Lamb Street, Coventry, West Midlands : post-excavation assessment report

Between December 2018 and March 2019, Salford Archaeology carried out an archaeological excavation on Lamb Street, within the historic core of Coventry city centre (centred on NGR SP 33270 79350). This uncovered significant remains deriving from the medieval and post-medieval periods, together with a considerable assemblage of artefacts. Some rare evidence for Roman activity in Coventry was also recovered from the excavation. Following completion of the fieldwork, an assessment was made of the project archive, with a view todefining the costs of completing an appropriate programme of post-excavation analysis and publication. This assessment examined the results of the excavationand assessed the potential for further analysis of each category of data with regard to the project’s research aims, in accordance with professional guidelines laid out by Historic England

An evaluation of strategies used by the Landscapes and Policy Hub to achieve interdisciplinary and transdisciplinary research

The report presents an evaluation of the Landscapes and Policy Hub's approach to interdisciplinary and transdisciplinary research. The hub was a national, four year, $15 million collaborative research program. The focus of the evaluation was for researchers to reflect on the effectiveness of strategies used by the hub to facilitate interdisciplinarity (where researchers from different disciplines work together to solve problems) and transdisciplinarity (where researchers from different disciplines work in partnership with research users to solve problems). The evaluation was commissioned in the final phase of the hub’s life in the interests of improving performance of future interdisciplinary and transdisciplinary research. It was based on a number of strategies that had been implemented by the hub to encourage and facilitate interdisciplinary research occurring in partnership with research users. The aim of the evaluation was to improve performance of future interdisciplinary and transdisciplinary research. Six recommendations are presented

Predictability of evolutionary trajectories in fitness landscapes

Experimental studies on enzyme evolution show that only a small fraction of all possible mutation trajectories are accessible to evolution. However, these experiments deal with individual enzymes and explore a tiny part of the fitness landscape. We report an exhaustive analysis of fitness landscapes constructed with an off-lattice model of protein folding where fitness is equated with robustness to misfolding. This model mimics the essential features of the interactions between amino acids, is consistent with the key paradigms of protein folding and reproduces the universal distribution of evolutionary rates among orthologous proteins. We introduce mean path divergence as a quantitative measure of the degree to which the starting and ending points determine the path of evolution in fitness landscapes. Global measures of landscape roughness are good predictors of path divergence in all studied landscapes: the mean path divergence is greater in smooth landscapes than in rough ones. The model-derived and experimental landscapes are significantly smoother than random landscapes and resemble additive landscapes perturbed with moderate amounts of noise; thus, these landscapes are substantially robust to mutation. The model landscapes show a deficit of suboptimal peaks even compared with noisy additive landscapes with similar overall roughness. We suggest that smoothness and the substantial deficit of peaks in the fitness landscapes of protein evolution are fundamental consequences of the physics of protein folding.Comment: 14 pages, 7 figure

Assessment of the consistency and robustness of results from a multicenter trial of remission maintenance therapy for acute myeloid leukemia

<p>Abstract</p> <p>Background</p> <p>Data from a randomized multinational phase 3 trial of 320 adults with acute myeloid leukemia (AML) demonstrated that maintenance therapy with 3-week cycles of histamine dihydrochloride plus low-dose interleukin-2 (HDC/IL-2) for up to 18 months significantly improved leukemia-free survival (LFS) but lacked power to detect an overall survival (OS) difference.</p> <p>Purpose</p> <p>To assess the consistency of treatment benefit across patient subsets and the robustness of data with respect to trial centers and endpoints.</p> <p>Methods</p> <p>Forest plots were constructed with hazard ratios (HRs) of HDC/IL-2 treatment effects versus no treatment (control) for prospectively defined patient subsets. Inconsistency coefficients (I²) and interaction tests (X²) were used to detect any differences in benefit among subsets. Robustness of results to the elimination of individual study centers was performed using "leave-one-center-out" analyses. Associations between treatment effects on the endpoints were evaluated using weighted linear regression between HRs for LFS and OS estimated within countries.</p> <p>Results</p> <p>The benefit of HDC/IL-2 over controls was statistically consistent across all subsets defined by baseline prognostic variables. I²and <it>P</it>-values of X²ranged from 0.00 to 0.51 and 0.14 to 0.91, respectively. Treatment effects were statistically significant in 14 of 28 subsets analyzed. The "leave-one-center-out" analysis confirmed that no single center dominated (<it>P</it>-values ranged from 0.004 to 0.020 [mean 0.009]). The HRs representing the HDC/IL-2 effects on LFS and OS were strongly correlated at the country level (R²= 0.84).</p> <p>Limitations</p> <p>Small sample sizes in some of the subsets analyzed.</p> <p>Conclusions</p> <p>These analyses confirm the consistency and robustness of the HDC/IL-2 effect as compared with no treatment. LFS may be an acceptable surrogate for OS in future AML trials. Analyses of consistency and robustness may aid interpretation of data from multicenter trials, especially in populations with rare diseases, when the size of randomized clinical trials is limited.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00003991">NCT00003991</a></p

