1. Harmful algal blooms are increasing in both severity and frequency across the globe. Many bloom-forming species are capable of vertical motility and colony formation. The cyanobacterium Microcystis aeruginosa is a common example of such a species, yet current models poorly predict vertical distributions of M. aeruginosa. 2. To couple the hydrodynamics, buoyancy, and the colony dynamics of Microcystis, we present a system of one-dimensional advection-diffusion-aggregation equations with Smoluchowski aggregation terms. 3. Results indicate Smoluchowski aggregation accurately describes the colony dynamics of M. aeruginosa. Further, transport dynamics are strongly dependent on colony size, and aggregation processes are highly sensitive to algal concentration and wind-induced mixing. Both of these findings have direct consequences to harmful algal bloom formation. 4. While the theoretical framework outlined in this manuscript was derived for M. aeruginosa, both motility and colony formation are common among bloom-forming algae. As such, this coupling of vertical transport and colony dynamics is a useful step for improving forecasts of surface harmful algal blooms.

In this paper, we investigate the stability and bifurcation of a discrete-time prey-predator system which is subject to an Allee effect on prey population. It is concluded that the system undergoes flip and Neimark- Sacker bifurcations in a small neigborhood of the unique positive fixed point which depends on the number of prey-predator. The chaotic behavior that emerges with Neimark-Sacker bifurcation is controlled by the OGY method and hybrid control method. Moreover, the numerical simulations are done to demonsrate the theoratical results.

Aim: The effect of the Dutch nationwide adjustment of reduced 6-TGN target values (from 600-1200 pmol/8x108 RBC to 320-630 pmol/8x108 RBC) on toxicity and clinical outcome of thiopurine treatment in patients with inflammatory bowel disease (IBD) has not yet been established. Therefore the authors determined the incidence of toxicity-induced discontinuations and efficacy at both target concentrations. Methods: This retrospective study was performed in IBD patients treated with azathioprine or mercaptopurine. Two groups were defined: the former target (FT) group with target concentrations of 600-1200 pmol/8x10^8 RBC and the adjusted target (AT) group with target concentrations of 320-630 pmol/8x10^8 RBC. Patients were followed for maximum 52 weeks or until discontinuation of thiopurine therapy. Data were collected from the local hospital electronic health software of Rijnstate Hospital. Results: 151 patients were included, 76 in the FT group and 75 in the AT group. At week 52, 100 out of 150 patients (66%) of the total population discontinued thiopurine therapy. Forty-eight of this discontinuations were due toxicity (48%). The estimated cumulative incidence of toxicity was higher in the FT group compared to the AT group (47% and 35% respectively, p=0.25). No loss of efficacy was seen in the AT group. Conclusion: Reduction of the target range may lead to less toxicity induced discontinuations. In addition, this study did not find any indication that the reduction of the target range diminished efficacy.

Building on the work in [1], this paper shows how Conformal Geometric Algebra (CGA) can be used to model an arbitrary two-port scattering matrix as a rotation in four dimensional Minkowski space, known as a spinor. This spinor model plays the role of the wave-cascading matrix in conventional microwave network theory. Techniques to translate two-port scattering matrix in and out of spinor form are given. Once the translation is laid out, geometric interpretations are given to the physical properties of reciprocity, loss, and symmetry and some mathe- matical groups are identified. Methods to decompose a network into various sub-networks, are given. An example application of interpolating a 2-port network is provided demonstrating an advantage of the spinor model. Since rotations in four dimensional Minkowski space are Lorentz transformations, this model opens up the field of network theory to physicists familiar with relativity, and vice versa.

Tristan Boam1, Bethan G Rogoyski2, Melissa Gabriel3, Paul D Losty4Department of Paediatric Surgery, Leicester Royal Infirmary, Leicester, UKLeicester School of Allied Health Sciences, De Montfort University, Leicester, UKDepartment of Urology, Norfolk and Norwich Hospital, Norwich, UKAlder Hey Children’s Hospital NHS Foundation Trust, School of Health and Life Science, University of Liverpool, UK

Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors in childhood. Cancer predisposition syndromes (CPS) are increasingly recognized as the underlying cause for a number of pediatric malignancies and up to 40% of PPGL are currently thought to be associated with a hereditary predisposition1,2. With the increasingly widespread availability of functional molecular imaging techniques, nuclear medicine imaging modalities such as 18F-FDG-PET/CT, 123I-MIBG SPECT/CT, and 68Ga-DOTATATE PET/CT now play an essential role in the staging, response assessment and determination of suitability for targeted radiotherapy in patients with PPGL. Each of these imaging modalities targets a different cellular characteristic, such as glucose metabolism (FDG), norepinephrine transporter expression (MIBG), or somatostatin receptor expression (DOTATATE), and therefore can be complementary to anatomic imaging and to each other. Given the recent FDA approval3 and increasing use of 68Ga-DOTATATE for imaging in children4, the purpose of this article is to use a case-based approach to highlight both the advantages and limitations of DOTATATE imaging as it compares to current radiologic imaging techniques in the staging and response assessment of pediatric PPGL, and to offer a decision algorithm for the use of functional imaging that can be applied to PPGL, as well as other neuroendocrine malignancies.

We study the role of symmetries in control systems by means of geometric algebra approach. We discuss two specific control problems on Carnot group of step 2 invariant with respect to the action of$SO(3). We understand geodesics as curves in suitable geometric algebras which allows us to asses an efficient algorithm for local control.

In this paper, we consider the Cauchy problem of the compressible quantum Navier-Stokes equations with damping in R3. We first assume that the H3-norm of the initial data is sufficiently small while the higher derivative can be arbitrarily large, and prove the global existence of smooth solutions. Then the decay estimate of the solution is derived for the initial data in a homogeneous Sobolev space or Besov space with negative exponent. In addition, the usual Lp−L2(1 ≤ p ≤ 2) type decay rate is obtained without assuming that the Lpnorm of the initial data is sufficiently small.

In this study, a combined low and high cycle fatigue (CCF) life prediction model, which considers the crack closure effect (CCE) of micro-defects, is proposed based on the continuous damage mechanics. The CCF life prediction model is decomposed into three sub-models: the low cycle fatigue (LCF), high cycle fatigue (HCF) under the maximum stress of LCF (HCFLM), and their coupled damage models. The CCE is considered by taking one CCE parameter into the HCFLM sub-model. The experimental CCF data of K403 full-scale turbine blades under different vibration stresses is used to verify the accuracy of the proposed model to compare with other life prediction models. The prediction life from the proposed model falls within the 2 times of scatter band compared with the experimental results. Further, there are the different damage evolution forms at different vibration stresses. When the vibration stress is below 64.48MPa, the CCF damage mainly is caused by the LCF damage. However, while the vibration stress is higher than 64.48MPa, the HCFLM damage plays a major role in the CCF damage accumulation, and it is predicted that the CCF damage of the first stage serration on the K403 turbine blades is mainly from LCF.

Three-dimensional (3D) bioprinting shows great potential for autologous vascular grafts due to its simplicity, accuracy, and flexibility. 6mm diameter vascular grafts are used in clinic. However, producing small-diameter vascular grafts are still an enormous challenge. Normally, sacrificial hydrogels are used as temporary lumen support to mold tubular structure which will affect the structure’s stability. In this study, we develop a new bioprinting approach to fabricating small-diameter vessel using two-step crosslinking process. ¼ lumen wall of bioprinted gelatin mechacrylate (GelMA) flat structure is exposed to ultraviolet (UV) light briefly for having certain strength, while ¾ lumen wall shows as concave structure remained uncrosslinked. Pre-crosslinked flat structure is merged towards the uncrosslinked concave structure. Two individual structures will be combined tightly into an intact tubular structure by receiving more UV exposure time. Complicated tubular structures are constructed by these method. Notably, the GelMA-based bioink loaded with smooth muscle cells (SMCs) are bioprinted as the outer layer and human umbilical vein endothelial cells (HUVECs) are seeded onto the inner surface. A bionic vascular vessel with dual layers is fabricated successfully and keeps good viability, and functionality. This study may provide a novel idea for fabricating biomimetic vascular network or other more complicated organs.

