The maximum clique enumeration problem: algorithms, applications, and implementations

Background The maximum clique enumeration (MCE) problem asks that we identify all maximum cliques in a finite, simple graph. MCE is closely related to two other well-known and widely-studied problems: the maximum clique optimization problem, which asks us to determine the size of a largest clique, and the maximal clique enumeration problem, which asks that we compile a listing of all maximal cliques. Naturally, these three problems are View MathML /\u3e-hard, given that they subsume the classic version of the View MathML /\u3e-complete clique decision problem. MCE can be solved in principle with standard enumeration methods due to Bron, Kerbosch, Kose and others. Unfortunately, these techniques are ill-suited to graphs encountered in our applications. We must solve MCE on instances deeply seeded in data mining and computational biology, where high-throughput data capture often creates graphs of extreme size and density. MCE can also be solved in principle using more modern algorithms based in part on vertex cover and the theory of fixed-parameter tractability (FPT). While FPT is an improvement, these algorithms too can fail to scale sufficiently well as the sizes and densities of our datasets grow. Results An extensive testbed of benchmark graphs are created using publicly available transcriptomic datasets from the Gene Expression Omnibus (GEO). Empirical testing reveals crucial but latent features of such high-throughput biological data. In turn, it is shown that these features distinguish real data from random data intended to reproduce salient topological features. In particular, with real data there tends to be an unusually high degree of maximum clique overlap. Armed with this knowledge, novel decomposition strategies are tuned to the data and coupled with the best FPT MCE implementations. Conclusions Several algorithmic improvements to MCE are made which progressively decrease the run time on graphs in the testbed. Frequently the final runtime improvement is several orders of magnitude. As a result, instances which were once prohibitively time-consuming to solve are brought into the domain of realistic feasibility

Surgical site infection following surgery for hand trauma: a systematic review and meta-analysis

Surgical site infection is the most common healthcare-associated infection. Surgical site infection after surgery for hand trauma is associated with increased antibiotic prescribing, re-operation, hospital readmission and delayed rehabilitation, and in severe cases may lead to amputation. As the risk of surgical site infection after surgery for hand trauma remains unclear, we performed a systematic review and meta-analysis of all primary studies of hand trauma surgery, including randomized controlled trials, cohort studies, case-control studies and case series. A total of 8836 abstracts were screened, and 201 full studies with 315,618 patients included. The meta-analysis showed a 10% risk of surgical site infection in randomized control trials, with an overall risk of 5% when all studies were included. These summary statistics can be used clinically for informed consent and shared decision making, and for power calculations for future clinical trials of antimicrobial interventions in hand trauma

Earthworm activity and availability for meadow birds is restricted in intensively managed grasslands

Earthworms are an important prey for the endangered meadow birds of northwest Europe. Although intensive grassland management with high manure inputs generally promotes earthworm abundance, it may reduce the effective food availability for meadow birds through desiccation of the topsoil, which causes earthworms to remain deeper in the soil. We studied the response of Red Worm Lumbricus rubellus, a detritivore, and Grey Worm Aporrectodea caliginosa, a geophage, to soil moisture profiles in the field and under experimental conditions. Surfacing earthworms were counted weekly in eight intensively managed grasslands (treated with high inputs of slurry by slit injection) with variable groundwater tables in the Netherlands. At each count, soil penetration resistance, soil moisture tension and groundwater level were measured, while air temperature and humidity were obtained from a nearby weather station. The response to variation in the vertical distribution of soil moisture was also experimentally studied in the two earthworm species. In the field, earthworms’ surfacing activity at night was negatively associated with soil moisture tension and positively by relative air humidity. Surprisingly, there was no effect of groundwater level; an important management variable in meadow bird conservation. Under experimental conditions, both L. rubellus and A. caliginosa moved to deeper soil layers (&gt;20 cm) in drier soil moisture treatments, avoiding the upper layer when moisture levels dropped below 30%. Synthesis and applications. We propose that in intensively managed grasslands with slurry application, topsoil desiccation reduces earthworm availability for meadow birds. This can be counteracted by keeping soil moisture tensions of the top soil above −15 kPa. We suggest that the late raising of groundwater tables in spring and the disturbance of the soil by slit injection of slurry increase topsoil desiccation. This decreases earthworm availability when it matters most for breeding meadow birds. Meadow bird conservation will benefit from revised manure application strategies that promote earthworm activity near or at the soil surface.</p

Controlling and characterising the deposits from polymer droplets containing microparticles and salt

It is very well known that as suspension droplets evaporate, a pinned contact line leads to strong outwards capillary flow resulting in a robust coffee ring-stain at the periphery of the droplet. Conversely tall pillars are deposited in the centre of the droplet when aqueous droplets of poly(ethylene oxide) evaporate following a boot-strapping process in which the contact line undergoes fast receding, driven by polymer precipitation. Here we map out the phase behaviour of a combined particle-polymer system, illustrating a range of final deposit shapes, from ring-stain to flat deposit to pillar. Deposit topologies are measured using profile images and stylus profilometery, and characterised using the skewness of the profile as a simple analytic method for quantifying the shapes: pillars produce positive skew, flat deposits have zero skew and ring-stains have a negative value. We also demonstrate that pillar formation can be disrupted using potassium sulphate salt solutions, which change the water from a good solvent to a thetapoint solvent, consequently reducing the size of the polymer coils. This inhibits polymer crystallisation, interfering with the bootstrap process and ultimately preventing pillars from forming. Again, the deposit shapes are quantified using the skew parameter

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