An implementation of Deflate in Coq

The widely-used compression format "Deflate" is defined in RFC 1951 and is based on prefix-free codings and backreferences. There are unclear points about the way these codings are specified, and several sources for confusion in the standard. We tried to fix this problem by giving a rigorous mathematical specification, which we formalized in Coq. We produced a verified implementation in Coq which achieves competitive performance on inputs of several megabytes. In this paper we present the several parts of our implementation: a fully verified implementation of canonical prefix-free codings, which can be used in other compression formats as well, and an elegant formalism for specifying sophisticated formats, which we used to implement both a compression and decompression algorithm in Coq which we formally prove inverse to each other -- the first time this has been achieved to our knowledge. The compatibility to other Deflate implementations can be shown empirically. We furthermore discuss some of the difficulties, specifically regarding memory and runtime requirements, and our approaches to overcome them

Evolution of substrate-specific gene expression and RNA editing in brown rot wood-decaying fungi.

Fungi that decay wood have characteristic associations with certain tree species, but the mechanistic bases for these associations are poorly understood. We studied substrate-specific gene expression and RNA editing in six species of wood-decaying fungi from the 'Antrodia clade' (Polyporales, Agaricomycetes) on three different wood substrates (pine, spruce, and aspen) in submerged cultures. We identified dozens to hundreds of substrate-biased genes (i.e., genes that are significantly upregulated in one substrate relative to the other two substrates) in each species, and these biased genes are correlated with their host ranges. Evolution of substrate-biased genes is associated with gene family expansion, gain and loss of genes, and variation in cis- and trans- regulatory elements, rather than changes in protein coding sequences. We also demonstrated widespread RNA editing events in the Antrodia clade, which differ from those observed in the Ascomycota in their distribution, substitution types, and the genomic environment. Moreover, we found that substrates could affect editing positions and frequency, including editing events occurring in mRNA transcribed from wood-decay-related genes. This work shows the extent to which gene expression and RNA editing differ among species and substrates, and provides clues into mechanisms by which wood-decaying fungi may adapt to different hosts

Hidden breakpoints in genome alignments

During the course of evolution, an organism's genome can undergo changes that affect the large-scale structure of the genome. These changes include gene gain, loss, duplication, chromosome fusion, fission, and rearrangement. When gene gain and loss occurs in addition to other types of rearrangement, breakpoints of rearrangement can exist that are only detectable by comparison of three or more genomes. An arbitrarily large number of these "hidden" breakpoints can exist among genomes that exhibit no rearrangements in pairwise comparisons. We present an extension of the multichromosomal breakpoint median problem to genomes that have undergone gene gain and loss. We then demonstrate that the median distance among three genomes can be used to calculate a lower bound on the number of hidden breakpoints present. We provide an implementation of this calculation including the median distance, along with some practical improvements on the time complexity of the underlying algorithm. We apply our approach to measure the abundance of hidden breakpoints in simulated data sets under a wide range of evolutionary scenarios. We demonstrate that in simulations the hidden breakpoint counts depend strongly on relative rates of inversion and gene gain/loss. Finally we apply current multiple genome aligners to the simulated genomes, and show that all aligners introduce a high degree of error in hidden breakpoint counts, and that this error grows with evolutionary distance in the simulation. Our results suggest that hidden breakpoint error may be pervasive in genome alignments.Comment: 13 pages, 4 figure

Effect of contact with podiatry in a team approach context on diabetic foot ulcer and lower extremity amputation: systematic review and meta-analysis

Multidisciplinary team (MDT) approach has been shown to reduce diabetic foot ulcerations (DFUs) and lower extremity amputations (LEAs), but there is heterogeneity between team members and interventions. Podiatrists have been suggested as "gatekeepers" for the prevention and management of DFUs. The purpose of our study is to review the effect of podiatric interventions in MDTs on DFUs and LEAs. We conducted a systematic review of available literature. Data's heterogeneity about DFU outcomes made it impossible for us to include it in a meta-analysis, but we identified 12 studies fulfilling inclusion criteria that allowed for them to be included for LEA outcomes. With the exception of one study, all reported favourable outcomes for MDTs that include podiatry. We found statistical significance in favour of an MDT approach including podiatrists for our primary outcome (total LEAs (RR: 0.69, 95% CI 0.54–0.89, I2 = 64%, P = 0.002)) and major LEAs (RR: 0.45, 95% CI 0.23–0.90, I2 = 67%, P < 0.02). Our systematic review, with a standard search strategy, is the first to specifically address the relevant role of podiatrists and their interventions in an MDT approach for DFU management. Our observations support the literature that MDTs including podiatrists have a positive effect on patient outcomes but there is insufficient evidence that MDTs with podiatry management can reduce the risk of LEAs. Our study highlights the necessity for intervention descriptions and role definition in team approach in daily practice and in published literature

