PALLIATION AND LIFE QUALITY IN LUNG-CANCER - HOW GOOD ARE CLINICIAN AT JUDGING TREATMENT OUTCOME

A recent trial by the MRC Lung Cancer Working Party used physician assessments to compare two palliative schedules of radiotherapy in lung cancer. A prospective study has been undertaken on a subset of these trial patients to see how physician assessments of symptomatic relief and general condition correlate with patient perception of therapeutic response. In 40 patients followed up monthly from presentation until close to death, good agreement was found between doctors and patients on change in specific physical symptoms and overall physical condition. Doctors were poor judges of life quality at presentation but appeared able to identify relative improvement or deterioration in overall quality of life. In conclusion, physician assessments may constitute valid end-points for radiotherapy trials comparing palliative schedules in lung cance

Kinetics and Product Branching Ratio Study of the CH3O2 Self-Reaction in the Highly Instrumented Reactor for Atmospheric Chemistry

The fluorescence assay by gas expansion (FAGE) method for the measurement of the methyl peroxy radical (CH3O2) using the conversion of CH3O2 into methoxy radicals (CH3O) by excess NO, followed by the detection of CH3O, has been used to study the kinetics of the self-reaction of CH3O2. Fourier transform infrared (FTIR) spectroscopy has been employed to determine the products methanol and formaldehyde of the self-reaction. The kinetics and product studies were performed in the Highly Instrumented Reactor for Atmospheric Chemistry (HIRAC) in the temperature range 268–344 K at 1000 mbar of air. The product measurements were used to determine the branching ratio of the reaction channel forming methoxy radicals, rCH3O. A value of 0.34 ± 0.05 (errors at 2σ level) was determined for rCH3O at 295 K. The temperature dependence of rCH3O can be parametrized as rCH3O = 1/{1 + [exp(600 ± 85)/T]/(3.9 ± 1.1)}. An overall rate coefficient of the self-reaction of (2.0 ± 0.9) × 10–13 cm3 molecule–1 s–1 at 295 K was obtained by the kinetic analysis of the observed second-order decays of CH3O2. The temperature dependence of the overall rate coefficient can be characterized by koverall = (9.1 ± 5.3) × 10–14 × exp((252 ± 174)/T) cm3 molecule–1 s–1. The found values of koverall in the range 268–344 K are ∼40% lower than the values calculated using the recommendations of the Jet Propulsion Laboratory and IUPAC, which are based on the previous studies, all of them utilizing time-resolved UV–absorption spectroscopy to monitor CH3O2. A modeling study using a complex chemical mechanism to describe the reaction system showed that unaccounted secondary chemistry involving Cl species increased the values of koverall in the previous studies using flash photolysis to initiate the chemistry. The overestimation of the koverall values by the kinetic studies using molecular modulation to generate CH3O2 can be rationalized by a combination of underestimated optical absorbance of CH3O2 and unaccounted CH3O2 losses to the walls of the reaction cells employed

Managing the complexity of doing it all : an exploratory study on students' experiences when trained stepwise in conducting consultations

Background: At most medical schools the components required to conduct a consultation, medical knowledge, communication, clinical reasoning and physical examination skills, are trained separately. Afterwards, all the knowledge and skills students acquired must be integrated into complete consultations, an art that lies at the heart of the medical profession. Inevitably, students experience conducting consultations as complex and challenging. Literature emphasizes the importance of three didactic course principles: moving from partial tasks to whole task learning, diminishing supervisors' support and gradually increasing students' responsibility. This study explores students' experiences of an integrated consultation course using these three didactic principles to support them in this difficult task. Methods: Six focus groups were conducted with 20 pre-clerkship and 19 clerkship students in total. Discussions were audiotaped, transcribed and analysed by Nvivo using the constant comparative strategy within a thematic analysis. Results: Conducting complete consultations motivated students in their learning process as future physician. Initially, students were very much focused on medical problem solving. Completing the whole task of a consultation obligated them to transfer their theoretical medical knowledge into applicable clinical knowledge on the spot. Furthermore, diminishing the support of a supervisor triggered students to reflect on their own actions but contrasted with their increased appreciation of critical feedback. Increasing students' responsibility stimulated their active learning but made some students feel overloaded. These students were anxious to miss patient information or not being able to take the right decisions or to answer patients' questions, which sometimes resulted in evasive coping techniques, such as talking faster to prevent the patient asking questions. Conclusion: The complex task of conducting complete consultations should be implemented early within medical curricula because students need time to organize their medical knowledge into applicable clinical knowledge. An integrated consultation course should comprise a step-by-step teaching strategy with a variety of supervisors' feedback modi, adapted to students' competence. Finally, students should be guided in formulating achievable standards to prevent them from feeling overloaded in practicing complete consultations with simulated or real patients

What is the impact of a national postgraduate medical specialist education reform on the daily clinical training 3.5 years after implementation? A questionnaire survey

