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Universal skolem sets
No full textIt is a longstanding open problem whether there is an algorithm to decide the Skolem Problem for linear recurrence sequences, namely whether a given such sequence has a zero term. In this paper we introduce the notion of a Universal Skolem Set: an infinite subset S of the positive integers such that there is an effective procedure that inputs a linear recurrence sequence u = (u(n)) n ≥ 0 and decides whether u(n) = 0 for some n∈S. The main technical contribution of the paper is to exhibit such a set
Smoking cessation for improving mental health
No full textBackground:
There is a common perception that smoking generally helps people to manage stress, and may be a form of 'self‐medication' in people with mental health conditions. However, there are biologically plausible reasons why smoking may worsen mental health through neuroadaptations arising from chronic smoking, leading to frequent nicotine withdrawal symptoms (e.g. anxiety, depression, irritability), in which case smoking cessation may help to improve rather than worsen mental health.
Objectives:
To examine the association between tobacco smoking cessation and change in mental health.
Search Methods:
We searched the Cochrane Tobacco Addiction Group's Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO, and the trial registries clinicaltrials.gov and the International Clinical Trials Registry Platform, from 14 April 2012 to 07 January 2020. These were updated searches of a previously‐conducted non‐Cochrane review where searches were conducted from database inception to 13 April 2012.
Selection Criteria:
We included controlled before‐after studies, including randomised controlled trials (RCTs) analysed by smoking status at follow‐up, and longitudinal cohort studies. In order to be eligible for inclusion studies had to recruit adults who smoked tobacco, and assess whether they quit or continued smoking during the study. They also had to measure a mental health outcome at baseline and at least six weeks later.
Data Collection and Analysis:
We followed standard Cochrane methods for screening and data extraction. Our primary outcomes were change in depression symptoms, anxiety symptoms or mixed anxiety and depression symptoms between baseline and follow‐up. Secondary outcomes included change in symptoms of stress, psychological quality of life, positive affect, and social impact or social quality of life, as well as new incidence of depression, anxiety, or mixed anxiety and depression disorders.
We assessed the risk of bias for the primary outcomes using a modified ROBINS‐I tool. For change in mental health outcomes, we calculated the pooled standardised mean difference (SMD) and 95% confidence interval (95% CI) for the difference in change in mental health from baseline to follow‐up between those who had quit smoking and those who had continued to smoke. For the incidence of psychological disorders, we calculated odds ratios (ORs) and 95% CIs. For all meta‐analyses we used a generic inverse variance random‐effects model and quantified statistical heterogeneity using I2. We conducted subgroup analyses to investigate any differences in associations between sub‐populations, i.e. unselected people with mental illness, people with physical chronic diseases.
We assessed the certainty of evidence for our primary outcomes (depression, anxiety, and mixed depression and anxiety) and our secondary social impact outcome using the eight GRADE considerations relevant to non‐randomised studies (risk of bias, inconsistency, imprecision, indirectness, publication bias, magnitude of the effect, the influence of all plausible residual confounding, the presence of a dose‐response gradient).
Main Results:
We included 102 studies representing over 169,500 participants. Sixty‐two of these were identified in the updated search for this review and 40 were included in the original version of the review. Sixty‐three studies provided data on change in mental health, 10 were included in meta‐analyses of incidence of mental health disorders, and 31 were synthesised narratively.
For all primary outcomes, smoking cessation was associated with an improvement in mental health symptoms compared with continuing to smoke: anxiety symptoms (SMD −0.28, 95% CI −0.43 to −0.13; 15 studies, 3141 participants; I2 = 69%; low‐certainty evidence); depression symptoms: (SMD −0.30, 95% CI −0.39 to −0.21; 34 studies, 7156 participants; I2 = 69%' very low‐certainty evidence); mixed anxiety and depression symptoms (SMD −0.31, 95% CI −0.40 to −0.22; 8 studies, 2829 participants; I2 = 0%; moderate certainty evidence). These findings were robust to preplanned sensitivity analyses, and subgroup analysis generally did not produce evidence of differences in the effect size among subpopulations or based on methodological characteristics. All studies were deemed to be at serious risk of bias due to possible time‐varying confounding, and three studies measuring depression symptoms were judged to be at critical risk of bias overall. There was also some evidence of funnel plot asymmetry. For these reasons, we rated our certainty in the estimates for anxiety as low, for depression as very low, and for mixed anxiety and depression as moderate.
