Efficient chaining of seeds in ordered trees

We consider here the problem of chaining seeds in ordered trees. Seeds are mappings between two trees Q and T and a chain is a subset of non overlapping seeds that is consistent with respect to postfix order and ancestrality. This problem is a natural extension of a similar problem for sequences, and has applications in computational biology, such as mining a database of RNA secondary structures. For the chaining problem with a set of m constant size seeds, we describe an algorithm with complexity O(m2 log(m)) in time and O(m2) in space

Fixed-bearing Medial Unicompartmental Knee Arthroplasty Restores Neither the Medial Pivoting Behavior Nor the Ligament Forces of the Intact Knee in Passive Flexion

Medial unicompartmental knee arthroplasty (UKA) is an accepted treatment for isolated medial osteoarthritis. However, using an improper thickness for the tibial component may contribute to early failure of the prosthesis or disease progression in the unreplaced lateral compartment. Little is known of the effect of insert thickness on both knee kinematics and ligament forces. Therefore, a computational model of the tibiofemoral joint was used to determine how non-conforming, fixed bearing medial UKA affects tibiofemoral kinematics and tension in the medial collateral ligament (MCL) and the anterior cruciate ligament (ACL) during passive knee flexion. Fixed bearing medial UKA could not maintain the medial pivoting that occurred in the intact knee from 0° to 30° of passive flexion. Abnormal anterior-posterior (AP) translations of the femoral condyles relative to the tibia delayed coupled internal tibial rotation, which occurred in the intact knee from 0° to 30° flexion, but occurred from 30° to 90° flexion following UKA. Increasing or decreasing tibial insert thickness following medial UKA also failed to restore the medial pivoting behavior of the intact knee despite modulating MCL and ACL forces. Reduced AP constraint in non-conforming medial UKA relative to the intact knee leads to abnormal condylar translations regardless of insert thickness even with intact cruciate and collateral ligaments. This finding suggests that the conformity of the medial compartment as driven by the medial meniscus and articular morphology plays an important role in controlling AP condylar translations in the intact tibiofemoral joint during passive flexion

Quiver GIT for varieties with tilting bundles

In the setting of a variety X admitting a tilting bundle T we consider the problem of constructing X as a quiver GIT quotient of the algebra A:=EndX(T)opA:=EndX(T)op . We prove that if the tilting equivalence restricts to a bijection between the skyscraper sheaves of X and the closed points of a quiver representation moduli functor for A=EndX(T)opA=EndX(T)op then X is indeed a fine moduli space for this moduli functor, and we prove this result without any assumptions on the singularities of X. As an application we consider varieties which are projective over an affine base such that the fibres are of dimension 1, and the derived pushforward of the structure sheaf on X is the structure sheaf on the base. In this situation there is a particular tilting bundle on X constructed by Van den Bergh, and our result allows us to reconstruct X as a quiver GIT quotient for an easy to describe stability condition and dimension vector. This result applies to flips and flops in the minimal model program, and in the situation of flops shows that both a variety and its flop appear as moduli spaces for algebras produced from different tilting bundles on the variety. We also give an application to rational surface singularities, showing that their minimal resolutions can always be constructed as quiver GIT quotients for specific dimension vectors and stability conditions. This gives a construction of minimal resolutions as moduli spaces for all rational surface singularities, generalising the G-Hilbert scheme moduli space construction which exists only for quotient singularities

Rescaling the local: multi-academy trusts, private monopoly and statecraft in England

For the past six years successive UK governments in England have introduced reforms intended to usher in less aggregated, top-down, bureaucratically overloaded models of service delivery as well as secure conditions for greater school autonomy. Yet the ‘hollowing out’ of local government has not resulted in less bureaucracy on the ground or less regulation from above, nor has it diminished hierarchy as an organising principle of education governance. In some cases, monopolies and monopolistic practices dominated by powerful bureaucracies and professional groups persist, albeit realised through the involvement of new actors and organisations from business and philanthropy. In this paper I adopt a governmentality perspective to explore the political significance of large multi-academy trusts (MATs) – private sponsors contracted by central government to run publicly funded schools – to the generation of new scalar hierarchies and accountability infrastructures that assist in bringing the gaze of government to bear upon the actions of schools that are otherwise less visible under local government management. On this account, it is argued, MATs are integral to statecraft and the invention and assemblage of particular apparatuses for intervening upon specific organisations, spaces and peoples

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Masculinity—Femininity

Six areas of research in developmental and personality psychology concerning sex-typed traits, attitudes, and interests are identified as elements of a common “masculinity-femininity” paradigm needing reexamination. The masculinity-femininity paradigm is defined in relationship to Money and Ehrhardt's model for gender identity differentiation and dimorphism. The six lines of research in the masculinity-femininity paradigm are then briefly critically examined: (1) the measurability of masculinity-femininity as a trait, (2) the identification model of masculinity-femininity development, (3) the effects of father absence on boys, (4) correlates of masculinity-femininity in life adjustment, (5) cross-sex identity in males, and (6) sex role identity problems in black males. The empirical and conceptual problems in each line of research are explored, and are substantial enough to suggest the need for alternate paradigms. Two alternate models for masculinity-femininity development are briefly sketched. First, masculinity-femininity development is analogized to moral development, as a phasic process ideally leading to sex role transcendence and androgyny. Second, the acquisition of masculinity-femininity is analogized to language acquisition, as a highly symbol-dependent learning process contingent upon the interaction between an innate acquisition apparatus and a corpus of observed sex role behavior.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45567/1/11199_2004_Article_BF00288009.pd

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study

Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding UK Research and Innovation and National Institute for Health Research

Thermal modeling of zone-melting-recrystallization processing of silicon-on-insulator film structures

A numerical simulation model that considers changes in thermal and radiation properties during zone-melting-recrystallization processing of silicon-on-insulator film structures with a graphite strip heater was developed. A series of numerical experiments were conducted to investigate the conductive, convective, and radiative parameters affecting the process. The variability of the thermal conductivity of silicon as a function of temperature at the premelting stage and the variation in thermal conductivity due to the multilayer nature of the structure were found not to affect of the temperature distribution during processing. The convective heat losses induced by the inert gas in the processing chamber does not affect significantly the temperature profiles in the film structure, but can reduce the melt zone width by 10%-25%. The study of radiative effects focused on the effects of varying the width and height of the graphite strip and the distance between the graphite strip and the film structure. These parameters significantly affect the temperature distribution and the width of the melt zone. The relationships between the convection and radiation parameters and the resultant melt zone width are presented in graphical form for use in design optimization