Effectiveness of saline water and lidocaine injection treatment of intractable plantar keratoma: a randomised feasibility study

Background: An intractable plantar keratoma (IPK) is a conical thickening of the epidermis' stratum corneum and a common cause of foot pain which can have a significant, detrimental impact on the mobility, quality of life and independence of individuals. Conservative treatments are currently offered to patients with IPK, but they are unsatisfactory since they do not offer a sufficient or permanent reduction of symptoms. The purpose of this study was the evaluation of the feasibility, safety and effectiveness of innovative treatments for intractable plantar keratoma (IPK). Methods: A randomized single blind trial with 40 patients divided with block randomization in four parallel groups was conducted to compare treatment combinations: conservative sharp debridement only or sharp debridement with needle insertion, physiological water injection or lidocaine injection. All patients obtained the same treatment four times at a four-week interval. At each visit, visual analog scale (VAS), Foot Function Index (FFI) and IPK size were evaluated. VAS and FFI were also completed at a six and twelve-month follow-up. Results: Our findings in regards to feasibility demonstrated recruitment challenges because of the anticipated pain that would be provoked by needle insertion may not be worth the potential pain relief compared to debridement alone from the patient's perspective. This was also the principal cause of drop out. Our preliminary results show no main effect of group for any of the clinical outcomes: pain felt on VAS, FFI score, IPK's size (p > 0.05). However, the analysis revealed a statistically significant effect of time on VAS (p 0.05). Conclusions: This study demonstrates that IPK treatment consisting of sharp debridement with needle insertion, physiological saline water injection or lidocaine injection is feasible and safe. There was a non-statistically significant trend toward diminishing pain intensity compared to scalpel debridement alone. The pain provoked by needle insertion and injection treatments must be addressed with a scientifically proven protocol to make it more comfortable for patients before these treatments could be considered in further studies. Trial registration: ClinicalTrials.gov, NCT04777227. 2 March, 2021 - Retrospectively registered (All participants were recruited prior to registration)

Mode identification from monochromatic amplitude and phase variations for the rapidly pulsating subdwarf B star EC 20338-1925

We obtain time-series spectrophotometry observations at the VLT with the aim of partially identifying the dominant oscillation modes in the rapidly pulsating subdwarf B star EC 20338-1925 on the basis of monochromatic amplitude and phase variations. From the data gathered, we detect four previously known pulsations with periods near 147, 168, 126 and 140 s and amplitudes between 0.2 and 2.3 % of the star's mean brightness. We also determine the atmospheric parameters of EC 20338-1925 by fitting our non-LTE model atmospheres to an averaged combined spectrum. The inferred parameters are Teff = 34,153+-94 K, log g =5.966+-0.017 and log[N(He)/N(H)] = - 1.642+-0.022, where the uncertainty estimates quoted refer to the formal fitting errors. Finally, we calculate the observed monochromatic amplitudes and phases for the periodicities extracted using least-squares fitting to the light curves obtained for each wavelength bin. These observed quantities are then compared to the corresponding theoretical values computed on the basis of dedicated model atmosphere codes and also taking into account non-adiabatic effects. We find that the quality of the data is sufficient to identify the dominant pulsation at 146.9 s as a radial mode, while two of the lower amplitude periodicities must be low-degree modes with l=0-2. This is the first time that monochromatic amplitudes and phases have been used for mode identification in a subdwarf B star, and the results are highly encouraging.Comment: 11 pages. Accepted for publication in Astronomy & Astrophysic

Outcomes of hallux amputation versus partial first ray resection in people with non-healing diabetic foot ulcers: A pragmatic observational cohort study

There are few data comparing outcomes after hallux amputation or partial first ray resection after diabetic foot ulcer (DFU). In a similar context, the choice to perform one of these two surgeries is attributable to clinician preference based on experience and characteristics of the patient and the DFU. Therefore, the purpose of this study was to determine the more definitive surgery between hallux amputation and partial first ray resection. We abstracted data from a cohort of 70 patients followed for a 1-year postoperative period to support clinical practice. We also attempted to identify patient characteristics leading to these outcomes. Our results suggested no statistical difference between the type of surgery and outcomes such as recurrence of DFU and amputation at 3, 6, and 12 months or death. However, there was a statistically significantly increased likelihood of re-ulceration for patients with CAD who underwent hallux amputation (p = 0.02). There was also a significantly increased likelihood of re-ulceration for people with depression or a history when the partial ray resection was performed (p = 0.02). Patients with prior amputation showed a higher probability of undergoing another re-amputation with partial ray resection (p = 0.01). Although the trends that emerge from this project are limited to what is observed in this statistical context, where the number of patients included and the number of total observations per outcome were limited, it highlights interesting data for future research to inform clinical decisions to support best practices for the benefit of patients