Tools for Assessing Outcomes in Studies of Chronic Cough: CHEST Guideline and Expert Panel Report

BACKGROUND: Since the publication of the 2006 American College of Chest Physicians (CHEST) cough guidelines, a variety of tools has been developed or further refined for assessing cough. The purpose of the present committee was to evaluate instruments used by investigators performing clinical research on chronic cough. The specific aims were to (1) assess the performance of tools designed to measure cough frequency, severity, and impact in adults, adolescents, and children with chronic cough and (2) make recommendations or suggestions related to these findings.

METHODS: By following the CHEST methodologic guidelines, the CHEST Expert Cough Panel based its recommendations and suggestions on a recently published comparative effectiveness review commissioned by the US Agency for Healthcare Research and Quality, a corresponding summary published in CHEST, and an updated systematic review through November 2013. Recommendations or suggestions based on these data were discussed, graded, and voted on during a meeting of the Expert Cough Panel.

RESULTS: We recommend for adults, adolescents (≥ 14 years of age), and children complaining of chronic cough that validated and reliable health-related quality-of-life (QoL) questionnaires be used as the measurement of choice to assess the impact of cough, such as the Leicester Cough Questionnaire and the Cough-Specific Quality-of-Life Questionnaire in adult and adolescent patients and the Parent Cough-Specific Quality of Life Questionnaire in children. We recommend acoustic cough counting to assess cough frequency but not cough severity. Limited data exist regarding the performance of visual analog scales, numeric rating scales, and tussigenic challenges.

CONCLUSIONS: Validated and reliable cough-specific health-related QoL questionnaires are recommended as the measurement of choice to assess the impact of cough on patients. How they compare is yet to be determined. When used, the reporting of cough severity by visual analog or numeric rating scales should be standardized. Previously validated QoL questionnaires or other cough assessments should not be modified unless the new version has been shown to be reliable and valid. Finally, in research settings, tussigenic challenges play a role in understanding mechanisms of cough.

Family Economic Vulnerability & the Great Recession: An Analysis of the First two Waves of the Growing Up in Ireland Study

In this paper we make use of the first and second waves of the 2008 and 1998 cohorts of the Growing Up in Ireland study, to develop a multidimensional and dynamic approach to understanding the impact on families and children in Ireland of the Great Recession. Economic vulnerability is operationalised as involving a distinctive risk profile in relation to relative income, household joblessness and economic stress. We find that the recession was associated with a significant increase in levels of economic vulnerability and changing risk profiles involving a more prominent role for economic stress for both the 2008 and 1998 cohorts. The factors affecting vulnerability outcomes were broadly similar for both cohorts. Persistent economic vulnerability was significantly associated with lone parenthood, particularly for those with more than one child, lower levels of Primary Care Giver (PCG) education and to a lesser extent younger age of PCG at child’s birth, number of children and a parent leaving or dying. Similar factors were associated with transient vulnerability in the first wave but the magnitude of the effects was significantly weaker particularly in relation to lone parenthood and level of education of the PCG. For entry into vulnerability the impact of these factors was again substantially weaker than for persistent and transient vulnerability indicating a significantly greater degree of socio-economic heterogeneity among the group that became vulnerable during the recession. The findings raise policy and political problems that go beyond those associated with catering for groups that have tended to be characterized by high dependence on social welfare.

Prescribing for children and adolescents in mental health

The level of psychiatric prescribing in children and adolescents is increasing; however, rates of adherence in this group of patients range from only 34–54%. The possible consequences of untreated psychiatric problems include longer duration of the illness, increased severity of symptoms, higher relapse rates, greater risk of suicidal behaviour, academic difficulties and increased family conflict. Prescribers are often faced with difficulty if the parent or carer is not in agreement with the use of medication. This parental disagreement has implications for medication concordance and the relationship between clinicians, young people and their families. For prescribers, understanding parental and young people's attitudes towards medication and their experiences of mental health services is central to patient-centred care.

