Discrete fragmentation systems in weighted ℓ1 spaces

We investigate an infinite, linear system of ordinary differential equations that models the evolution of fragmenting clusters. We assume that each cluster is composed of identical units (monomers) and we allow mass to be lost, gained or conserved during each fragmentation event. By formulating the initial-value problem for the system as an abstract Cauchy problem (ACP), posed in an appropriate weighted ℓ1 space, and then applying perturbation results from the theory of operator semigroups, we prove the existence and uniqueness of physically relevant, classical solutions for a wide class of initial cluster distributions. Additionally, we establish that it is always possible to identify a weighted ℓ1 space on which the fragmentation semigroup is analytic, which immediately implies that the corresponding ACP is well-posed for any initial distribution belonging to this particular space. We also investigate the asymptotic behaviour of solutions, and show that, under appropriate restrictions on the fragmentation coefficients, solutions display the expected long-term behaviour of converging to a purely monomeric steady state. Moreover, when the fragmentation semigroup is analytic, solutions are shown to decay to this steady state at an explicitly defined exponential rate

Effectiveness and cost-effectiveness of basic versus biofeedback-mediated intensive pelvic floor muscle training for female stress or mixed urinary incontinence: protocol for the OPAL randomised trial

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordIntroduction Accidental urine leakage is a distressing problem that affects around one in three women. The main types of urinary incontinence (UI) are stress, urgency and mixed, with stress being most common. Current UK guidelines recommend that women with UI are offered at least 3 months of pelvic floor muscle training (PFMT). There is evidence that PFMT is effective in treating UI, however it is not clear how intensively women have to exercise to give the maximum sustained improvement in symptoms, and how we enable women to achieve this. Biofeedback is an adjunct to PFMT that may help women exercise more intensively for longer, and thus may improve continence outcomes when compared with PFMT alone. A Cochrane review was inconclusive about the benefit of biofeedback, indicating the need for further evidence. Methods and analysis This multicentre randomised controlled trial will compare the effectiveness and cost-effectiveness of PFMT versus biofeedback-mediated PFMT for women with stress UI or mixed UI. The primary outcome is UI severity at 24 months after randomisation. The primary economic outcome measure is incremental cost per quality-adjusted life-year at 24 months. Six hundred women from UK community, outpatient and primary care settings will be randomised and followed up via questionnaires, diaries and pelvic floor assessment. All participants are offered six PFMT appointments over 16 weeks. The use of clinic and home biofeedback is added to PFMT for participants in the biofeedback group. Group allocation could not be masked from participants and healthcare staff. An intention-to-treat analysis of the primary outcome will estimate the mean difference between the trial groups at 24 months using a general linear mixed model adjusting for minimisation covariates and other important prognostic covariates, including the baseline score. Ethics and dissemination Approval granted by the West of Scotland Research Ethics Committee 4 (16/LO/0990). Written informed consent will be obtained from participants by the local research team. Serious adverse events will be reported to the data monitoring and ethics committee, the ethics committee and trial centres as required. A Standard Protocol Items: Recommendations for Interventional Trials checklist and figure are available for this protocol. The results will be published in international journals and included in the relevant Cochrane review. Trial registration number ISRCTN57746448; Pre-results.National Institute for Health Research (NIHR

'The bike breaks down. What are they going to do?' Actor-networks and the Bicycles for Development movement

This manuscript reports on an empirical study of ‘Bicycles for Development’ (BFD) – a nascent movement whereby used bicycles are collected (often in the global North) and distributed in development contexts (often in the global South) with the aim of achieving a range of positive social outcomes (e.g., access to education). Drawing from interviews (n=32) with participants from 19 BFD organizations, and informed by Actor-Network Theory (ANT), the analysis presented herein specifically highlights three key factors that facilitate and/or hinder BFD work: 1) government regulations that potentially stem or ease the flow of bicycles into development contexts; 2) the bicycle’s material constitution, and specifically its sturdiness (or lack thereof); and 3) environmental conditions that impact how bicycles are made, distributed, and used. A key theme that cuts across these findings is the potential for non-humans to cause ‘frictions’ that potentially disrupt, divert, but also help in realizing the programs of action of BFD organizations. We consider the relevance of these findings for both the BFD movement in particular and the wider Sport for Development and Peace (SDP) movement in general. Based on study findings, we argue for ANT as a useful framework for achieving a widened analytical focus and thus for delivering more robust accounts of development contexts under study

