In-training assessment using direct observation of single-patient encounters: a literature review

We reviewed the literature on instruments for work-based assessment in single clinical encounters, such as the mini-clinical evaluation exercise (mini-CEX), and examined differences between these instruments in characteristics and feasibility, reliability, validity and educational effect. A PubMed search of the literature published before 8 January 2009 yielded 39 articles dealing with 18 different assessment instruments. One researcher extracted data on the characteristics of the instruments and two researchers extracted data on feasibility, reliability, validity and educational effect. Instruments are predominantly formative. Feasibility is generally deemed good and assessor training occurs sparsely but is considered crucial for successful implementation. Acceptable reliability can be achieved with 10 encounters. The validity of many instruments is not investigated, but the validity of the mini-CEX and the ‘clinical evaluation exercise’ is supported by strong and significant correlations with other valid assessment instruments. The evidence from the few studies on educational effects is not very convincing. The reports on clinical assessment instruments for single work-based encounters are generally positive, but supporting evidence is sparse. Feasibility of instruments seems to be good and reliability requires a minimum of 10 encounters, but no clear conclusions emerge on other aspects. Studies on assessor and learner training and studies examining effects beyond ‘happiness data’ are badly needed

Host-guest and guest-guest interactions between xylene isomers confined in the MIL-47(V) pore system

The porous MIL-47 material shows a selective adsorption behavior for para-, ortho-, and meta-isomers of xylenes, making the material a serious candidate for separation applications. The origin of the selectivity lies in the differences in interactions (energetic) and confining (entropic). This paper investigates the xylene-framework interactions and the xylene-xylene interactions with quantum mechanical calculations, using a dispersion-corrected density functional and periodic boundary conditions to describe the crystal. First, the strength and geometrical characteristics of the optimal xylene-xylene interactions are quantified by studying the pure and mixed pairs in gas phase. An extended set of initial structures is created and optimized to sample as many relative orientations and distances as possible. Next, the pairs are brought in the pores of MIL-47. The interaction with the terephthalic linkers and other xylenes increases the stacking energy in gas phase (-31.7 kJ/mol per pair) by roughly a factor four in the fully loaded state (-58.3 kJ/mol per xylene). Our decomposition of the adsorption energy shows various trends in the contributing xylene-xylene interactions. The absence of a significant difference in energetics between the isomers indicates that entropic effects must be mainly responsible for the separation behavior

Broadening Exposure to Socio-Political Opinions via a Pushy Smart Home Device

Motivated by the effects of the filter bubble and echo chamber phenomena on social media, we developed a smart home device, Spkr, that unpredictably “pushes” socio-political discussion topics into the home. The device utilised trending Twitter discussions, categorised by their socio-political alignment, to present people with a purposefully assorted range of viewpoints. We deployed Spkr in 10 homes for 28 days with a diverse range of participants and interviewed them about their experiences. Our results show that Spkr presents a novel means of combating selective exposure to socio-political issues, providing participants with identifiably diverse viewpoints. Moreover, Spkr acted as a conversational prompt for discussion within the home, initiating collective processes and engaging those who would not often be involved in political discussions. We demonstrate how smart home assistants can be used as a catalyst for provocation by altering and pluralising political discussions within households

Systems Biology Approaches Reveal a Specific Interferon-Inducible Signature in HTLV-1 Associated Myelopathy

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that persists lifelong in the host. In ∼4% of infected people, HTLV-1 causes a chronic disabling neuroinflammatory disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The pathogenesis of HAM/TSP is unknown and treatment remains ineffective. We used gene expression microarrays followed by flow cytometric and functional assays to investigate global changes in blood transcriptional profiles of HTLV-1-infected and seronegative individuals. We found that perturbations of the p53 signaling pathway were a hallmark of HTLV-1 infection. In contrast, a subset of interferon (IFN)-stimulated genes was over-expressed in patients with HAM/TSP but not in asymptomatic HTLV-1 carriers or patients with the clinically similar disease multiple sclerosis. The IFN-inducible signature was present in all circulating leukocytes and its intensity correlated with the clinical severity of HAM/TSP. Leukocytes from patients with HAM/TSP were primed to respond strongly to stimulation with exogenous IFN. However, while type I IFN suppressed expression of the HTLV-1 structural protein Gag it failed to suppress the highly immunogenic viral transcriptional transactivator Tax. We conclude that over-expression of a subset of IFN-stimulated genes in chronic HTLV-1 infection does not constitute an efficient host response but instead contributes to the development of HAM/TSP

The Acclimation of European Sea Bass (Dicentrarchus labrax) to Temperature: Behavioural and Neurochemical Responses

