Effect of rib cage deformity in primary thoracic idiopathic scoliosis on pulmonary function, airway morphology and lung volumes

Although scoliosis is defined as a Cobb angle of 10° or more as measured in the coronal plane, the combined three-dimensional distortions to both the spine and rib cage in scoliosis are best conceptualised as a thoracic deformity. There is much interest in the relationship between scoliosis and pulmonary function due to the increased morbidity of respiratory failure and mortality of those with untreated progressive scoliosis. Establishing the mechanisms of pulmonary function impairment in scoliosis is important in identifying patients with compromised lung function or those who will benefit from surgical intervention. In this work, the relationship between thoracic deformity in patients with right-sided, Lenke type 1 or 2, adolescent idiopathic scoliosis (AIS) and pulmonary function impairment is investigated. From radiographic and computer tomographic imaging, measurements of the thoracic deformity were found to be superior predictors of pulmonary function in AIS than conventional Cobb angles. A statistical shape model was constructed from biplanar radiographs to identify modes of variation in the thoracic configuration. Thoracic features such as the extent of the rib hump, narrowed convex hemithoracic width and spinal intrusion were found to be factors contributing to lung function impairment. Morphological analysis of the tracheobronchial tree demonstrated the presence of right-sided airway narrowing. In particular, patients with hypokyphosis demonstrated significant narrowing of the bronchus intermedius and its bifurcation as a result of extrinsic compression by the vertebral column. Right-sided airway obstruction was found to correspond to the presence of atelectasis and air-trapping in the right middle and lower lobe. Post-operative analysis demonstrated that restoration of natural kyphosis in patients with hypokyphosis and scoliosis resulted in improved lung function post-operatively. Although reduction in lung function in patients with scoliosis is multifactorial, variance in the sagittal thoracic profile plays a more important role in impairing lung function than is generally appreciated

GRO J1744-28, search for the counterpart: infrared photometry and spectroscopy

Using VLT/ISAAC, we detected 2 candidate counterparts to the bursting pulsar GRO J1744-28, one bright and one faint, within the X-ray error circles of XMM-Newton and Chandra. In determining the spectral types of the counterparts we applied 3 different extinction corrections; one for an all-sky value, one for a Galactic Bulge value and one for a local value. We find the local value, with an extinction law of alpha = 3.23 +- 0.01 is the only correction that results in colours and magnitudes for both bright and faint counterparts consistent with a small range of spectral types, and for the bright counterpart, consistent with the spectroscopic identification. Photometry of the faint candidate indicates it is a K7/M0 V star at a distance of 3.75 +- 1 kpc. This star would require a very low inclination angle (i < 9deg) to satisfy the mass function constraints; however it cannot be excluded as the counterpart without follow-up spectroscopy to detect emission signatures of accretion. Photometry and spectroscopy of the bright candidate indicate it is most likely a G/K III star. The spectrum does not show Br-gamma emission, a known indicator of accretion. The bright star's magnitudes are in agreement with the constraints placed on a probable counterpart by the calculations of Rappaport & Joss (1997) for an evolved star that has had its envelope stripped. The mass function indicates the counterpart should have M < 0.3 Msol for an inclination of i >= 15deg; a stripped giant, or a main sequence M3+ V star are consistent with this mass-function constraint. In both cases mass-transfer, if present, will be by wind-accretion as the counterpart will not fill its Roche lobe given the observed orbital period. The derived magnetic field of 2.4 x 10^{11} G will inhibit accretion by the propeller effect, hence its quiescent state.Comment: 12 pages, 6 figures, 4 table, MNRAS accepted Changes to the content and an increased analysis of the Galactic centre extinctio

Algebraic K-theory over the infinite dihedral group: an algebraic approach

We prove that the Waldhausen nilpotent class group of an injective index 2 amalgamated free product is isomorphic to the Farrell-Bass nilpotent class group of a twisted polynomial extension. As an application, we show that the Farrell-Jones Conjecture in algebraic K-theory can be sharpened from the family of virtually cyclic subgroups to the family of finite-by-cyclic subgroups

The biomechanics of amnion rupture: an X-ray diffraction study

Pre-term birth is the leading cause of perinatal and neonatal mortality, 40% of which are attributed to the pre-term premature rupture of amnion. Rupture of amnion is thought to be associated with a corresponding decrease in the extracellular collagen content and/or increase in collagenase activity. However, there is very little information concerning the detailed organisation of fibrillar collagen in amnion and how this might influence rupture. Here we identify a loss of lattice like arrangement in collagen organisation from areas near to the rupture site, and present a 9% increase in fibril spacing and a 50% decrease in fibrillar organisation using quantitative measurements gained by transmission electron microscopy and the novel application of synchrotron X-ray diffraction. These data provide an accurate insight into the biomechanical process of amnion rupture and highlight X-ray diffraction as a new and powerful tool in our understanding of this process

