Primjene teorije grafova: topologijski modeli za predvi|anje CDK-1 inhibicijske aktivnosti aloizina

Relationship between the topological indices and cyclin-dependent kinase-1 (CDK-1/cyclin B) inhibitory activity of 6-phenyl[5H]pyrrolo[2,3-b]pyrazines (aloisines) was investigated. Three topological indices – the Wiener Index, a distance-based topological descriptor, the Zagreb group parameter, an adjacency based topological descriptor, and the eccentric connectivity index, an adjacency-cum-distance based topological descriptor were used in the study. A data set comprising 51 analogues of aloisine was selected for the present study. Values of the Wiener index, the Zagreb group parameter and the eccentric connectivity index for each of the 51 analogues included in the data set were computed using an in-house computer program. Resultant data was analyzed and suitable models were developed after identification of active ranges. A biological activity was then assigned to each compound using these models, which was then compared with the reported CDK-1 inhibitory activity. Accuracy of prediction using these models was found to vary from a minimum of ≈82 % to a maximum of 84 %. .Istraživan je odnos izmđ|u topologijskih indeksa i CDK-1 inhibicijske aktivnosti 5-fenil[5H]pirolo[2,3-b]- pirazina (aloizina). Upotrebljena su tri topologijska indeksa: Wienerov indeks, zagrebački indeks i ekscentrični indeks povezanosti, koji su izračunani za 51 aloizin. Dobiveni modeli predviđaju inhibijsku aktivnosti aloizina s točnošću od 82–84 %

Primjene teorije grafova: topologijski modeli za predvi|anje CDK-1 inhibicijske aktivnosti aloizina

Relationship between the topological indices and cyclin-dependent kinase-1 (CDK-1/cyclin B) inhibitory activity of 6-phenyl[5H]pyrrolo[2,3-b]pyrazines (aloisines) was investigated. Three topological indices – the Wiener Index, a distance-based topological descriptor, the Zagreb group parameter, an adjacency based topological descriptor, and the eccentric connectivity index, an adjacency-cum-distance based topological descriptor were used in the study. A data set comprising 51 analogues of aloisine was selected for the present study. Values of the Wiener index, the Zagreb group parameter and the eccentric connectivity index for each of the 51 analogues included in the data set were computed using an in-house computer program. Resultant data was analyzed and suitable models were developed after identification of active ranges. A biological activity was then assigned to each compound using these models, which was then compared with the reported CDK-1 inhibitory activity. Accuracy of prediction using these models was found to vary from a minimum of ≈82 % to a maximum of 84 %. .Istraživan je odnos izmđ|u topologijskih indeksa i CDK-1 inhibicijske aktivnosti 5-fenil[5H]pirolo[2,3-b]- pirazina (aloizina). Upotrebljena su tri topologijska indeksa: Wienerov indeks, zagrebački indeks i ekscentrični indeks povezanosti, koji su izračunani za 51 aloizin. Dobiveni modeli predviđaju inhibijsku aktivnosti aloizina s točnošću od 82–84 %

Protection against Radiation Induced Performance Decrement in Mice

Recognising that there is lack of information on the effects of low-level ionizing radiations and the modifying role of radioprotectors, an attempt has been made in this study to explore the relationship between impairment of spatial learning and low level of radiation exposure. A radial arm maze was utilised to evaluate radiation-induced behavioural alterations and performance decrement in mice. Immediately after whole body exposure to gamma radiation (absorbed dose, I Gy) significant perturbations in the learned behaviour of the animals were observed. The regular control movement became irregular and the food consumption time was reduced appreciably (40 %). Recovery took place in four days. If diltiazem (7 mg/kg b.w.), a Ca/sup 2+/ channel blocker and a radioprotector, was administered i.p. 20-30 min prior to irradiation, radiation-induced behavioural abnormalities were reduced. Mechanisms underlying protection by diltiazem against radiation-induced performance decrement observed in the present study need to be investigated

