This paper is devoted to the study of Tur\’{an} type inequalities for some well-known special functions such as supersine and supercosine which are derived by using a new form of the Cauchy-Bunyakovsky-Schwarz inequality.

A recently published approach for modeling the cross flow in an extruder channel using a new solution to the biharmonic equation is utilized in a study of chaotic mixing in a free helix single screw extruder. This novel extruder was designed and constructed with the screw flight, also referred to as the helix, detached from the screw core. Each of the screw elements could be rotated independently to obtain chaotic motion in the screw channel. Using the new extruder, experimental evidence for the increased mixing of a dye, for both a Dirac and droplet input, with a chaotic flow field relative to the traditional residence time distribution is presented. These experimental results are compared using the new biharmonic equation-based model. Because of the ability to periodically rotate only the flight/helix, the chaotic mixing results are minimally confounded by the existence of Moffat eddies.

A document by Shawn Mondoux. Click on the document to view its contents.

Oxford Nanopore Technologies (ONT) is a third-generation sequencing technology that is gaining popularity in ecological research for its portable and low-cost sequencing possibilities. Although the technology is primarily developed for long-read sequencing, it can also be applied to sequence amplicons. The downside of ONT is the low quality of the raw reads. Hence, generating a high-quality consensus sequence is still a challenge. We present Amplicon_sorter, a tool for reference-free sorting of ONT sequenced amplicons based on their similarity in sequence and length and for building solid consensus sequences.

A 75-year-old male presented with an immediately threatened grade IIb acute ischemia of the left leg due to thrombosis of a femoro-infrapopliteal prosthetic bypass graft. After an urgent Computed Tomography Angiography, an urgent graft thrombectomy was performed using a 5 Fr Fogarty catheter, which had a troublesome distal passage.

Background: Cryoballoon (CB) based pulmonary vein isolation (PVI) has proven to be as effective as radiofrequency (RF) based ablation. Different ablation protocols took the individual time-to-isolation (TTI) into account aiming at shorter but equally or even more effective freeze-cycles. The current study sought to assess the impact of the TTI on PVI durability in patients undergoing a repeat procedure for recurrence of atrial tachyarrhythmia (ATA). Methods and Results: In 205 patients with ATA recurrence after previous CB-based PVI a total of 806 PVs were identified. One hundred-twenty-six out of 806 PVs (16%) were previously treated with a TTI guided ablation (protocol #1; TTI+120 sec.), in 92/806 (11%) PVs TTI was only monitored (m) but fixed freeze-cycles were applied (protocol #2; mTTI) and in 588/806 (73%) a fixed freeze-cycle was applied without TTI-monitoring. There was no difference in the PV-reconduction rate between the groups (P=0.23). The right inferior pulmonary vein (RIPV) showed overall significantly higher reconduction rates compared to the other PVs (RIPV – left inferior PV (LIPV) p<0.003, -left superior PV (LSPV) p<0.001, - right superior PV RSPV p<0.013). In 21 patients (10%) only for the RIPV reconduction was assessed. Conclusions: TTI based CB ablation did not show significant differences regarding PV-reconduction rates compared to the other protocols.

Unlike many viral infections such as influenza, and the two previous incarnations of the coronavirus, SARS and MERS, Covid-19 originally appeared to be of similar severity, after adjusting for age, BMI and other co-morbidities, in the pregnant as in the non-pregnant population. Worryingly the paper from the Italian Obstetric Surveillance System COVID-19 Working Group (p …), suggests that, in pregnancy, the virus may be getting more virulent with the advent of newer variants. Specifically the need for ventilation or ICU admission was significantly increased during the second wave (alpha variant predominant) compared to the first (wild-type predominant), albeit with no maternal deaths during the first wave and only one during the second. If real, this is both unexpected and concerning. Unexpected, because viruses tend to mutate in the direction of reduced severity; it is not in the interests of the virus that the host dies. Concerning, because it suggest that the newer variants are behaving more like other viral diseases; causing more severe disease in pregnancy.The evidence from Italy is supported by at least three other sources. In August a preprint from the UK Obstetric Surveillance Service (Vousden et al. MedRxiv 2021.07.22.21261000; doi: https://doi.org/10.1101/2021.07.22.21261000 accessed 30 September) reported disease severity in pregnancy when wild type predominated, when alpha predominated and when delta predominated. In each succeeding phase disease severity in increased. On 24 September the UK Intensive Care National Audit & Research Centre reported (ICNARC 17 September 2021 https://www.icnarc.org/Our-Audit/Audits/Cmp/Reports accessed 30 September) that the absolute numbers of pregnant women admitted to critical care with Covid were significantly higher in the second (alpha) wave than the first (wild type), and looked set to be significantly higher again in the third (delta) wave. Finally a large series from Nair Hospital, the largest hospital caring for Covid in Mumbai (Mahajan et al. Obstet Gynecol: July 7, 2021 doi: 10.1097/AOG.0000000000004529), reported significantly higher maternal mortality during the second (alpha predominant) wave than the first (wild type).The lesson for women is simple, get vaccinated. Vaccines are safe and if the disease is really getting more severe, the balance of risks and benefits will be moving overwhelmingly in favour of vaccination. The lesson for obstetricians is more complicated. Encourage women to get vaccinated and take the disease seriously. Keep women with Covid out of hospital if possible, but monitor them with saturation monitors reliably, so those who deteriorate can be picked up quickly. When they need admission follow evidence-based treatment guidelines, and keep using personal protective equipment. We’re not yet done with Covid.Jim Thornton MD FRCOGEmeritus Professor of Obstetrics & Gynaecology, University of Nottingham.