Distinct ecological fitness factors coordinated by a conserved Escherichia coli regulator during systemic bloodstream infection

The ability of bacterial pathogens to adapt to host niches is driven by the carriage and regulation of genes that benefit pathogenic lifestyles. Genes that encode virulence or fitness-enhancing factors must be regulated in response to changing host environments to allow rapid response to challenges presented by the host. Furthermore, this process can be controlled by preexisting transcription factors (TFs) that acquire new roles in tailoring regulatory networks, specifically in pathogens. However, the mechanisms underlying this process are poorly understood. The highly conserved Escherichia coli TF YhaJ exhibits distinct genome-binding dynamics and transcriptome control in pathotypes that occupy different host niches, such as uropathogenic E. coli (UPEC). Here, we report that this important regulator is required for UPEC systemic survival during murine bloodstream infection (BSI). This advantage is gained through the coordinated regulation of a small regulon comprised of both virulence and metabolic genes. YhaJ coordinates activation of both Type 1 and F1C fimbriae, as well as biosynthesis of the amino acid tryptophan, by both direct and indirect mechanisms. Deletion of yhaJ or the individual genes under its control leads to attenuated survival during BSI. Furthermore, all three systems are up-regulated in response to signals derived from serum or systemic host tissue, but not urine, suggesting a niche-specific regulatory trigger that enhances UPEC fitness via pleiotropic mechanisms. Collectively, our results identify YhaJ as a pathotype-specific regulatory aide, enhancing the expression of key genes that are collectively required for UPEC bloodstream pathogenesis

Patient emergency health-care use before hospital admission for COVID-19 and long-term outcomes in Scotland: a national cohort study

BackgroundIt is unclear what effect the pattern of health-care use before admission to hospital with COVID-19 (index admission) has on the long-term outcomes for patients. We sought to describe mortality and emergency readmission to hospital after discharge following the index admission (index discharge), and to assess associations between these outcomes and patterns of health-care use before such admissions.MethodsWe did a national, retrospective, complete cohort study by extracting data from several national databases and linking the databases for all adult patients admitted to hospital in Scotland with COVID-19. We used latent class trajectory modelling to identify distinct clusters of patients on the basis of their emergency admissions to hospital in the 2 years before the index admission. The primary outcomes were mortality and emergency readmission up to 1 year after index admission. We used multivariable regression models to explore associations between these outcomes and patient demographics, vaccination status, level of care received in hospital, and previous emergency hospital use.FindingsBetween March 1, 2020, and Oct 25, 2021, 33 580 patients were admitted to hospital with COVID-19 in Scotland. Overall, the Kaplan-Meier estimate of mortality within 1 year of index admission was 29·6% (95% CI 29·1-30·2). The cumulative incidence of emergency hospital readmission within 30 days of index discharge was 14·4% (95% CI 14·0-14·8), with the number increasing to 35·6% (34·9-36·3) patients at 1 year. Among the 33 580 patients, we identified four distinct patterns of previous emergency hospital use: no admissions (n=18 772 [55·9%]); minimal admissions (n=12 057 [35·9%]); recently high admissions (n=1931 [5·8%]), and persistently high admissions (n=820 [2·4%]). Patients with recently or persistently high admissions were older, more multimorbid, and more likely to have hospital-acquired COVID-19 than patients with no or minimal admissions. People in the minimal, recently high, and persistently high admissions groups had an increased risk of mortality and hospital readmission compared with those in the no admissions group. Compared with the no admissions group, mortality was highest in the recently high admissions group (post-hospital mortality HR 2·70 [95% CI 2·35-2·81]; pInterpretationLong-term mortality and readmission rates for patients hospitalised with COVID-19 were high; within 1 year, one in three patients had died and a third had been readmitted as an emergency. Patterns of hospital use before index admission were strongly predictive of mortality and readmission risk, independent of age, pre-existing comorbidities, and COVID-19 vaccination status. This increasingly precise identification of individuals at high risk of poor outcomes from COVID-19 will enable targeted support.FundingChief Scientist Office Scotland, UK National Institute for Health Research, and UK Research and Innovation

Shock-absorbing flooring for fall-related injury prevention in older adults and staff in hospitals and care homes: the SAFEST systematic review.