<p>Abstract</p> <p>Background</p> <p>Many countries have recently reformed their postgraduate medical education (PGME). New pedagogic initiatives and blueprints have been introduced to improve quality and effectiveness of the education. Yet it is unknown whether these changes improved the daily clinical training. The purpose was to examine the impact of a national PGME reform on the daily clinical training practice.</p> <p>Methods</p> <p>The Danish reform included change of content and format of specialist education in line with outcome-based education using the CanMEDS framework. We performed a questionnaire survey among all hospital doctors in the North Denmark Region. The questionnaire included items on educational appraisal meetings, individual learning plans, incorporating training issues into work routines, supervision and feedback, and interpersonal acquaintance. Data were collected before start and 31/2 years later. Mean score values were compared, and response variables were analysed by multiple regression to explore the relation between the ratings and seniority, type of hospital, type of specialty, and effect of attendance to courses in learning and teaching among respondents.</p> <p>Results</p> <p>Response rates were 2105/2817 (75%) and 1888/3284 (58%), respectively. We found limited impact on clinical training practice and learning environment. Variances in ratings were hardly affected by type of hospital, whereas belonging to the laboratory specialities compared to other specialties was related to higher ratings concerning all aspects.</p> <p>Conclusions</p> <p>The impact on daily clinical training practice of a national PGME reform was limited after 31/2 years. Future initiatives must focus on changing the pedagogical competences of the doctors participating in daily clinical training and on implementation strategies for changing educational culture.</p

The need to promote behaviour change at the cultural level: one factor explaining the limited impact of the MEMA kwa Vijana adolescent sexual health intervention in rural Tanzania. A process evaluation

Background - Few of the many behavioral sexual health interventions in Africa have been rigorously evaluated. Where biological outcomes have been measured, improvements have rarely been found. One of the most rigorous trials was of the multi-component MEMA kwa Vijana adolescent sexual health programme, which showed improvements in knowledge and reported attitudes and behaviour, but none in biological outcomes. This paper attempts to explain these outcomes by reviewing the process evaluation findings, particularly in terms of contextual factors. Methods - A large-scale, primarily qualitative process evaluation based mainly on participant observation identified the principal contextual barriers and facilitators of behavioural change. Results - The contextual barriers involved four interrelated socio-structural factors: culture (i.e. shared practices and systems of belief), economic circumstances, social status, and gender. At an individual level they appeared to operate through the constructs of the theories underlying MEMA kwa Vijana - Social Cognitive Theory and the Theory of Reasoned Action – but the intervention was unable to substantially modify these individual-level constructs, apart from knowledge. Conclusion - The process evaluation suggests that one important reason for this failure is that the intervention did not operate sufficiently at a structural level, particularly in regard to culture. Recently most structural interventions have focused on gender or/and economics. Complementing these with a cultural approach could address the belief systems that justify and perpetuate gender and economic inequalities, as well as other barriers to behaviour change

Variational Methods for Biomolecular Modeling

Structure, function and dynamics of many biomolecular systems can be characterized by the energetic variational principle and the corresponding systems of partial differential equations (PDEs). This principle allows us to focus on the identification of essential energetic components, the optimal parametrization of energies, and the efficient computational implementation of energy variation or minimization. Given the fact that complex biomolecular systems are structurally non-uniform and their interactions occur through contact interfaces, their free energies are associated with various interfaces as well, such as solute-solvent interface, molecular binding interface, lipid domain interface, and membrane surfaces. This fact motivates the inclusion of interface geometry, particular its curvatures, to the parametrization of free energies. Applications of such interface geometry based energetic variational principles are illustrated through three concrete topics: the multiscale modeling of biomolecular electrostatics and solvation that includes the curvature energy of the molecular surface, the formation of microdomains on lipid membrane due to the geometric and molecular mechanics at the lipid interface, and the mean curvature driven protein localization on membrane surfaces. By further implicitly representing the interface using a phase field function over the entire domain, one can simulate the dynamics of the interface and the corresponding energy variation by evolving the phase field function, achieving significant reduction of the number of degrees of freedom and computational complexity. Strategies for improving the efficiency of computational implementations and for extending applications to coarse-graining or multiscale molecular simulations are outlined.Comment: 36 page

Proapoptotic genes BAX and CD40L are predictors of survival in transitional cell carcinoma of the bladder

The purpose of the study was to investigate the effects of expression of a range of genes involved in apoptosis on outcome in bladder cancer. Immunohistochemistry was used to examine expression of BCL2, BAX, P53, CD40 and CD40L in archival tissues of patients included in various treatment trials for transitional cell carcinoma (TCC) of the bladder. Data were collected on 94 patients who first presented with either invasive or superficial bladder cancer. Median follow-up for alive patients was 83 months (m) (range 12-195 m). Median survival was 80 m (95% CI=56-128 m). Median survivals for the various markers were as follows: BAX-positive patients 110 m vs BAX-negative patients 18 m (P=0.0002); CD40L-positive patients 95 m vs CD40L-negative patients 45 m (P=0.04); BCL2-positive patients 44 m and BCL2-negative patients 74 m, (P=0.64); CD40-positive patients 110 m and CD40 negative patients 45 m (P=0.12); and P53 positive patients 80 m and P53 negative patients 45 m (P=0.58). In conclusion, it was seen that overexpressions of BAX and CD40L are prognostic of better survival in TCC of the bladder. Our results also raise the possibility of the future development of CD40- and CD40 ligand-based immunotherapy for bladder cancer. This study links proapoptotic and antiapoptotic markers to overall survival