A national qualitative investigation of the impact of service change on doctors' training during Covid-19

BACKGROUND: The Covid-19 crisis sparked service reconfigurations in healthcare systems worldwide. With postgraduate medical education sitting within these systems, service reconfigurations substantially impact trainees and their training environment. This study aims to provide an in-depth qualitative understanding of the impact of service reconfiguration on doctors' training during the pandemic, identifying opportunities for the future as well as factors that pose risks to education and training and how these might be mitigated. METHODS: Qualitative parallel multi-centre case studies examined three Trusts/Health Boards in two countries in the United Kingdom. Data were collected from online focus groups and interviews with trainees and supervisors using semi-structured interview guides (September to December 2020). A socio-cultural model of workplace learning, the expansive-restrictive continuum, informed data gathering, analysis of focus groups and coding. RESULTS: Sixty-six doctors participated, representing 25 specialties/subspecialties. Thirty-four participants were male, 26 were supervisors, 17 were specialty trainees and 23 were foundation doctors. Four themes described the impact of pandemic-related service reconfigurations on training: (1) Development of skills and job design, (2) Supervision and assessments, (3) Teamwork and communication, and (4) Workload and wellbeing. Service changes were found to both facilitate and hinder education and training, varying across sites, specialties, and trainees' grades. Trainees' jobs were redesigned extensively, and many trainees were redeployed to specialties requiring extra workforce during the pandemic. CONCLUSIONS: The rapid and unplanned service reconfigurations during the pandemic caused unique challenges and opportunities to doctors' training. This impaired trainees' development in their specialty of interest, but also presented new opportunities such as cross-boundary working and networking

Deriving a preference-based measure for cancer using the EORTC QLQ-C30 : a confirmatory versus exploratory approach

Background: To derive preference-based measures from various condition-specific descriptive health-related quality of life (HRQOL) measures. A general 2-stage method is evolved: 1) an item from each domain of the HRQOL measure is selected to form a health state classification system (HSCS); 2) a sample of health states is valued and an algorithm derived for estimating the utility of all possible health states. The aim of this analysis was to determine whether confirmatory or exploratory factor analysis (CFA, EFA) should be used to derive a cancer-specific utility measure from the EORTC QLQ-C30. Methods: Data were collected with the QLQ-C30v3 from 356 patients receiving palliative radiotherapy for recurrent or metastatic cancer (various primary sites). The dimensional structure of the QLQ-C30 was tested with EFA and CFA, the latter based on a conceptual model (the established domain structure of the QLQ-C30: physical, role, emotional, social and cognitive functioning, plus several symptoms) and clinical considerations (views of both patients and clinicians about issues relevant to HRQOL in cancer). The dimensions determined by each method were then subjected to item response theory, including Rasch analysis. Results: CFA results generally supported the proposed conceptual model, with residual correlations requiring only minor adjustments (namely, introduction of two cross-loadings) to improve model fit (increment χ2(2) = 77.78, p 75% observation at lowest score), 6 exhibited misfit to the Rasch model (fit residual > 2.5), none exhibited disordered item response thresholds, 4 exhibited DIF by gender or cancer site. Upon inspection of the remaining items, three were considered relatively less clinically important than the remaining nine. Conclusions: CFA appears more appropriate than EFA, given the well-established structure of the QLQ-C30 and its clinical relevance. Further, the confirmatory approach produced more interpretable results than the exploratory approach. Other aspects of the general method remain largely the same. The revised method will be applied to a large number of data sets as part of the international and interdisciplinary project to develop a multi-attribute utility instrument for cancer (MAUCa)

My mind is made up: Cancer concern and women’s preferences for contralateral prophylactic mastectomy