A cluster randomised controlled trial and process evaluation of the early years DELTA parenting programme

This paper reports the results from a cluster randomised controlled trial (RCT) and process evaluation of the Early Years DELTA Parenting Programme; a six-week, group based intervention. The evaluation was part funded by DELTA and involved 23 primary schools and 334 parents. Results showed that intervention parents reported increased parental self-efficacy in relation to: knowledge of their child’s development and needs; self-acceptance as a good parent, and; disciplining and setting boundaries. No change was observed in the remaining outcome areas. Parent interviews indicated a high level of programme satisfaction and the main benefits reflected the outcomes measured by the RCT. This small, robust evaluation is commensurate with other similar research demonstrating the effectiveness and reach of short-term, group-based parenting programmes.

Optical Spectroscopy of Unbound Asteroid Pairs

The recently discovered unbound asteroid pairs have been suggested to be the result of the decoupling of binary asteroids formed either through collision processes or, more likely, rotational fission of a rubble-pile asteroid after spin-up (Vokrouhlicky et al. 2008, AJ 136, 280; Pravec et al., 2010, Nature, 466, 1085). Much of the evidence for linkage of the asteroids in each pair relies solely on the backwards integrations of their orbits. We report new results from our continuing spectroscopic survey of the unbound asteroid pairs, including the youngest known pair, (6070) Rhineland - (54827) 2001 NQ8. The survey goal is to determine whether the asteroids in each unbound pair have similar spectra and therefore composition, expected if they have formed from a common parent body. Low-resolution spectroscopy covering the range 0.4-0.95 microns was conducted using the 3.6m ESO NTT+EFOSC2 during 2011-2012 and the 4.2m WHT+ACAM. We have attempted to maintain a high level of consistency between the observations of the components in each pair to ensure that differences in the asteroid spectra are not the result of the observing method or data reduction, but purely caused by compositional differences. Our WHT data indicates that the asteroids of unbound pair 17198 - 229056 exhibit different spectra and have been assigned different taxonomies, A and R respectively. Initial analysis of our data from the NTT suggests that the asteroids in unbound pairs 6070 - 54827 and 38707 - 32957 are likely silicate-dominated asteroids. The components of pair 23998 - 205383 are potentially X-type asteroids. We present final taxonomic classifications and the likelihood of spectral similarity in each pair.

A collision in 2009 as the origin of the debris trail of asteroid P/2010A2

The peculiar object P/2010A2 was discovered in January 2010 and given a cometary designation because of the presence of a trail of material, although there was no central condensation or coma. The appearance of this object, in an asteroidal orbit (small eccentricity and inclination) in the inner main asteroid belt attracted attention as a potential new member of the recently recognized class of main-belt comets. If confirmed, this new object would expand the range in heliocentric distance over which main-belt comets are found. Here we report observations of P/2010A2 by the Rosetta spacecraft. We conclude that the trail arose from a single event, rather than a period of cometary activity, in agreement with independent results. The trail is made up of relatively large particles of millimetre to centimetre size that remain close to the parent asteroid. The shape of the trail can be explained by an initial impact ejecting large clumps of debris that disintegrated and dispersed almost immediately. We determine that this was an asteroid collision that occurred around 10 February 2009.

Molecular pedigree reconstruction and estimation of evolutionary parameters in a wild Atlantic salmon river system with incomplete sampling: a power analysis

Background: Pedigree reconstruction using genetic analysis provides a useful means to estimate fundamental population biology parameters relating to population demography, trait heritability and individual fitness when combined with other sources of data. However, there remain limitations to pedigree reconstruction in wild populations, particularly in systems where parent-offspring relationships cannot be directly observed, there is incomplete sampling of individuals, or molecular parentage inference relies on low quality DNA from archived material. While much can still be inferred from incomplete or sparse pedigrees, it is crucial to evaluate the quality and power of available genetic information a priori to testing specific biological hypotheses. Here, we used microsatellite markers to reconstruct a multi-generation pedigree of wild Atlantic salmon (Salmo salar L.) using archived scale samples collected with a total trapping system within a river over a 10 year period. Using a simulation-based approach, we determined the optimal microsatellite marker number for accurate parentage assignment, and evaluated the power of the resulting partial pedigree to investigate important evolutionary and quantitative genetic characteristics of salmon in the system.