This study explored the application of a Vertical Electrokinetic system (V-EK) with multilayer electrodes in shallow soil to form an “Electric Sieve” to mitigate and prevent the soil salinization caused by salts rising from shallow groundwater in the coastal areas. In the model V-EK system, the electric resistances of soil column, reversely corresponding to salinity, at the applied voltages 4, 10 and 20 V were 266, 487 and 1272 Ω, respectively. Meanwhile, lower electrical conductivity (EC, between 67-230 μs/cm) were observed in the soil within 50 cm below the surface at the voltages of 10 V and 20 V, which was much lower than the minimum value (581 μs/cm) of the control with no current applied. For the control column without EK treatment (0 V), soil in the surface layer had the highest EC value at 1721 μS/cm due to the salts rising from the bottom, and the EC values of soil beneath the surface were in the range of 581-1127 μS/cm. Compared to control column, the level of ions in the surface soil significantly declined after V-EK treatment, especially for the column with voltage at 10 V and 20V. When voltage was at 20 V, Na+ was detected at a range of 0.06-0.08mg/g in the surface soil, a >99% reduction when compared to the controls. Similar efficacy was observed for chloride (Cl-), in the V-EK column with the voltages at 10 V and 20V.

The amount of data available from genomic medicine has revolutionized the approach to identify the determinants underlying many rare diseases. The task of confirming a genotype-phenotype causality for a patient affected with a rare genetic disease is often challenging. In this context, the establishment of the MatchMaker Exchange (MME) network has assumed a pivotal role in bridging heterogeneous patient information stored on different medical and research servers. MME has made it possible to solve rare disease cases by “matching” the genotypic and phenotypic characteristics of a patient of interest with patient data available at other clinical facilities participating in the network. Here, we present PatientMatcher (https://github.com/Clinical-Genomics/patientMatcher), an open-source Python and MongoDB-based software solution developed by Clinical Genomics facility at the Science for Life Laboratory in Stockholm. PatientMatcher is designed as a standalone MME server, but can easily communicate via REST API with external applications managing genetic analyses and patient data. The MME node is being implemented in clinical production in collaboration with the Genomic Medicine Center Karolinska at the Karolinska University Hospital. PatientMatcher is written to implement the MME API and provides several customizable settings, including a custom-fit similarity score algorithm and adjustable matching results notifications.

Over 7,000 rare genetic diseases have been identified, and millions of newborns are affected by severe rare genetic diseases each year. A variety of Human Phenotype Ontology (HPO)-based clinical decision support systems (CDSS) and patient repositories have been developed to support clinicians in diagnosing patients with suspected rare genetic diseases. In September 2017, we released PubCaseFinder (https://pubcasefinder.dbcls.jp), a web-based CDSS that provides ranked lists of genetic and rare diseases using HPO-based phenotypic similarities, where top-listed diseases represent the most likely differential diagnosis. We also developed a Matchmaker Exchange (MME) application programming interface (API) to query PubCaseFinder, which has been adopted by several patient repositories. In this paper, we describe notable updates regarding PubCaseFinder, the GeneYenta matching algorithm implemented in PubCaseFinder, and the PubCaseFinder API. The updated GeneYenta matching algorithm improves the performance of the CDSS automated differential diagnosis function. Moreover, the updated PubCaseFinder and new API empower patient repositories participating in MME and medical professionals to actively use HPO-based resources.

