Background/objectives: Ataxia Telangiectasia (A-T) is a complex inherited disease that is associated with an increased risk of malignancy. Surveillance guidelines have demonstrated significant health benefits in other cancer predisposition syndromes (CPS). Evidence-based guidelines for cancer screening are not currently used in the UK for people affected by A-T. This study aims to understand how people with A-T and their parents feel about cancer surveillance using whole-body MRI to inform the future development of cancer surveillance guidelines. Design/Methods: We conducted semi-structured interviews of people affected by A-T. Data were analysed inductively using thematic analysis. Results: Nine parents of children with A-T and four adults with A-T were interviewed. Five main themes emerged from the data. All participants viewed cancer screening for children with A-T as invaluable and emphasised the perceived value of early detection. The second theme acknowledged the anxiety associated with cancer and cancer surveillance and the third theme highlighted the perceived limitations around current practice, with the responsibility for monitoring falling too strongly on parents and patients. The fourth theme identified the need for effective preparation for cancer screening, including clear communication, and the challenges of MRI screening were recognised in the fifth theme with specific recommendations made for improving the child’s experience. Conclusion: This study suggests that stakeholders are positive about the perceived advantages of a cancer screening programme. Ongoing support and preparation techniques should be adopted to maximise adherence and minimise adverse psychosocial outcomes.

Background. Studies on the long-term treatment outcomes of childhood acute lymphoblastic leukemia (ALL) in resource-limited countries are scarce. The purpose of this study was to assess the evolution of survival outcomes of pediatric ALL in a tertiary care center in Thailand over a 40-year period. Patients and methods. We retrospectively reviewed the medical records of pediatric patients who were diagnosed with ALL and treated at our center between June 1979 and December 2019. We classified the patients into 4 study periods depending on the therapy protocol used to treat the patients (period 1: 1979-1986, period 2: 1987-2005, period 3: 2006-2013, and period 4: 2014-2019). The Kaplan Meier method was used to determine overall and event-free survival for each group. The log-rank test was used to identify statistical differences. Results. Over the study period, 726 patients with ALL were identified, 428 boys (59%) and 298 girls (41%), with a median age at diagnosis of 4.7 years (range: 0.2–15 years). The study periods 1, 2, 3, and 4 had 5-year event-free survival (EFS) rates of 27.6%, 41.6%, 55.9% and 66.4%, and 5-year overall survival (OS) rates of 32.8%, 47.8%, 61.5%, and 69.3%, respectively. From period 1 to period 4, both the EFS and OS rates increased significantly (p<0.0001). Age, study period, and white blood cell (WBC) count were all significant prognostic indicators for survival outcomes. Conclusions. The overall survival of patients with ALL treated in our center improved significantly over time from 32.8% in period 1 to 69.3% in period 4.

Symbiosis often occurs between partners with distinct life history characteristics and dispersal mechanisms. Many bacterial symbionts have genomes comprised of multiple replicons with distinct rates of evolution and horizontal transmission. Such differences might drive differences in population structure between hosts and symbionts and among the elements of the divided genomes of bacterial symbionts. These differences might, in turn, shape the evolution of symbiotic interactions and bacterial evolution. Here we use whole genome resequencing of a hierarchically-structured sample of 191 strains of Sinorhizobium meliloti collected from 21 locations in southern Europe to characterize population structures of this bacterial symbiont and its host plant Medicago truncatula. Sinorhizobium meliloti genomes showed high local (within-site) variation and little isolation by distance. This was particularly true for the two symbiosis elements pSymA and pSymB, which have population structures that are similar to each other, but distinct from both the bacterial chromosome and the host plant. The differences in population structure may result from among-replicon differences in the extent of horizontal gene transfer, although given limited recombination of the chromosome, different levels of purifying or positive selection may also contribute to among-replicon differences. Discordant population structure between hosts and symbionts indicates that geographically and genetically distinct host populations in different parts of the range might interact with genetically similar symbionts, potentially minimizing local specialization.

Introduction Pharmaceutical treatment in the neonatal intensive care unit (NICU) is challenging, and newborns are often exposed to numerous different medicines during their hospitalization There is currently insufficient knowledge of gestational age dependent medicine disposition, and accordingly the use of off-label medicines, i.e., use of medicines outside its approved marketing authorization, is high. This study aims to estimate the off-label medicine use in Danish neonatal departments. Methods By using data from the Danish National Pharmaceutical Hospital Purchase Database, we identified the most commonly occurring medicines and calculated the on/off-label ratios for premature and term neonates. Data was extracted on ATC level 5 and based on defined daily doses as per WHO. Results Data included was covering the 4 high-level NICUs and 10 of 13 of the intermediate/standard level neonatal departments in Denmark. Of the identified medicines, 87% and 70% did not have approved marketing authorization for use in premature and full-term neonates, respectively. Furthermore one-fifth of the top 100 medicines did not have a (Danish) marketing license. Overall, the presence of off-label medicines was widespread covering virtually all ATC groups and no ATC group had an off-label level lower than 50%. Finally, in 21% of the identified medicines, additives from 8 different chemical groups with potential deleterious effects for neonates were identified. Conclusion Off-label medication in the Danish neonatal departments is widespread, and the current state of neonatal official regulatory drug approval leaves both patients and neonatologists in a limbo between legal pharmaco-regulation and clinical need for pharmacotherapy in neonatology.