Title: Food protein-induced enterocolitis syndrome caused by scallopAuthors: Yuka Okura, Yutaka Takahashi, and Ichiro Kobayashi.Institutional affiliation: Department of Pediatrics, KKR Sapporo Medical Center, Sapporo, JapanRunning title: FPIES caused by scallopCorresponding author: Yuka Okura, KKR Sapporo Medical Center, Department of Pediatrics, 6-3-40, Hiragishi 1-jo, Toyohira-ku, Sapporo, 062-0931, JapanPhone: 81-11-822-1811; Facsimile: 81-11-841-4572; E-mail; okura@kkr-smc.comWord count: 973 wordsTables: 0Figures: 0

A document by Laura Sonneveld. Click on the document to view its contents.

Tocilizumab for reduction of mortality in severe COVID-19 patients: how should we GRADE it?Vladimir TrkuljaVladimir Trkulja, MD, PhDDepartment of PharmacologyZagreb University School of MedicineŠalata 1110000 Zagreb, Croatiae-mail: vladimir.trkulja@mef.hrNumber of words: 799Number of figures/tables: 1To the Editor,A recent systematic review/meta-analysis 1 of randomized trials (RCTs) of tocilizumab (plus standard of care [SoC] vs. SoC w/wo placebo) in severe COVID-19 patients was a pleasure to read owing to a clear presentation of a thorough approach to data (e.g., sensitivity analyses, accounting for corticosteroid use, need for mechanical ventilation [MV] at baseline). Authors assigned high quality (certainty) GRADE levels to the evidence of efficacy in reduction of mortality overall (10 RCTs) and in patients without MV at baseline (data from 9 RCTs), and reduction of incident MV (10 RCTs). The grading was based on fixed-effect pooling, likely owing to low inconsistency index (I2) and closely similar fixed-effect and random-effects estimates1. It is this point that deserves a few comments. Conceptually, fixed-effect meta-analysis of RCTs in medicine is rarely justified, since the underlying assumption is practically inevitably violated due to variety of elements contributing to clinical heterogeneity2. The authors1 presented a range of differences in trial designs (e.g., one or repeated tocilizumab dose, more or less use of concomitant corticosteroids, differences in proportion of subjects on MV). When variance across trials is low, fixed and random-effects estimates are numerically close/identical, but the conceptual differences remain. Again, conceptually, the random-effects method is a preferred approach2 (regardless of numerical closeness of fixed/random estimates) and the choice (fixed/random) should not be based on the heterogeneity estimates2. At this point, the issue of the choice of the variance (τ2) estimator should be mentioned. A number of estimators have been explored: performance depends on the nature of the outcome, may vary across trial sizes, depends on the differences in size of included trials, and is problematic when the number of studies is lowe.g.,2-5. Variance reflects on the assigned trial weights and measures of uncertainty about the pooled estimate. While no τ2 estimator is ideal 2-5, it has been suggested that the Paule-Mandel (PM) estimator performs better than the common DerSimonian-Laird estimator for binary outcomes3.Another point to consider is the method to calculate confidence intervals (CIs) around the pooled estimate. While not without certain limitations 6, the Hartung-Knapp-Sidik-Jonkman (HKSJ) method has been repeatedly shown (under variety of scenarios) to result in more adequate coverage probability than the standard method4,7. Figure 1A re-creates meta-analysis (data presented by the authors1) on mortality across the 10 RCTs (all subjects) – it is only that it uses PM variance estimator and HKSJ correction: random-effects estimate suggests that the mean of the distribution of the effects is 0.88 (as reported1), but the CIs extend to 1.04, suggesting that it includes also effects that are somewhat above unity. It also provides prediction intervals (wider) - the best illustration of heterogeneity2,8. When viewed from the present standpoint, data indicate a non-trivial level of imprecision and heterogeneity. The authors themselves reported apparent differences (mortality reduction vs. no reduction) between estimates based on RCTs with a high proportion vs. low proportion of patients concomitantly treated with corticosteroids 1(or those generated accounting only for corticosteroid-treated vs. not treated patients, but such data were very scarce1): so, there is apparent inconsistency of the estimates across clinical settings. As re-created in Figure 1B-C, there was a tendency of reduced mortality in trials with a high proportion of patients co-treated with corticosteroids (corticosteroid treatment regimen likely variable), but with quite some imprecision and heterogeneity; and no such tendency with “low corticosteroid use”. Similarly, in patients not on MV at