BACKGROUND: Injurious falls in hospitals and care homes are a life-limiting and costly international issue. Shock-absorbing flooring may offer part of the solution; however, evidence is required to inform decision-making. OBJECTIVES: The objectives were to assess the clinical effectiveness and cost-effectiveness of shock-absorbing flooring for fall-related injury prevention among older adults in care settings. REVIEW METHODS: A systematic review was conducted of experimental, observational, qualitative and economic studies evaluating flooring in care settings targeting older adults and/or staff. Studies identified by a scoping review (inception to May 2016) were screened, and the search of MEDLINE, AgeLine and Scopus (to September 2019) was updated, alongside other sources. Two independent reviewers assessed risk of bias in duplicate (using Cochrane's Risk of Bias 2.0 tool, the Risk Of Bias In Non-randomized Studies - of Interventions tool, or the Joanna Briggs Institute's qualitative tool). RESULTS: Of the 22 included studies, 20 assessed the outcomes (three randomised controlled trials; and seven observational, five qualitative and five economic studies) on novel floors (n = 12), sports floors (n = 5), carpet (n = 5) and wooden subfloors (n = 1). Quantitative data related to 11,857 patient/resident falls (nine studies) and 163 staff injuries (one study). Qualitative studies included patients/residents (n = 20), visitors (n = 8) and staff (n = 119). Hospital-based randomised controlled trial data were too imprecise; however, very low-quality evidence indicated that novel/sports flooring reduced injurious falls from three per 1000 patients per day on vinyl with concrete subfloors to two per 1000 patients per day (rate ratio 0.55, 95% confidence interval 0.36 to 0.84; two studies), without increasing falls rates (two studies). One care home-based randomised controlled trial found that a novel underlay produces similar injurious falls rates (high-quality evidence) and falls rates (moderate-quality evidence) to those of a plywood underlay with vinyl overlays and concrete subfloors. Very low-quality data demonstrated that, compared with rigid floors, novel/sports flooring reduced the number of falls resulting in injury in care homes (26.4% vs. 33.0%; risk ratio 0.80, 95% confidence interval 0.70 to 0.91; three studies) and hospitals (27.1% vs. 42.4%; risk ratio 0.64, 95% confidence interval 0.44 to 0.93; two studies). Fracture and head injury outcomes were imprecise; however, hip fractures reduced from 30 per 1000 falls on concrete to 18 per 1000 falls on wooden subfloors in care homes (odds ratio 0.59, 95% confidence interval 0.45 to 0.78; one study; very low-quality evidence). Four low-quality economic studies concluded that shock-absorbing flooring reduced costs and improved outcomes (three studies), or increased costs and improved outcomes (one study). One, more robust, study estimated that shock-absorbing flooring resulted in fewer quality-adjusted life-years and lower costs, if the number of falls increased on shock-absorbing floors, but that shock-absorbing flooring would be a dominant economic strategy if the number of falls remained the same. Staff found moving wheeled equipment more difficult on shock-absorbing floors, leading to workplace adaptations. Staff injuries were observed; however, very low-quality evidence suggests that these are no less frequent on rigid floors. LIMITATIONS: Evidence favouring shock-absorbing flooring is of very low quality; thus, much uncertainty remains. CONCLUSIONS: Robust evidence is lacking in hospitals and indicates that one novel floor may not be effective in care homes. Very low-quality evidence indicates that shock-absorbing floors may be beneficial; however, wider workplace implications need to be addressed. Work is required to establish a core outcome set, and future research needs to more comprehensively deal with confounding and the paucity of hospital-based studies, and better plan for workplace adaptations in the study design. STUDY REGISTRATION: This study is registered as PROSPERO CRD42019118834. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 5. See the NIHR Journals Library website for further project information

The macroecology of infectious diseases: a new perspective on global-scale drivers of pathogen distributions and impacts

© 2016 John Wiley & Sons Ltd/CNRS. Identifying drivers of infectious disease patterns and impacts at the broadest scales of organisation is one of the most crucial challenges for modern science, yet answers to many fundamental questions remain elusive. These include what factors commonly facilitate transmission of pathogens to novel host species, what drives variation in immune investment among host species, and more generally what drives global patterns of parasite diversity and distribution? Here we consider how the perspectives and tools of macroecology, a field that investigates patterns and processes at broad spatial, temporal and taxonomic scales, are expanding scientific understanding of global infectious disease ecology. In particular, emerging approaches are providing new insights about scaling properties across all living taxa, and new strategies for mapping pathogen biodiversity and infection risk. Ultimately, macroecology is establishing a framework to more accurately predict global patterns of infectious disease distribution and emergence