Results: We show that at least 20 microsatellites (ave. 12 alleles/locus) are required to maximise parentage assignment and to improve the power to estimate reproductive success and heritability in this study system. We also show that 1.5 fold differences can be detected between groups simulated to have differing reproductive success, and that it is possible to detect moderate heritability values for continuous traits (h(2) similar to 0.40) with more than 80% power when using 28 moderately to highly polymorphic markers.

Conclusion: The methodologies and work flow described provide a robust approach for evaluating archived samples for pedigree-based research, even where only a proportion of the total population is sampled. The results demonstrate the feasibility of pedigree-based studies to address challenging ecological and evolutionary questions in free-living populations, where genealogies can be traced only using molecular tools, and that significant increases in pedigree assignment power can be achieved by using higher numbers of markers.

Simple preparation of positively charged silver nanoparticles for detection of anions by surface-enhanced Raman spectroscopy

Modification of citrate and hydroxylamine reduced Ag colloids with thiocholine bromide, a thiol functionalized quaternary ammonium salt, creates particles where the zeta potential is switched from the normal values of ca. -50 mV to ca. + 50 mV. These colloids are stable but can be aggregated with metal salts in much the same way as the parent colloids. They are excellent SERS substrates for detection of anionic targets since their positive zeta potentials promote adsorption of negatively charged ions. This is important because the vast majority of published SERS studies involve cationic or neutral targets. Moreover, the fact that the modifier is a quaternary ammonium ion means that the negative surface charge is maintained even at alkaline pH. The modified colloids can be used to detect compounds which cannot be detected using conventional negatively-charged citrate or hydroxylamine reduced metal nanoparticles, for example the detection limit was 5.0 x 10(-5) M for perchlorate and

Optimal design of cold-formed steel portal frames for stressed-skin action using genetic algorithm

This paper describes a stressed-skin diaphragm approach to the optimal design of the internal frame of a cold-formed steel portal framing system, in conjunction with the effect of semi-rigid joints. Both ultimate and serviceability limit states are considered. Wind load combinations are included. The designs are optimized using a real-coded niching genetic algorithm, in which both discrete and continuous decision variables are processed. For a building with two internal frames, it is shown that the material cost of the internal frame can be reduced by as much as 53%, compared with a design that ignores stressed-skin action.

New insights into the causes of human illness due to consumption of azaspiracid contaminated shellfish

Azaspiracid (AZA) poisoning was unknown until 1995 when shellfish harvested in Ireland caused illness manifesting by vomiting and diarrhoea. Further in vivo/vitro studies showed neurotoxicity linked with AZA exposure. However, the biological target of the toxin which will help explain such potent neurological activity is still unknown. A region of Irish coastline was selected and shellfish were sampled and tested for AZA using mass spectrometry. An outbreak was identified in 2010 and samples collected before and after the contamination episode were compared for their metabolite profile using high resolution mass spectrometry. Twenty eight ions were identified at higher concentration in the contaminated samples. Stringent bioinformatic analysis revealed putative identifications for seven compounds including, glutarylcarnitine, a glutaric acid metabolite. Glutaric acid, the parent compound linked with human neurological manifestations was subjected to toxicological investigations but was found to have no specific effect on the sodium channel (as was the case with AZA). However in combination, glutaric acid (1mM) and azaspiracid (50nM) inhibited the activity of the sodium channel by over 50%. Glutaric acid was subsequently detected in all shellfish employed in the study. For the first time a viable mechanism for how AZA manifests itself as a toxin is presented.