baseline, there was a consistent reduction in mortality risk across trials with a high proportion of steroid co-treated patients, but not in trials with a low proportion of co-treated patients (Figure 1D-E). There was also a consistent reduction of risk of incident MV in trials with a high proportion of corticosteroid co-treated patients (Figure 1F), whereas the estimate in trials with “low steroid use” is burdened with heterogeneity and imprecision (Figure 1G).Considering the above, if one were to assign a GRADE level9 to evidence of benefit of tocilizumab in severe COVID-19 patients based on the 10 RCTs addressed in the published meta-analysis1, then the following seems reasonable: a) considering (indiscriminately) all 10 RCTs (and all patients), certainty about reduced mortality is closer to “low/moderate” then to “high” due to imprecision (CIs 0.75-1.04) and heterogeneity/inconsistency; b) data on the effect of tocilizumab+corticosteroid combination that could be extracted from the 10 RCTs are scarce. Trials with high vs. low concomitant use of corticosteroids could be perceived as a proxy, but this is indirect, suggestive and not conclusive evidence. Therefore, while the effects of tocilizumab on the risk of incident MV and mortality in patients not on MV at baseline in trials with a high proportion of corticosteroid co-treated patients were consistent and reasonably precisely estimated, certainty about the benefit of tocilizumab (on top of corticosteroids; regimen?) in this setting is at best moderate/low.ReferencesVela D, Vela-Gaxha Z, Rexhepi M, Olloni R, Hyseni V, nallbani R. Efficacy and safety of tocilizumab versus standard of care/placebo in patients with COVID-19; a systematic review and meta-analysis of randomized controlled trials. Br J Clin Pharmacol . 2021; doi: 10.1111/bcp.15124.Higgins JPT, Thomson SG, Spiegelhalter DJ. A re-evaluation of random-effects meta-analysis. J R Statist Soc A . 2009; 172(Pt1):137-159.Veroniki AA, Jackson D, Viechtbauer W, Bender R, Bowden J, Knapp G, Kuss O, Higgins JPT, Langan D, Salanti G. Methods to estimate the between-study variance and its uncertainty in meta-analysis. Res Synth Methods . 2016;7(1): 55-79.Langan D, Higgins JPT, Jakson D, Bowden J. Veroniki AA, Kontopantelis E, Viechtbauer W, Simmonds M. A comparison of heterogeneity variance estimators in simulated random-effects meta-analyses. Res Synth Methods. 2019; 10(1):83-98.IntHout J, Ioannidis JPA, Borm GF, Goeman JJ. Small studies are more heterogeneous than large ones: a meta-meta-analysis. J Clin Epidemiol . 2015; 68(8):860-869.Jakson D, Law M, Rucker G, Schwarzer G. The Hartung-Knapp modification for random-effects meta-analysis: a useful refinement but are there any residual concerns? Stat Med . 2017; 36(25):3923-3934.IntHout J, Ioannidis JPA, Borm GF. The Hartung-Knapp-Sidik-Jonkman method for random effects meta-analysis is straightforward and considerably outperforms the standard DerSimonian-Laird method.BMC Med Res Methodol . 2014; 14:25 doi:10.1186/1471-2288-14-25.IntHout J, Ioannidis JPA, Rovers MM, Goeman JJ. Plea for routinely presenting prediction intervals in meta-analysis. BMJ Open . 2016; 6:e010247 doi: 10.1136/bmjopen-2015-010247Guyatt GH, Oxman, AD, Vist GE, Kurz R, Falck-Ytter Y, Schunemann HJ. GRADE: what is “quality of evidence” and why is it important to clinicians. BMJ . 2008;336(7651):995-998.Balduzzi S, Rucker G, Schwarzer G. How to perform a meta-analysis with R: a practical tutorial. Evid Based Ment Health . 2019; 22(4):153-160.Figure 1 . Re-creation of the published meta-analysis1 using data provided in the published figures: the difference is in that the present estimates are generated using the Paule-Mandel variance estimator (Q-profile method for variance estimate confidence intervals) instead of the DerSimonian-Laired method available in the RevMan software used by the authors1, and Hartung Knapp Sidik Jonkman correction for random effects (see text for explanation). Panel A corresponds to published1Figure 1, panels B and C correspond to published1supplemental Figure S4. Published meta-analysis1 does not include figures that would correspond to panels D-G. Panels E and G are reduced to summaries for brevity. Note that in all meta-analyses point-estimates of I2 and τ2 were low, but the upper limits of their confidence intervals were rather high, particularly when only 4 RCTs were included (except in panel F with highly consistent results across trials). “High%” or “low %” steroid use refers to trials (as presented in the published meta-analysis1) in which >50% or <50% of the patients were co-treated with corticosteroids. Meta-analyses were performed using packagemeta 10 in R.MV – mechanical ventilation; RCT – randomized controlled trial; SoC – standard of care