Maternal feeding practices and fussy eating in toddlerhood: A discordant twin analysis

Background: Parental feeding practices are thought to play a causal role in shaping a child's fussiness; however, a child-responsive model suggests that feeding practices may develop in response to a child's emerging appetitive characteristics. We used a novel twin study design to test the hypothesis that mothers vary their feeding practices for twin children who differ in their 'food fussiness', in support of a child-responsive model. Methods: Participants were mothers and their 16 month old twin children (n=2026) from Gemini, a British twin birth cohort of children born in 2007. Standardized psychometric measures of maternal 'pressure to eat', 'restriction' and 'instrumental feeding', as well as child 'food fussiness', were completed by mothers. Within-family analyses examined if twin-pair differences in 'food fussiness' were associated with differences in feeding practices using linear regression models. In a subset of twins (n=247 pairs) who were the most discordant (highest quartile) on 'food fussiness' (difference score≥.50), Paired Samples T-test were used to explore the magnitude of differences in feeding practices between twins. Between-family analyses used Complex Samples General Linear Models to examine associations between feeding practices and 'food fussiness'. Results: Within-pair differences in 'food fussiness' were associated with differential 'pressure to eat' and 'instrumental feeding' (ps<.001), but not with 'restriction'. In the subset of twins most discordant on 'food fussiness', mothers used more pressure (p<.001) and food rewards (p<.05) with the fussier twin. Between-family analyses indicated that 'pressure to eat' and 'instrumental feeding' were positively associated with 'food fussiness', while 'restriction' was negatively associated with 'food fussiness' (ps<.001). Conclusions: Mothers appear to subtly adjust their feeding practices according to their perceptions of their toddler's emerging fussy eating behavior. Specifically, the fussier toddler is pressured more than their less fussy co-twin, and is more likely to be offered food rewards. Guiding parents on how to respond to fussy eating may be an important aspect of promoting feeding practices that encourage food acceptance

Septoria-like pathogens causing leaf and fruit spot of pistachio

Several species of Septoria are associated with leaf and fruit spot of pistachio (Pistacia vera), though their identity has always been confused, making identification problematic. The present study elucidates the taxonomy of the Septoria spp. associated with pistachio, and distinguishes four species associated with this host genus. Partial nucleotide sequence data for five gene loci, ITS, LSU, EF-1a, RPB2 and Btub were generated for a subset of isolates. Cylindroseptoria pistaciae, which is associated with leaf spots of Pistacia lentiscus in Spain, is characterised by pycnidial conidiomata that give rise to cylindrical, aseptate conidia. Two species of Septoria s. str. are also recognised on pistachio, S. pistaciarum, and S. pistaciae. The latter is part of the S. protearum species complex, and appears to be a wide host range pathogen occurring on hosts in several different plant families. Septoria pistacina, a major pathogen of pistachio in Turkey, is shown to belong to Pseudocercospora, and not Septoria as earlier suspected. Other than for its pycnidial conidiomata, it is a typical species of Pseudocercospora based on its smooth, pigmented conidiogenous cells and septate conidia. This phenomenon has also been observed in Pallidocercospora, and seriously questions the value of conidiomatal structure at generic level, which has traditionally been used to separate hyphomycetous from coelomycetous ascomycetes. Other than DNA barcodes to facilitate the molecular identification of these taxa occurring on pistachio, a key is also provided to distinguish species based on morphology

Effect of phosphate and temperature on force exerted by white muscle fibres from dogfish.

Effects of Pi (inorganic phosphate) are relevant to the in vivo function of muscle because Pi is one of the products of ATP hydrolysis by actomyosin and by the sarcoplasmic reticulum Ca pump. We have measured the Pi sensitivity of force produced by permeabilized muscle fibres from dogfish (Scyliorhinus canicula) and rabbit. The activation conditions for dogfish fibres were crucial: fibres activated from the relaxed state at 5, 12, and 20°C were sensitive to Pi, whereas fibres activated from rigor at 12°C were insensitive to Pi in the range 5-25 mmol l. Rabbit fibres activated from rigor were sensitive to Pi. Pi sensitivity of force produced by dogfish fibres activated from the relaxed state was greater below normal body temperature (12°C for dogfish) in agreement with what is known for other species. The force-temperature relationship for dogfish fibres (intact and permeabilized fibres activated from relaxed) showed that at 12°C, normal body temperature, the force was near to its maximum value