Parents’ and young people’s involvement in designing a trial of ventilator weaning

Consulting with users is considered best practice and is highly recommended in designing new trials. As part of our feasibility work, we undertook a consultation exercise with parents, ex-patients and young people prior to designing a trial of protocol-based ventilator weaning. Our aims were to (1) ascertain views on the relevance and importance of the trial; (2) determine the important parent/patient outcome measures; and (3) ascertain views on informed consent in a cluster randomized controlled trial. We conducted audio-recorded face-to-face, telephone and focus group interviews with parents and young people. Data were content analysed to generate information to address our specific consultation objectives. The setting was the north-western region of England. A total of 16 participants were interviewed: 2 parents of paediatric intensive care unit (PICU) survivors; 1 PICU survivor; and 13 young people from the former Medicines for Children Research Network. The trial objectives were deemed important and relevant, and participants considered the most important outcome measure to be the length of time on ventilation. Parents and young people did not consider written informed consent to be a necessary requirement in the context of this trial, rather awareness of unit participation in the trial was important with the opportunity of opting out of data collection. This consultation provided useful, pragmatic insights to inform trial design. We encountered significant challenges in recruiting parents and young people for this consultation exercise, and novel recruitment methods need to be considered for future work in this field. Patient and public involvement is essential to ensure that future trials answer parent-relevant questions and have meaningful outcome measures, as well as involving parents and young people in the general development of health care services.

Optimal design of long-span steel portal frames using fabricated beams

This paper considers the optimal design of fabricated steel beams for long-span portal frames. The design optimisation takes into account ultimate as well as serviceability limit states, adopting deflection limits recommended by the Steel Construction Institute (SCI). Results for three benchmark frames demonstrate the efficiency of the optimisation methodology. A genetic algorithm (GA) was used to optimise the dimensions of the plates used for the columns, rafters and haunches. Discrete decision variables were adopted for the thickness of the steel plates and continuous variables for the breadth and depth of the plates. Strategies were developed to enhance the performance of the GA including solution space reduction and a hybrid initial population half of which is derived using Latin hypercube sampling. The results show that the proposed GA-based optimisation model generates optimal and near-optimal solutions consistently. A parametric study is then conducted on frames of different spans. A significant variation in weight between fabricated and conventional hot-rolled steel portal frames is shown; for a 50 m span frame, a 14–19% saving in weight was achieved. Furthermore, since Universal Beam sections in the UK come from a discrete section library, the results could also provide overall dimensions of other beams that could be more efficient for portal frames. Eurocode 3 was used for illustrative purposes; any alternative code of practice may be used.

An efficient genetic algorithm for the design optimization of cold-formed steel portal frame buildings

The design optimization of a cold-formed steel portal frame building is considered in this paper. The proposed genetic algorithm (GA) optimizer considers both topology (i.e., frame spacing and pitch) and cross-sectional sizes of the main structural members as the decision variables. Previous GAs in the literature were characterized by poor convergence, including slow progress, that usually results in excessive computation times and/or frequent failure to achieve an optimal or near-optimal solution. This is the main issue addressed in this paper. In an effort to improve the performance of the conventional GA, a niching strategy is presented that is shown to be an effective means of enhancing the dissimilarity of the solutions in each generation of the GA. Thus, population diversity is maintained and premature convergence is reduced significantly. Through benchmark examples, it is shown that the efficient GA proposed generates optimal solutions more consistently. A parametric study was carried out, and the results included. They show significant variation in the optimal topology in terms of pitch and frame spacing for a range of typical column heights. They also show that the optimized design achieved large savings based on the cost of the main structural elements; the inclusion of knee braces at the eaves yield further savings in cost, that are significant.

Advanced design optimization of cold-formed steel portal frame buildings

The design optimization of cold-formed steel portal frame buildings is considered in this paper. The objective function is based on the cost of the members for the main frame and secondary members (i.e., purlins, girts, and cladding for walls and roofs) per unit area on the plan of the building. A real-coded niching genetic algorithm is used to minimize the cost of the frame and secondary members that are designed on the basis of ultimate limit state. It iis shown that the proposed algorithm shows effective and robust capacity in generating the optimal solution, owing to the population's diversity being maintained by applying the niching method. In the optimal design, the cost of purlins and side rails are shown to account for 25% of the total cost; the main frame members account for 27% of the total cost, claddings for the walls and roofs accounted for 27% of the total cost.