d18:2/16:0) possessed the largest AUC when compared, both between melioidosis and bacteremia patients (AUC 0.998, sensitivity 100% and specificity 91.7%), and between melioidosis patients and controls (AUC 1.000, sensitivity 96.7% and specificity 100%). Our results indicate that metabolome profiling might serve as a promising approach for diagnosis of melioidosis using patient plasma, with SM(d18:2/16:0) representing a potential biomarker. Since the 12 metabolites were related to various pathways for energy and lipid metabolism, further studies may reveal their possible role in the pathogenesis and host response in melioidosis.