Vibrio alginolyticus and Vibrio (Aliivibrio) fischeri are Gram-negative bacteria found globally in marine environments. During the past decade, studies have shown that certain Gram-negative bacteria, including Vibrio species (cholerae, parahaemolyticus, and vulnificus) are capable of using exogenous polyunsaturated fatty acids (PUFAs) to modify the phospholipids of their membrane. Moreover, exposure to exogenous PUFAs has been shown to affect certain phenotypes that are important factors of virulence. The purpose of this study was to investigate whether V. alginolyticus and V. fischeri are capable of responding to exogenous PUFAs by remodeling their membrane phospholipids and/or altering behaviors associated with virulence. Thin-layer chromatography (TLC) analyses and ultra-performance liquid chromatography-electrospray ionization mass spectrometry (UPLC/ESI-MS) confirmed incorporation of all PUFAs into membrane phosphatidylglycerol and phosphatidylethanolamine. Several growth phenotypes were identified when individual fatty acids were supplied in minimal media and as sole carbon sources. Interestingly, several PUFAs acids inhibited growth of V. fischeri. Significant alterations to membrane permeability were observed depending on fatty acid supplemented. Strikingly, arachidonic acid (20:4) reduced membrane permeability by approximately 35% in both V. alginolyticus and V. fischeri. Biofilm assays indicated that fatty acid influence was dependent on media composition and temperature. All fatty acids caused decreased swimming motility in V. alginolyticus, while only linoleic acid (18:2) significantly increased swimming motility in V. fischeri. In summary, exogenous fatty acids cause a variety of changes in V. alginolyticus and V. fischeri, thus adding these bacteria to a growing list of Gram-negatives that exhibit versatility in fatty acid utilization and highlighting the potential for environmental PUFAs to influence phenotypes associated with planktonic, beneficial, and pathogenic associations.

Bacillus subtilis is described as a promising production strain for lipopeptides. In the case of B. subtilis strains JABs24 and DSM10T, surfactin, and plipastatin are produced. Lipopeptide formation is controlled, among others, by the DegU response regulator. The activating phospho-transfer by the DegS sensor kinase is stimulated by the pleiotropic regulator DegQ, resulting in enhanced DegU activation. In B. subtilis 168, a point mutation in the degQ promoter region leads to a reduction in gene expression. Corresponding reporter strains showed a 14-fold reduced expression. This effect on degQ expression and the associated impact on lipopeptide formation was examined for B. subtilis JABs24, a lipopeptide-producing derivative of strain 168, and B. subtilis wild-type strain DSM10T, which has a native degQ expression. Based on the stimulatory effects of the DegU regulator on secretory protease formation, the impact of degQ expression on extracellular protease activity was additionally investigated. To follow the impact of degQ, a deletion mutant was constructed for DSM10T, while a natively expressed degQ version was integrated into strain JABs24. This allowed strain-specific quantification of the stimulatory effect of degQ expression on plipastatin and the negative effect on surfactin production in strains JABs24 and DSM10T. While an unaffected degQ expression reduced surfactin production in JABs24 by about 25%, a 6-fold increase in plipastatin was observed. In contrast, degQ deletion in DSM10T increased surfactin titer by 3-fold but decreased plipastatin production by 5-fold. In addition, although significant differences in extracellular protease activity were detected, no decrease in plipastatin and surfactin produced during cultivation was observed.

The human microbiome has begun to emerge as a potential forensic tool, with varied applications ranging from unique identification to investigative leads that link individuals and/or locations. The relative abundance of the combined DNA of the microbiome, compared to human nuclear DNA, may expand potential sources of biological evidence, especially in cases with transfer or low-copy number DNA samples. This work sought to determine the optimal swab type for the collection and analysis of the microbiome. A bacterium (Proteus mirabilis) was deposited by pipette onto four swab types (cotton, flocked, dental applicators, and dissolvable), and extraction and real-time PCR quantitation of the bacterial DNA were performed, which allowed for absolute microbial DNA recovery and comparison of yields across the four sampling substrates. Flocked swabs had the highest yield (~1240 ng) compared to the cotton swabs (~184 ng), dental applicators (~533 ng), and dissolvable swabs (~430 ng). The collection efficiency was further evaluated for cotton and flocked swabs using dried microbial samples spotted onto non-porous surfaces (treated wood, glass, plastic, and tile). Flocked swabs performed consistently better across wood, glass, and tile, but showed decreased recovery from plastic. The cotton swabs failed in the recovery of P. mirabilis DNA across all surfaces. Knowing the appropriate sampling substrate will be useful as others continue to investigate the use of the microbiome as a forensics tool.