For the secondary outcomes, smoking cessation was associated with an improvement in symptoms of stress (SMD −0.19, 95% CI −0.34 to −0.04; 4 studies, 1792 participants; I2 = 50%), positive affect (SMD 0.22, 95% CI 0.11 to 0.33; 13 studies, 4880 participants; I2 = 75%), and psychological quality of life (SMD 0.11, 95% CI 0.06 to 0.16; 19 studies, 18,034 participants; I2 = 42%). There was also evidence that smoking cessation was not associated with a reduction in social quality of life, with the confidence interval incorporating the possibility of a small improvement (SMD 0.03, 95% CI 0.00 to 0.06; 9 studies, 14,673 participants; I2 = 0%). The incidence of new mixed anxiety and depression was lower in people who stopped smoking compared with those who continued (OR 0.76, 95% CI 0.66 to 0.86; 3 studies, 8685 participants; I2 = 57%), as was the incidence of anxiety disorder (OR 0.61, 95% CI 0.34 to 1.12; 2 studies, 2293 participants; I2 = 46%). We deemed it inappropriate to present a pooled estimate for the incidence of new cases of clinical depression, as there was high statistical heterogeneity (I2 = 87%).
Authors' Conclusions:
Taken together, these data provide evidence that mental health does not worsen as a result of quitting smoking, and very low‐ to moderate‐certainty evidence that smoking cessation is associated with small to moderate improvements in mental health. These improvements are seen in both unselected samples and in subpopulations, including people diagnosed with mental health conditions. Additional studies that use more advanced methods to overcome time‐varying confounding would strengthen the evidence in this area
The relation between parietal GABA concentration and numerical skills
No full textSeveral scientific, engineering, and medical advancements are based on breakthroughs made by people who excel in mathematics. Our current understanding of the underlying brain networks stems primarily from anatomical and functional investigations, but our knowledge of how neurotransmitters subserve numerical skills, the building block of mathematics, is scarce. Using 1H magnetic resonance spectroscopy (N = 54, 3T, semi-LASER sequence, TE = 32 ms, TR = 3.5 s), the study examined the relation between numerical skills and the brain’s major inhibitory (GABA) and excitatory (glutamate) neurotransmitters. A negative association was found between the performance in a number sequences task and the resting concentration of GABA within the left intraparietal sulcus (IPS), a key region supporting numeracy. The relation between GABA in the IPS and number sequences was specific to (1) parietal but not frontal regions and to (2) GABA but not glutamate. It was additionally found that the resting functional connectivity of the left IPS and the left superior frontal gyrus was positively associated with number sequences performance. However, resting GABA concentration within the IPS explained number sequences performance above and beyond the resting frontoparietal connectivity measure. Our findings further motivate the study of inhibition mechanisms in the human brain and significantly contribute to our current understanding of numerical cognition's biological bases
A Strobilanthes (Acanthaceae) miscellany
No full textThis paper presents miscellaneous, previously unpublished results arising from the authors’ research into Strobilanthes. S. moylaniae J.R.I.Wood & Scotland from New Guinea and S. dengii J.R.I.Wood & Scotland from Sumatra are proposed as new species, while an unnamed species is described from Sumba Island in Indonesia in the hope that it might be rediscovered. A new subspecies, subsp. subovata J.R.I.Wood & Scotland is described for S. timorensis Nees, while attention is drawn to its plietesial flowering pattern. The new combinations S. benculensis (Bremek.) J.R.I.Wood & Scotland, S. wetarensis (Bremek.) J.R.I.Wood & Scotland, S. javanica (Bremek.) J.R.I.Wood & Scotland and S. serpens (Nees) J.R.I. Wood & Scotland are made. Typification is clarified and where appropriate lectotypes are designated for Hemigraphis hispidula Craib, Lepidagathis setigera Blume, Ruellia crispa L., R. sabiniana Lindl., Strobilanthes duclouxii Benoist, S. erecta C.B.Clarke, S. flava Kurz, S. forrestii Diels, S. scabra Nees, S. secunda T.Anderson and S. thomsonii T.Anderson
Azithromycin versus standard care in patients with mild-to-moderate COVID-19 (ATOMIC2): an open-label, randomised trial
No full textBackground
The antibacterial, anti-inflammatory, and antiviral properties of azithromycin suggest therapeutic potential against COVID-19. Randomised data in mild-to-moderate disease are not available. We assessed whether azithromycin is effective in reducing hospital admission in patients with mild-to-moderate COVID-19.
Methods
This prospective, open-label, randomised superiority trial was done at 19 hospitals in the UK. We enrolled adults aged at least 18 years presenting to hospitals with clinically diagnosed, highly probable or confirmed COVID-19 infection, with fewer than 14 days of symptoms, who were considered suitable for initial ambulatory management. Patients were randomly assigned (1:1) to azithromycin (500 mg once daily orally for 14 days) plus standard care or to standard care alone. The primary outcome was death or hospital admission from any cause over the 28 days from randomisation. The primary and safety outcomes were assessed according to the intention-to-treat principle. This trial is registered at ClinicalTrials.gov (NCT04381962) and recruitment is closed.