From an interfacial phenomena standpoint, the effect of length of alkyl chain was evaluated on activities of gallic acid and its alkyl ester derivatives in supramolecular oxidation of stripped soybean oil. The gallic acid molecules (log P = -0.47) with an electron-donating carboxylate anion had a higher scavenging activity against DPPH• than alkyl gallates. Interfacial activities of gallates in emulsion and bulk oil improved as the lengths of the alkyl chain were reached until a critical chain length; after that, further chain length extension causes a decrease in potency. In β-carotene bleaching and Rancimat assays higher inhibitory effect was observed for dodecyl and propyl gallate, respectively. Evaluation of interfacial tension, water content, and droplet size of hydroperoxides reverse micelles in parallel with lipid peroxidation indicated that the inhibitory effect of the alkyl gallates, especially methyl gallate, was significantly better than the gallic acid in the bulk phase oil.

Background: The role of intra-operative parathyroid hormone (IOPTH) monitoring during parathyroidectomy for primary hyperparathyroidism has long been debated. Objectives: Our main goal was to investigate the cure rates of parathyroidectomy for primary hyperparathyroidism with and without IOPTH monitoring. Our secondary goal was to investigate if operating room time can be saved when not using IOPTH monitoring. Design: A retrospective analysis of patients who underwent parathyroidectomy for PHPT for a single adenoma between 2004-2019 was performed. Cure rates and operating room time were compared. Results: 423 patients were included. IOPTH was used in 248 patients (59%). Four patients were not cured, two from each group, with no significant difference between the groups (98.8% vs. 99.1%, p=0.725). Surgery time was significantly longer in the IOPTH group, p<0.001. Conclusions: There is no advantage for using IOPTH during parathyroidectomy in suitable clinical setting. A focused procedure may be safely performed without IOPTH while achieving non-inferior success rates and reducing operative time.

Objectives: We aimed to characterise the use of tracheostomy procedures for all COVID-19 critical care patients in England and to understand how patient factors and timing of tracheostomy affected outcomes. Design: A retrospective observational study using exploratory analysis of hospital administrative data. Setting: All 500 National Health Service hospitals in England. Participants: All hospitalised COVID-19 patients aged ≥ 18 years in England between March 1st and October 31st, 2020 were included. Main outcomes and measures: This was a retrospective exploratory analysis using the Hospital Episode Statistics administrative dataset. Multilevel modelling was used to explore the relationship between demographic factors, comorbidity and use of tracheostomy and the association between tracheostomy use, tracheostomy timing and the outcomes. Results: In total, 2,200 hospitalised COVID-19 patients had a tracheostomy. Tracheostomy utilisation varied substantially across the study period, peaking in April-June 2020. In multivariable modelling, for those admitted to critical care, tracheostomy was most common in those aged 40-79 years, in males and in people of Black and Asian ethnic groups and those with a history of cerebrovascular disease. In critical care patients, tracheostomy was associated with lower odds of mortality (OR: 0.514 (95% CI 0.443 to 0.596), but greater length of stay (OR: 41.143 (95% CI 30.979 to 54.642). In patients that survived, earlier timing of tracheostomy (≤ 14 days post admission to critical care) was significantly associated with shorter length of stay. Conclusions: Tracheostomy is safe and advantageous for critical care COVID-19 patients. Early tracheostomy may be associated with better outcomes, such as shorter length of stay, compared to late tracheostomy.

A document by Ron Ragusa. Click on the document to view its contents.