Experiences of training and implementation of integrated management of childhood illness (IMCI) in South Africa: a qualitative evaluation of the IMCI case management training course

<p>Abstract</p> <p>Background</p> <p>Integrated Management of Childhood Illness (IMCI) is a strategy to reduce mortality and morbidity in children under-5 years by improving management of common illnesses at primary level. IMCI has been shown to improve health worker performance, but constraints have been identified in achieving sufficient coverage to improve child survival, and implementation remains sub-optimal. At the core of the IMCI strategy is a clinical guideline whereby health workers use a series of algorithms to assess and manage a sick child, and give counselling to carers. IMCI is taught using a structured 11-day training course that combines classroom work with clinical practise; a variety of training techniques are used, supported by comprehensive training materials and detailed instructions for facilitators.</p> <p>Methods</p> <p>We conducted focus group discussions with IMCI trained health workers to explore their experiences of the methodology and content of the IMCI training course, whether they thought they gained the skills required for implementation, and their experiences of follow-up visits.</p> <p>Results</p> <p>Health workers found the training interesting, informative and empowering, and there was consensus that it improved their skills in managing sick children. They appreciated the variety of learning methods employed, and felt that repetition was important to reinforce knowledge and skills. Facilitators were rated highly for their knowledge and commitment, as well as their ability to identify problems and help participants as required. However, health workers felt strongly that the training time was too short to acquire skills in all areas of IMCI. Their increased confidence in managing sick children was identified by health workers as an enabling factor for IMCI implementation in the workplace, but additional time required for IMCI consultations was expressed as a major barrier. Although follow-up visits were described as very helpful, these were often delayed and there was no ongoing clinical supervision.</p> <p>Conclusion</p> <p>The IMCI training course was reported to be an effective method of acquiring skills, but more time is required, either during the course, or with follow-up, to improve IMCI implementation. Innovative solutions may be required to ensure that adequate skills are acquired and maintained.</p

Sperm competition-induced plasticity in the speed of spermatogenesis

Background: Sperm competition between rival ejaculates over the fertilization of ova typically selects for the production of large numbers of sperm. An obvious way to increase sperm production is to increase testis size, and most empirical work has focussed on this parameter. Adaptive plasticity in sperm production rate could also arise due to variation in the speed with which each spermatozoon is produced, but whether animals can respond to relevant environmental conditions by modulating the kinetics of spermatogenesis in this way has not been experimentally investigated. Results: Here we demonstrate that the simultaneously hermaphroditic flatworm Macrostomum lignano exhibits substantial plasticity in the speed of spermatogenesis, depending on the social context: worms raised under higher levels of sperm competition produce sperm faster. Conclusions: Our findings overturn the prevailing view that the speed of spermatogenesis is a static property of a genotype, and demonstrate the profound impact that social environmental conditions can exert upon a key developmental process. We thus identify, to our knowledge, a novel mechanism through which sperm production rate is maximised under sperm competition

Logopenic and nonfluent variants of primary progressive aphasia are differentiated by acoustic measures of speech production

Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r2 = 0.47) with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word repetition task may be sufficient for detecting most cases of apraxia of speech and distinguishing between nfvPPA and lvPPA

Applying the Risk of Bias Tool in a Systematic Review of Combination Long-Acting Beta-Agonists and Inhaled Corticosteroids for Persistent Asthma

Background: The Risk of Bias (RoB) tool is used to assess internal validity of randomized controlled trials (RCTs). Our objectives were to: 1) evaluate inter-rater agreement of the RoB tool; 2) determine the time to access supplemental study information; 3) compare the RoB tool with the Jadad scale and Schulz allocation concealment (AC); and 4) examine the relationship between RoB and effect estimates. Methods: We conducted a systematic review of long-acting beta agonists (LABA) combined with inhaled corticosteroids (ICS) for adults with persistent asthma. Two reviewers independently assessed 107 trials using RoB, Jadad, and AC. One reviewer searched for study protocols. We assessed inter-rater agreement using weighted Kappa (k) and the correlation between tools using Kendall’s Tau (t). Mean differences in effect sizes for RCTs with different RoB were calculated using inverse variance method and random effects model. Results: Trials had good Jadad scores (median 4, IQR 3-4); however, 85 % had unclear AC and 87 % high RoB. The factor that most influenced RoB was the potential inappropriate influence of study sponsors (95 % industry funded). Agreement on RoB domains was fair (k = 0.40) to almost perfect (k = 0.86), and moderate for overall RoB (k = 0.41). Median time to complete RoB assessments was 21 minutes (IQR 14-27) and 12 minutes (IQR 9-16) to search for protocols. Protocols were identified for 5/42 studies (12%); in 3 cases the assessment of selective outcome reporting changed. There was low correlation between overall RoB vs. Jadad (t =0.04