Findings
298 participants were enrolled from June 3, 2020, to Jan 29, 2021. Three participants withdrew consent and requested removal of all data, and three further participants withdrew consent after randomisation, thus, the primary outcome was assessed in 292 participants (145 in the azithromycin group and 147 in the standard care group). The mean age of the participants was 45·9 years (SD 14·9). 15 (10%) participants in the azithromycin group and 17 (12%) in the standard care group were admitted to hospital or died during the study (adjusted OR 0·91 [95% CI 0·43–1·92], p=0·80). No serious adverse events were reported.
Interpretation
In patients with mild-to-moderate COVID-19 managed without hospital admission, adding azithromycin to standard care treatment did not reduce the risk of subsequent hospital admission or death. Our findings do not support the use of azithromycin in patients with mild-to-moderate COVID-19.
Funding
National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford and Pfizer
UneVEn: Universal value exploration for multi-agent reinforcement learning
No full textVDN and QMIX are two popular value-based algorithms for cooperative MARL that learn a centralized action value function as a monotonic mixing of per-agent utilities. While this enables easy decentralization of the learned policy, the restricted joint action value function can prevent them from solving tasks that require significant coordination between agents at a given timestep. We show that this problem can be overcome by improving the joint exploration of all agents during training. Specifically, we propose a novel MARL approach called Universal Value Exploration (UneVEn) that learns a set of related tasks simultaneously with a linear decomposition of universal successor features. With the policies of already solved related tasks, the joint exploration process of all agents can be improved to help them achieve better coordination. Empirical results on a set of exploration games, challenging cooperative predator-prey tasks requiring significant coordination among agents, and StarCraft II micromanagement benchmarks show that UneVEn can solve tasks where other state-of-the-art MARL methods fail
From Macro to Micro: a combined bioluminescence‐fluorescence approach to monitor bacterial localization
No full textBacterial bioluminescence is widely used to study the spatiotemporal dynamics of bacterial populations and gene expression in vivo at a population level, but cannot easily be used to study bacterial activity at the level of individual cells. In this study we describe the development of a new library of mini‐Tn7‐lux and lux::eyfp reporter constructs that provide a wide range of lux expression levels, and which combine the advantages of both bacterial bioluminescence and fluorescent proteins to bridge the gap between macro‐ and micro‐scale imaging techniques. We demonstrate that a dual bioluminescence‐fluorescence approach using the lux operon and eYFP can be used to monitor bacterial movement in plants both macro‐ and microscopically, and demonstrate that Pseudomonas syringae pv phaseolicola can colonise the leaf vascular system and systemically infect leaves of common bean (Phaseolus vulgaris). We also show that bacterial bioluminescence can be used to study the impact of plant immune responses on bacterial multiplication, viability and spread within plant tissues. The constructs and approach described in this study can be used to study the spatiotemporal dynamics of bacterial colonisation and to link population dynamics and cellular interactions in a wide range of biological contexts
Solutions to the σk -Loewner-Nirenberg problem on annuli are locally Lipschitz and not differentiable
No full textWe show for k ≥ 2 that the locally Lipschitz viscosity solution to the σkLoewner-Nirenberg problem on a given annulus {a < |x| < b} is C
1,
1
k
loc in each
of {a < |x| ≤ √
ab} and {
√
ab ≤ |x| < b} and has a jump in radial derivative
across |x| =
√
ab. Furthermore, the solution is not C
1,γ
loc for any γ > 1
k
. Optimal
regularity for solutions to the σk-Yamabe problem on annuli with finite constant
boundary values is also established
Host restriction, pathogenesis and chronic carriage of typhoidal Salmonella
No full textWhile conjugate vaccines against typhoid fever have recently been recommended by the World Health Organization for deployment, the lack of a vaccine against paratyphoid, multidrug resistance and chronic carriage all present challenges for the elimination of enteric fever. In the past decade, the development of in vitro and human challenge models has resulted in major advances in our understanding of enteric fever pathogenesis. In this review, we summarise these advances, outlining mechanisms of host restriction, intestinal invasion, interactions with innate immunity and chronic carriage, and discuss how this knowledge may progress future vaccines and antimicrobials
In situ x-ray tomography characterisation of 3D deformation of C/C-SiC composites loaded under tension
No full textC/C-SiC composites fabricated through Liquid Silicon Infiltration were tested under monotonic tension with in situ X-ray computed tomography. The specimens had different fibre orientations with respect to the tensile direction, 0°/90° and ±45°, such that the tension accounted for in-axis and off-axis loads, respectively. The 3D XCT images provided explicit visualisations and quantitative measurements of the distributions of SiC-Si and the orientations of the C fibre bundles. The full-field displacement and strain fields were measured by Digital Volume Correlation, observing a difference in the local deformations in response to the in-axis and off-axis loading. In both specimens, the tensile load triggered significant strain localisations at low stress (<50 MPa). Strong local deformations, observed at both low and high applied stresses, were mostly in the through-thickness direction, indicating local delamination. These observations show the importance of residual stresses to damage development in C/C-SiC composites