Hα star formation main sequence in cluster and field galaxies at z ∼ 1.6

We calculate Hα-based star formation rates and determine the star formation rate–stellar mass relation for members of three Spitzer Adaptation of the Red-Sequence Cluster Survey (SpARCS) clusters at z ∼ 1.6 and serendipitously identified field galaxies at similar redshifts to the clusters. We find similar star formation rates in cluster and field galaxies throughout our range of stellar masses. The results are comparable to those seen in other clusters at similar redshifts, and consistent with our previous photometric evidence for little quenching activity in clusters. One possible explanation for our results is that galaxies in our z ∼ 1.6 clusters have been accreted too recently to show signs of environmental quenching. It is also possible that the clusters are not yet dynamically mature enough to produce important environmental quenching effects shown to be important at low redshift, such as ram-pressure stripping or harassment

Tonsillectomy compared with conservative management in patients over 16 years with recurrent sore throat:the NATTINA RCT and economic evaluation

BACKGROUND: The place of tonsillectomy in the management of sore throat in adults remains uncertain.OBJECTIVES: To establish the clinical effectiveness and cost-effectiveness of tonsillectomy, compared with conservative management, for tonsillitis in adults, and to evaluate the impact of alternative sore throat patient pathways.DESIGN: This was a multicentre, randomised controlled trial comparing tonsillectomy with conservative management. The trial included a qualitative process evaluation and an economic evaluation.SETTING: The study took place at 27 NHS secondary care hospitals in Great Britain.PARTICIPANTS: A total of 453 eligible participants with recurrent sore throats were recruited to the main trial.INTERVENTIONS: Patients were randomised on a 1 : 1 basis between tonsil dissection and conservative management (i.e. deferred surgery) using a variable block-stratified design, stratified by (1) centre and (2) severity.MAIN OUTCOME MEASURES: The primary outcome measure was the total number of sore throat days over 24 months following randomisation. The secondary outcome measures were the number of sore throat episodes and five characteristics from Sore Throat Alert Return, describing severity of the sore throat, use of medications, time away from usual activities and the Short Form questionnaire-12 items. Additional secondary outcomes were the Tonsil Outcome Inventory-14 total and subscales and Short Form questionnaire-12 items 6 monthly. Evaluation of the impact of alternative sore throat patient pathways by observation and statistical modelling of outcomes against baseline severity, as assessed by Tonsil Outcome Inventory-14 score at recruitment. The incremental cost per sore throat day avoided, the incremental cost per quality-adjusted life-year gained based on responses to the Short Form questionnaire-12 items and the incremental net benefit based on costs and responses to a contingent valuation exercise. A qualitative process evaluation examined acceptability of trial processes and ramdomised arms.RESULTS: There was a median of 27 (interquartile range 12-52) sore throats over the 24-month follow-up. A smaller number of sore throats was reported in the tonsillectomy arm [median 23 (interquartile range 11-46)] than in the conservative management arm [median 30 (interquartile range 14-65)]. On an intention-to-treat basis, there were fewer sore throats in the tonsillectomy arm (incident rate ratio 0.53, 95% confidence interval 0.43 to 0.65). Sensitivity analyses confirmed this, as did the secondary outcomes. There were 52 episodes of post-operative haemorrhage reported in 231 participants undergoing tonsillectomy (22.5%). There were 47 re-admissions following tonsillectomy (20.3%), 35 relating to haemorrhage. On average, tonsillectomy was more costly and more effective in terms of both sore throat days avoided and quality-adjusted life-years gained. Tonsillectomy had a 100% probability of being considered cost-effective if the threshold for an additional quality-adjusted life year was £20,000. Tonsillectomy had a 69% probability of having a higher net benefit than conservative management. Trial processes were deemed to be acceptable. Patients who received surgery were unanimous in reporting to be happy to have received it.LIMITATIONS: The decliners who provided data tended to have higher Tonsillectomy Outcome Inventory-14 scores than those willing to be randomised implying that patients with a higher burden of tonsillitis symptoms may have declined entry into the trial.CONCLUSIONS: The tonsillectomy arm had fewer sore throat days over 24 months than the conservative management arm, and had a high probability of being considered cost-effective over the ranges considered. Further work should focus on when tonsillectomy should be offered. National Trial of Tonsillectomy IN Adults has assessed the effectiveness of tonsillectomy when offered for the current UK threshold of disease burden. Further research is required to define the minimum disease burden at which tonsillectomy becomes clinically effective and cost-effective.TRIAL REGISTRATION: This trial is registered as ISRCTN55284102.FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/146/06) and is published in full in Health Technology Assessment; Vol. 27, No. 31. See the NIHR Funding and Awards website for further award information. </p

