Relaxation and Metastability in the RandomWalkSAT search procedure

An analysis of the average properties of a local search resolution procedure for the satisfaction of random Boolean constraints is presented. Depending on the ratio alpha of constraints per variable, resolution takes a time T_res growing linearly (T_res \sim tau(alpha) N, alpha < alpha_d) or exponentially (T_res \sim exp(N zeta(alpha)), alpha > alpha_d) with the size N of the instance. The relaxation time tau(alpha) in the linear phase is calculated through a systematic expansion scheme based on a quantum formulation of the evolution operator. For alpha > alpha_d, the system is trapped in some metastable state, and resolution occurs from escape from this state through crossing of a large barrier. An annealed calculation of the height zeta(alpha) of this barrier is proposed. The polynomial/exponentiel cross-over alpha_d is not related to the onset of clustering among solutions.Comment: 23 pages, 11 figures. A mistake in sec. IV.B has been correcte

Developing Community Nursing Practice: Promoting Case Management and Skill Enhancement to Support Shifting the Balance of Care

Five inter-related projects were commissioned by NHS Highland to further knowledge and understanding of key issues that can be used to inform particular aspects of care delivery that supports the community nurse review. The five projects reflect some of the core elements that have been identified to maximise nurses’ contributions in community settings (Scottish Executive 2006a). The projects were designed to provide qualitative evidence of the views of community nurses regarding case management and to support the delivery of skills in community nursing practice. Additionally community nurses identified the knowledge and skills required to develop practice tools that would support areas of generalist and specialist practice, specifically around child welfare and long term conditions (heart care). The five projects were: i. Literature review on case management models in Community Nursing. ii. Action research project to support implementation of Case Management Models in community nursing. iii. Literature review on practitioners with special interest. iv. Research to inform development of practitioner tools for child protection and long term conditions (heart care). v. Research to explore skills transition to support Shifting the Balance of Care. This project focused on 3 key initiatives that are influencing community nursing and it was apparent that they all shared common goals and challenges of implementation. For this reason, it was clear that any development in service provision would impact on, and articulate with, other health, social and profession based changes and could not be implemented in isolation from other related developments that underpin shifting the balance of care. Nurses in the studies articulated insightful challenges for shifting the balance of care, and related role developments, but these were, in the majority, followed by offering practical solutions

Measurement of CP observables in B± → D(⁎)K± and B± → D(⁎)π± decays

Measurements of CP observables in B ± →D (⁎) K ± and B ± →D (⁎) π ± decays are presented, where D (⁎) indicates a neutral D or D ⁎ meson that is an admixture of D (⁎)0 and D¯ (⁎)0 states. Decays of the D ⁎ meson to the Dπ 0 and Dγ final states are partially reconstructed without inclusion of the neutral pion or photon, resulting in distinctive shapes in the B candidate invariant mass distribution. Decays of the D meson are fully reconstructed in the K ± π ∓ , K + K − and π + π − final states. The analysis uses a sample of charged B mesons produced in pp collisions collected by the LHCb experiment, corresponding to an integrated luminosity of 2.0, 1.0 and 2.0 fb −1 taken at centre-of-mass energies of s=7, 8 and 13 TeV, respectively. The study of B ± →D ⁎ K ± and B ± →D ⁎ π ± decays using a partial reconstruction method is the first of its kind, while the measurement of B ± →DK ± and B ± →Dπ ± decays is an update of previous LHCb measurements. The B ± →DK ± results are the most precise to date

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

Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

Background Individuals with rare kidney diseases account for 5–10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. Methods People aged 0–96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan–Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window). Findings Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9–16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32–0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. Interpretation Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3–5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. Funding RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity

Search for CPCP violation in the phase space of D0→π+π−π+π−D^0\rightarrow\pi^+\pi^-\pi^+\pi^- decays

A search for time-integrated $CP$ violation in the Cabibbo-suppressed decay \mbox{D^0\rightarrow\pi^+\pi^-\pi^+\pi^-} is performed using an unbinned, model-independent technique known as the energy test. This is the first application of the energy test in four-body decays. The search is performed for $P$-even $CP$ asymmetries and, for the first time, is extended to probe the $P$-odd case. Using proton-proton collision data corresponding to an integrated luminosity of 3.0 fb$^{-1}$ collected by the LHCb detector at centre-of-mass energies of $\sqrt{s}=$7 TeV and 8 TeV, the world's best sensitivity to $CP$ violation in this decay is obtained. The data are found to be consistent with the hypothesis of $CP$ symmetry with a $p$-value of $(4.6\pm0.5)\%$ in the $P$-even case, and marginally consistent with a $p$-value of $(0.6\pm0.2)\%$ in the $P$-odd case, corresponding to a significance for $CP$ non-conservation of 2.7 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-044.htm

Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury

A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury

Measurement of CPCP asymmetries in D±→η′π±D^{\pm}\rightarrow \eta^{\prime} \pi^{\pm} and Ds±→η′π±D_s^{\pm}\rightarrow \eta^{\prime} \pi^{\pm} decays

See paper for full list of authors - All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-041.html - Submitted to Phys. Lett. BInternational audienceA search for CP violation in D±→η′π± and D±s→η′π± decays is performed using proton-proton collision data, corresponding to an integrated luminosity of 3 fb−1, recorded by the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. The measured CP-violating charge asymmetries are ACP(D±→η′π±)=(−0.61±0.72±0.55±0.12)% and ACP(D±s→η′π±)=(−0.82±0.36±0.24±0.27)%, where the first uncertainties are statistical, the second systematic, and the third are the uncertainties on the ACP(D±→K0Sπ±) and ACP(D±s→ϕπ±) measurements used for calibration. The results represent the most precise measurements of these asymmetries to date

Observation of ηc(2S)→ppˉ\eta_{c}(2S) \to p \bar p and search for X(3872)→ppˉX(3872) \to p \bar p decays

The first observation of the decay $\eta_{c}(2S) \to p \bar p$ is reported using proton-proton collision data corresponding to an integrated luminosity of $3.0\rm \, fb^{-1}$ recorded by the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. The $\eta_{c}(2S)$ resonance is produced in the decay $B^{+} \to [c\bar c] K^{+}$. The product of branching fractions normalised to that for the $J/\psi$ intermediate state, ${\cal R}_{\eta_{c}(2S)}$, is measured to be \begin{align*} {\cal R}_{\eta_{c}(2S)}\equiv\frac{{\mathcal B}(B^{+} \to \eta_{c}(2S) K^{+}) \times {\mathcal B}(\eta_{c}(2S) \to p \bar p)}{{\mathcal B}(B^{+} \to J/\psi K^{+}) \times {\mathcal B}(J/\psi\to p \bar p)} =~& (1.58 \pm 0.33 \pm 0.09)\times 10^{-2}, \end{align*} where the first uncertainty is statistical and the second systematic. No signals for the decays $B^{+} \to X(3872) (\to p \bar p) K^{+}$ and $B^{+} \to \psi(3770) (\to p \bar p) K^{+}$ are seen, and the 95\% confidence level upper limits on their relative branching ratios are % found to be ${\cal R}_{X(3872)}<0.25\times10^{-2}$ and ${\cal R}_{\psi(3770))}<0.10$. In addition, the mass differences between the $\eta_{c}(1S)$ and the $J/\psi$ states, between the $\eta_{c}(2S)$ and the $\psi(2S)$ states, and the natural width of the $\eta_{c}(1S)$ are measured as \begin{align*} M_{J/\psi} - M_{\eta_{c}(1S)} =~& 110.2 \pm 0.5 \pm 0.9 \rm \, MeV, M_{\psi(2S)} -M_{\eta_{c}(2S)} =~ & 52.5 \pm 1.7 \pm 0.6 \rm \, MeV, \Gamma_{\eta_{c}(1S)} =~& 34.0 \pm 1.9 \pm 1.3 \rm \, MeV. \end{align*}Comment: 16 pages, 2 figures All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-016.htm

Measurement of B0B^0, Bs0B^0_s, B+B^+ and Λb0\Lambda^0_b production asymmetries in 7 and 8 TeV proton-proton collisions

See paper for full list of authors - All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-062.html - Submitted to Phys. Lett. B.International audienceThe B0, B0s, B+ and Λ0b hadron production asymmetries are measured using a data sample corresponding to an integrated luminosity of 3.0 fb−1, collected by the LHCb experiment in proton-proton collisions at centre-of-mass energies of 7 and 8 TeV. The measurements are performed as a function of transverse momentum and rapidity of the b hadrons within the LHCb detector acceptance. The overall production asymmetries, integrated over transverse momentum and rapidity, are also determined