Radiation Recall Phenomenon (RRP) is an inflammatory process in the site of irradiation, induced by physical and medical agents. Few cases of RRP in the skin and lung have been reported after COVID-19 vaccination. Here, we report radiation recall dermatitis after both doses of inactivated SARS-CoV-2 vaccine (Sinopharm, China).

In the present article, we dene a new kind of the modified Bernstein-Kantorovich operators defined by ¨ Ozarslan (https://doi.org/10.1080/01630563.2015.1079219) i.e. we introduce a new function ς(x) in the modified Bernstein-Kantorovich operators defined by Ozarslan with the property ({) is an infinitely differentiable function on [0; 1]; ς(0) = 0; ς(1) = 1 and ς’(x) > 0 for all x∈ [0; 1]. We substantiate an approximation theorem by using of the Bohman-Korovkins type theorem and scrutinize the rate of convergence with the aid of modulus of continuity, Lipschitz type functions for the our operators and the rate of convergence of functions by means of derivatives of bounded variation are also studied. We study an approximation theorem with the help of Bohman-Korovkins type theorem in A-Statistical convergence. Lastly, by means of a numerical example, we illustrate the convergence of these operators to certain functions through graphs with the help of MATHEMATICA and show that a careful choice of the function ς(x) leads to a better approximation results as compared to the modified Bernstein-Kantorovich operators defined by Ozarslan (https://doi.org/10.1080/01630563.2015.1079219).

Open surgery for chronic type B aortic dissection has been shown to have considerable risks of cerebrovascular complications. Because retrograde perfusion is a potential cause of intraoperative cerebrovascular events, we report our transapical cannulation strategy for descending aorta replacement in chronic type B aortic dissection repair with circulatory arrest. This technique provides an easy and quick establishment of cardiopulmonary bypass by way of a left thoracotomy, and prevention of cerebrovascular event. Transapical cannula can be also used as a vent to ensure a bloodless field during proximal anastomosis and to prevent extension of left ventricle during rewarming. Transapical cannulation is a useful option in open repair of the descending aorta for chronic type B aortic dissection by way of left thoracotomy.

In order to elucidate the temperature-dependent valence state of Ce ion and the occupation number of Ce 4f electrons in cerium mononitride (CeN), we perform an ab initio calculation on CeN by using a many-body scheme combing density functional theory (DFT) with dynamical mean field theory (DMFT), taking into account the spin-orbit coupling (SOC) interaction and on-site Coulomb repulsion between Ce 4f electrons. Results demonstrate that Ce 4f j=5/2 and j=7/2 manifolds undergo insulating-metallic transition with the increasing of temperature. Ce 4f-conduction electrons hybridization, f-f correlation, SOC interaction and final state effects yield a complicated spectrum function in CeN. Ce 4f atomic configuration transition and hybridization might be responsible for the temperature-dependent occupancy number of Ce 4f electrons and the mixed-valence state in CeN. A fact that localization of Ce 4f electrons, i.e., 4f1 configuration or Ce3+ valence, increases with the increasing of temperature could account for the experimentally observed lattice constant versus temperature data. Finally, the so-called quasiparticle band structure is also discussed for comparison with experimental angle-resolved photoemission spectrum (ARPES).

A 3 years old child presented with recurrent chest pain for 3 months, echocardiography showed a thorn inside left ventricle, patient diagnosed as foreign body plus infective endocarditis, received proper treatment, and operation done after inflammatory reaction subsided.

HIV can be associated with cardiovascular complications. We highlight unusual presentation of HIV patient with MI and stroke. 30 year old HIV male presented with MI complicated by stroke. Recovered within 5 days with anti-ischemic and diuretics. Screening tests for unusual presentations prevent fatal complications of common diseases.

Consider a single-electron transistor (SET) with a small size quantum dot (QD), where confined energy and the Coulomb interaction control the charges adding to QD. In this paper, a theoretical analysis of the relation between source-drain voltage and gate voltage has been done to define quantum-Coulomb blocked (and unblocked) diamonds for QD that has N electrons. An analytical equation for the conductance has been derived using the non-equilibrium Green function technique (NEGFT). Further, the effect of QD size and the tunnelling rate on conductance peaks and gaps have been investigated. Finally, the effect of gate voltage on conductance peaks and gaps with respect the quantum-Coulomb blocked regions has been analysed.