Studies on fish behavioural and neurophysiological responses to water temperature change may contribute to an improved understanding of the ecological consequences of global warming. We investigated behavioural and neurochemical responses to water temperature in European sea bass (Dicentrarchus labrax) acclimated to three temperatures (18, 22 and 28°C). After 21 d of acclimation, three groups of 25 fish each were exposed to four behavioural challenges (foraging, olfactory, aversive and mirror tests). The expression of choline acetyltransferase (ChAT) was then analysed by Western blotting in CNS homogenates (from a subset of the same fish) as a marker for cholinergic system activity. In both foraging and olfactory tests, fish acclimated to 28°C exhibited significantly higher arousal responses than fish acclimated to lower temperatures. All specimens showed fright behaviour in the aversive test, but the latency of the escape response was significantly less in the fish at 28°C. Finally, the highest mirror responsiveness was exhibited by the fish acclimated to 22°C. As in the case of cholinergic neurotransmission, significantly higher ChAT levels were detected in the telencephalon, diencephalon, cerebellum and spinal cord of fish acclimated to 22 or 28°C in comparison with those maintained at 18°C. Lower ChAT levels were detected in the mesencephalon (optic tectum) at 22 and 28°C than at 18°C. These data indicate that neuronal functions are affected by water temperature. Increases or decreases in ChAT expression can be related to the functional modulation of brain and spinal cord centres involved in behavioural responses to temperature change. Overall, the results of this study suggest that the environmental temperature level influences behaviour and CNS neurochemistry in the European sea bass.Studies on fish behavioural and neurophysiological responses to water temperature change may contribute to an improved understanding of the ecological consequences of global warming. We investigated behavioural and neurochemical responses to water temperature in European sea bass (Dicentrarchus labrax) acclimated to three temperatures (18, 22 and 28 degrees C). After 21d of acclimation, three groups of 25 fish each were exposed to four behavioural challenges (foraging, olfactory, aversive and mirror tests). The expression of choline acetyltransferase (ChAT) was then analysed by Western blotting in CNS homogenates (from a subset of the same fish) as a marker for cholinergic system activity. In both foraging and olfactory tests, fish acclimated to 28 degrees C exhibited significantly higher arousal responses than fish acclimated to lower temperatures. All specimens showed fright behaviour in the aversive test, but the latency of the escape response was significantly less in the fish at 28 degrees C. Finally, the highest mirror responsiveness was exhibited by the fish acclimated to 22 degrees C. As in the case of cholinergic neurotransmission, significantly higher ChAT levels were detected in the telencephalon, diencephalon, cerebellum and spinal cord of fish acclimated to 22 or 28 degrees C in comparison with those maintained at 18 degrees C. Lower ChAT levels were detected in the mesencephalon (optic tectum) at 22 and 28 degrees C than at 18 degrees C. These data indicate that neuronal functions are affected by water temperature. Increases or decreases in ChAT expression can be related to the functional modulation of brain and spinal cord centres involved in behavioural responses to temperature change. Overall, the results of this study suggest that the environmental temperature level influences behaviour and CNS neurochemistry in the European sea bass

Cisplatin resistance in non-small cell lung cancer cells is associated with an abrogation of cisplatin-induced G2/M cell cycle arrest

The efficacy of cisplatin-based chemotherapy in cancer is limited by the occurrence of innate and acquired drug resistance. In order to better understand the mechanisms underlying acquired cisplatin resistance, we have compared the adenocarcinoma-derived non-small cell lung cancer (NSCLC) cell line A549 and its cisplatin-resistant sub-line A549rCDDP2000 with regard to cisplatin resistance mechanisms including cellular platinum accumulation, DNA-adduct formation, cell cycle alterations, apoptosis induction and activation of key players of DNA damage response. In A549rCDDP2000 cells, a cisplatin-induced G2/M cell cycle arrest was lacking and apoptosis was reduced compared to A549 cells, although equitoxic cisplatin concentrations resulted in comparable platinum-DNA adduct levels. These differences were accompanied by changes in the expression of proteins involved in DNA damage response. In A549 cells, cisplatin exposure led to a significantly higher expression of genes coding for proteins mediating G2/M arrest and apoptosis (mouse double minute 2 homolog (MDM2), xeroderma pigmentosum complementation group C (XPC), stress inducible protein (SIP) and p21) compared to resistant cells. This was underlined by significantly higher protein levels of phosphorylated Ataxia telangiectasia mutated (pAtm) and p53 in A549 cells compared to their respective untreated control. The results were compiled in a preliminary model of resistance-associated signaling alterations. In conclusion, these findings suggest that acquired resistance of NSCLC cells against cisplatin is the consequence of altered signaling leading to reduced G2/M cell cycle arrest and apoptosis

From risk assessment to regulation

Pesticides are among the most heavily regulated chemicals, not unlike pharmaceuticals. Human health risks from exposure to pesticides are assessed by integrating information on the hazardous characteristics of the pesticide, usually gained from experimental studies, with data on human exposure. This process allows the setting of health-based guidance values for pesticide operators, bystanders, residents, and consumers who may be exposed through residues in the diet. Pesticide regulation is currently undergoing a paradigm shift with a move away from traditional toxicity assessment of individual substances in experimental animals toward integration of novel assessment methods which allow mechanism-based assessment of multiple exposures