© 2019 John Wiley & Sons Ltd The fear of cancer recurrence is cited as a motivator of women's preferences between routine monitoring and contralateral prophylactic mastectomy (CPM) as methods of managing ongoing breast cancer risk. We conducted a discrete choice experiment among a general community sample of women who completed 12 hypothetical choices between routine monitoring and CPM described by aspects of treatment efficacy, safety, cost and involvement in decision-making. Respondents also completed a modified cancer worry question to assess cancer concern. Approximately 57.5% of 464 women always chose one option, typically routine monitoring. The majority (71.5%) reported being concerned about cancer recurrence when completing choice tasks. Latent class analysis identified three groups: preferred routine monitoring; preferred CPM; and “traders” (willing to swap between options). Among traders, women were less likely to choose an option associated with higher risk of recurrence. Women were more likely to choose options associated with less-intrusive monitoring methods and where they were involved in decision-making. Women concerned about cancer recurrence were more likely to choose CPM over monitoring. This study shows that women's preferences about how to manage breast cancer recurrence risk reflect the importance of the associated health effects, experience of care and attitudes to cancer recurrence

Receptive field vectors of genetically-identified retinal ganglion cells reveal cell-type-dependent visual functions

Sensory stimuli are encoded by diverse kinds of neurons but the identities of the recorded neurons that are studied are often unknown. We explored in detail the firing patterns of eight previously defined genetically-identified retinal ganglion cell (RGC) types from a single transgenic mouse line. We first introduce a new technique of deriving receptive field vectors (RFVs) which utilises a modified form of mutual information ("Quadratic Mutual Information"). We analysed the firing patterns of RGCs during presentation of short duration (~10 second) complex visual scenes (natural movies). We probed the high dimensional space formed by the visual input for a much smaller dimensional subspace of RFVs that give the most information about the response of each cell. The new technique is very efficient and fast and the derivation of novel types of RFVs formed by the natural scene visual input was possible even with limited numbers of spikes per cell. This approach enabled us to estimate the 'visual memory' of each cell type and the corresponding receptive field area by calculating Mutual Information as a function of the number of frames and radius. Finally, we made predictions of biologically relevant functions based on the RFVs of each cell type. RGC class analysis was complemented with results for the cells' response to simple visual input in the form of black and white spot stimulation, and their classification on several key physiological metrics. Thus RFVs lead to predictions of biological roles based on limited data and facilitate analysis of sensory-evoked spiking data from defined cell types

The impact of service change on doctors' training (GMC 822)

The aim of this research is to gain a deeper understanding about the direct and indirect impacts of service change on doctors’ training: to understand if specific types of service change pose a risk to the training experience, and to gain insights into the contextual influences that undermine or enhance the education of doctors during service change

A systematic review of scabies transmission models and data to evaluate the cost-effectiveness of scabies interventions

© 2019 van der Linden et al. Background: Scabies is a common dermatological condition, affecting more than 130 million people at any time. To evaluate and/or predict the effectiveness and cost-effectiveness of scabies interventions, disease transmission modelling can be used. Objective: To review published scabies models and data to inform the design of a comprehensive scabies transmission modelling framework to evaluate the cost-effectiveness of scabies interventions. Methods: Systematic literature search in PubMed, Medline, Embase, CINAHL, and the Cochrane Library identified scabies studies published since the year 2000. Selected papers included modelling studies and studies on the life cycle of scabies mites, patient quality of life and resource use. Reference lists of reviews were used to identify any papers missed through the search strategy. Strengths and limitations of identified scabies models were evaluated and used to design a modelling framework. Potential model inputs were identified and discussed. Findings: Four scabies models were published: a Markov decision tree, two compartmental models, and an agent-based, network-dependent Monte Carlo model. None of the models specifically addressed crusted scabies, which is associated with high morbidity, mortality, and increased transmission. There is a lack of reliable, comprehensive information about scabies biology and the impact this disease has on patients and society. Discussion: Clinicians and health economists working in the field of scabies are encouraged to use the current review to inform disease transmission modelling and economic evaluations on interventions against scabies