In the paper, the author presents three integral representations of extended central binomial coefficient, proves decreasing and increasing properties of two power-exponential functions involving extended (central) binomial coefficients, derives several double inequalities for bounding extended (central) binomial coefficient, and compares with known results.

Process synthesis using rigorous unit operation models is highly desirable to identify the most efficient pathway for sustainable production of fuels and value-added chemicals. However, it often leads to a large-scale strongly nonlinear and nonconvex mixed integer nonlinear programming (MINLP) model. In this work, we propose two robust homotopy continuation enhanced branch and bound (HCBB) algorithms (denoted as HCBB-FP and HCBB-RB) where the homotopy continuation method is employed to gradually approach the optimal solution of the NLP subproblem at a node from the solution at its parent node. A variable step length is adapted to effectively balance feasibility and computational efficiency. The computational results demonstrate that the proposed HCBB algorithms can find the same optimal solution from different initial points, while the existing MINLP algorithms fail or find much worse solutions. In addition, HCBB-RB is superior to HCBB-FP due to lower computational effort required for the same locally optimal solution.

Rationale and aims: Precision medicine (PM) raises a key question: How can we know what works when the number of people with a health problem becomes small or one (n=1)? We here present a formative case from Norway. The Norwegian Board of Health Supervision was faced with a cancer patient, who had improved after treatment with a drug in the private health sector but was refused continued treatment in the public health service due to lack of clinical trial evidence. The Board overturned this decision, arguing that the drug had been unambiguously documented to work in the individual case. We aim to provide an in-depth analysis of this case and The Board´s decision and thereby to illustrate and elucidate key epistemological and ethical issues and developments in PM. Method: We provide our analysis and discussion using tools of critical thinking and concepts from philosophy of science and medicine such as uncertainty, evidence, forms of inference and causation. We also examine the case in the light of the history of evidence-based medicine (EBM). Results and discussion: The case reflects an epistemological shift in medicine where PM puts greater emphasis on evidence that arises in individual patients after the treatment is provided over preexisting population-based evidence. PM may rely more heavily on abduction to decide what works and qualitative, rather than quantitative judgments. The case also illustrates a possible shift in the concept of causation from regularity accounts to mechanistic and process accounts. We discuss ethical implications of a shift from more “traditional” to “personalized EBM”. Conclusion: A framework that is more based on abductions and evidence arising in the individual case has problems in creating quantifiable, reliable, and generalizable evidence, and in promoting transparency and accountability. PM currently lacks clear criteria for deciding what works in an individual, posing ethical challenges.

Temperate phages are bacterial viruses that either reside integrated in a bacterial genome as lysogens or enter a lytic lifecycle. Decision between lifestyles is determined by a switch involving a phage-encoded repressor, CI, and a promoter region from which lytic and lysogenic genes are divergently transcribed. Here we investigate the switch of phage phi13 from the human pathogen Staphylococcus aureus. phi13 encodes several virulence factors and is prevalent in S. aureus strains colonizing humans. We show that the phi13 switch harbors a cI gene, a predicted mor (modulator of repression) gene, and three high-affinity operator sites binding CI. To quantify the decision between lytic and lysogenic lifestyle, we introduced reporter plasmids that carry the 1.3 kb switch region from phi13 with the lytic promoter fused to lacZ into S. aureus and B. subtilis. Analysis of beta-galactosidase expression indicated that decision frequency is independent of host factors. The white “lysogenic” phenotype, which relies on expression of cI, could be switched to a stable blue “lytic” phenotype by DNA damaging agents. We have characterized lifestyle decisions of phage phi13, and our approach may be applied to other temperate phages encoding virulence factors in S. aureus.

We have reported a case of trans-cuff leakage that occurred in a composite graft of bio-Bentall operation. The leakage resolved several months after surgery, similar to the trans-cuff leakage seen in simple aortic valve replacement. We have proposed hypotheses on the mechanism of trans-cuff leakage during a bio-Bentall operation and suggested ways to prevent it from occurring.