DNMT3B PWWP mutations cause hypermethylation of heterochromatin

The correct establishment of DNA methylation patterns is vital for mammalian development and is achieved by the de novo DNA methyltransferases DNMT3A and DNMT3B. DNMT3B localises to H3K36me3 at actively transcribing gene bodies via its PWWP domain. It also functions at heterochromatin through an unknown recruitment mechanism. Here we find that knockout of DNMT3B causes loss of methylation predominantly at H3K9me3-marked heterochromatin and that DNMT3B PWWP domain mutations or deletion result in striking increases of methylation in H3K9me3-marked heterochromatin. Removal of the N-terminal region of DNMT3B affects its ability to methylate H3K9me3-marked regions. This region of DNMT3B directly interacts with HP1 and facilitates the bridging of DNMT3B with H3K9me3-marked nucleosomes in vitro. Our results suggest that DNMT3B is recruited to H3K9me3 marked heterochromatin in a PWWP-independent mannerthat is facilitated by the protein’s N-terminal region through an interaction with a key heterochromatin protein. More generally, we suggest that DNMT3B plays a role in DNA methylation homeostasis at heterochromatin, a process which is disrupted in cancer, aging and Immunodeficiency, Centromeric Instability and Facial Anomalies (ICF) syndrome

The GOGREEN Survey: Evidence of an excess of quiescent disks in clusters at 1.0<z<1.41.0<z<1.4

We present results on the measured shapes of 832 galaxies in 11 galaxy clusters at 1.0 < z <1.4 from the GOGREEN survey. We measure the axis ratio ($q$), the ratio of the minor to the major axis, of the cluster galaxies from near-infrared Hubble Space Telescope imaging using S\'ersic profile fitting and compare them with a field sample. We find that the median $q$ of both star-forming and quiescent galaxies in clusters increases with stellar mass, similar to the field. Comparing the axis ratio distributions between clusters and the field in four mass bins, the distributions for star-forming galaxies in clusters are consistent with those in the field. Conversely, the distributions for quiescent galaxies in the two environments are distinct, most remarkably in $10.1\leq\log(M/{\rm M}_{\odot})<10.5$ where clusters show a flatter distribution, with an excess at low $q$. Modelling the distribution with oblate and triaxial components, we find that the cluster and field sample difference is consistent with an excess of flattened oblate quiescent galaxies in clusters. The oblate population contribution drops at high masses, resulting in a narrower $q$ distribution in the massive population than at lower masses. Using a simple accretion model, we show that the observed $q$ distributions and quenched fractions are consistent with a scenario where no morphological transformation occurs for the environmentally quenched population in the two intermediate mass bins. Our results suggest that environmental quenching mechanism(s) likely produce a population that has a different morphological mix than those resulting from the dominant quenching mechanism in the field.Comment: Accepted for publication in ApJ. 25 pages, 15 figure

Retrotransposons Are the Major Contributors to the Expansion of the \u3ci\u3eDrosophila ananassae\u3c/i\u3e Muller F Element

The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (∼5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (\u3e18.7 Mb) in D. ananassae. To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4-Mb region of the D. ananassae F element, and a 1.7-Mb region from the D element for comparison. We find that transposons (particularly LTR and LINE retrotransposons) are major contributors to this expansion (78.6%), while Wolbachia sequences integrated into the D. ananassae genome are minor contributors (0.02%). Both D. melanogaster and D. ananassae F-element genes exhibit distinct characteristics compared to D-element genes (e.g., larger coding spans, larger introns, more coding exons, and lower codon bias), but these differences are exaggerated in D. ananassae. Compared to D. melanogaster, the codon bias observed in D. ananassae F-element genes can primarily be attributed to mutational biases instead of selection. The 5′ ends of F-element genes in both species are enriched in dimethylation of lysine 4 on histone 3 (H3K4me2), while the coding spans are enriched in H3K9me2. Despite differences in repeat density and gene characteristics, D. ananassae F-element genes show a similar range of expression levels compared to genes in euchromatic domains. This study improves our understanding of how transposons can affect genome size and how genes can function within highly repetitive domains