In this article, we have use Fuzzy Laplace-Adomian Decomposition method to evaluate the approximate solution of non linear and linear Time Fractional Klein-Gordan equations with suitable initial conditions in Fuzzy environment. We apply Fuzzy Laplace Transform and iterative method under caputo fractional derivative

Let $\Omega$ be a bounded domain in $\mathbb{R}^N, N\geq 2,$ with smooth boundary $\Sigma$ and let $\Omega_1$ be a subdomain of $\Omega$ with smooth boundary $\Gamma,$ such that $\overline{\Omega}_1\subset \Omega$. Denote $\Omega_2 = \Omega \setminus \overline{\Omega}_1.$ Consider the transmission eigenvalue problem \begin{equation*} \left\{\begin{array}{l} -\Delta_p u_1+\gamma_1(x)\mid u_1\mid ^{r-2}u_1=\lambda \mid u_1\mid ^{p-2}u_1\ \ \mbox{in} ~ \Omega_1,\\[1mm] -\Delta_q u_2+\gamma_2(x)\mid u_2\mid ^{s-2}u_2=\lambda \mid u_2\mid ^{q-2}u_2\ \ \mbox{in} ~ \Omega_2,\\[1mm] u_1=u_2,~~\frac{\partial u_1}{\partial\nu_{p}}=\frac{\partial u_2}{\partial\nu_{q}} ~~ \mbox{on} ~ \Gamma,\\[1mm] \frac{\partial u_2}{\partial\nu_{q}}+\beta (x) \mid u_2\mid^{\zeta-2} u_2=0 ~~ \mbox{on} ~ \Sigma, \end{array}\right. \end{equation*} where $\lambda$ is a real parameter $p, q, r, s, \zeta \in (1, \infty)$ and $\gamma_i\in L^{\infty}(\Omega_i), ~i=1, 2, \beta\in L^{\infty}(\Sigma),$ $\beta\geq 0$ a.e. on $\Sigma.$ Under additional suitable assumptions on $p, q, r, s, \zeta$ we prove the existence of a sequence of eigenvalues $\big(\lambda_n\big)_n, \lambda_n\rightarrow \infty.$ The proof is based on the Lusternik-Schnirelmann theory on $C^1-$ manifolds.

The source term identification of the time-fractional diffusion equation under Robin boundary condition is studied. This problem is ill-posed. Therefore, we apply Landweber iterative regularization method, Fractional Landweber iterative regularization method, TSVD method, combining TSVD method and Fractional Landweber iterative regularization method, respectively. The comparisons of these four methods are given, which can help us select the most effective method. The error estimates between the regularized approximate solutions and the exact solution are given under the a priori and a posteriori regularization parameter choice rules. Finally, numerical examples verify the effectiveness of the methods.

Environmental DNA (eDNA) obtained from ancient samples such as sediments, ice or water are valuable data sources for a wide range of disciplines in past and present biodiversity and biogeography [1-4]. Within the field of ancient metagenomics, the number of published genetic datasets has risen dramatically in recent years and have become an increasingly powerful tool to investigate wide-ranging topics [5]. However, the ancient environmental metagenomics remains many issues that should be to be addressed relating to ancient DNA (aDNA) such as degraded nature, incomplete reference databases, sensitivity to contamination by modern DNA [6-8]. This review aims to provide an overview of the use of ancient metagenomics in large-scale ecological and evolutionary studies of individual taxa and communities of both microbes and eukaryotes and illustrate the limitations, risks, and potentiality of this ancient eDNA research via high-throughput sequencing (HTS) technologies. Further, paleogenetic and paleogenomics will provide diverse insights into studying evolution and how the present world came to be.

The spread of the Corona pandemic has led to the emergence of many challenges and needs, including the need to provide educational services electronically. The students with special needs are considered a sensitive group to any changes in the educational process, this study aimed to evaluate the effectiveness of e-learning among students with special hearing needs during the Corona pandemic from the point of view of their parents in Aqaba Governorate, south of Jordan. The researcher analyzed the responses of (35) families of students with special hearing needs to the questionnaire prepared in advance to achieve the goal of this study. The results concluded that there is an average level of effectiveness of e-learning among students with special needs from the point of view of their parents, and that there is a strong statistical relationship for the level of effectiveness according to the age variable of students with special needs from the point of view of their parents.

Deep Neural Networks have been used in a wide variety of applications with significant success. However, their highly complex nature owing to comprising millions of parameters has lead to problems during deployment in pipelines with low latency requirements. As a result, it is more desirable to obtain lightweight neural networks which have the same performance during inference time. In this work, we propose a weight based pruning approach in which the weights are pruned gradually based on their momentum of the previous iterations. Each layer of the neural network is assigned an importance value based on their relative sparsity, followed by the magnitude of the weight in the previous iterations. We evaluate our approach on networks such as AlexNet, VGG16 and ResNet50 with image classification datasets such as CIFAR-10 and CIFAR-100. We found that the results outperformed the previous approaches with respect to accuracy and compression ratio. Our method is able to obtain a compression of 15× for the same degradation in accuracy on both the datasets.

A document by Shmmon Ahmad. Click on the document to view its contents.

 In this short work we will study the simple and absolutely accurate expression for the fine-structure constant with the madelung constant b2(2). This simple expression for the fine-structure constant in terms of the Archimedes constant π is. Also we will present the continued fraction for the fine-structure constant.

A pregnant woman with severe aplastic anemia was managed using biweekly red blood cell transfusion and oral eltrombopag olamine administration during pregnancy. She was diagnosed with severe preeclampsia at 35 weeks of gestation. The severity of aplastic anemia is very important for predicting the course of pregnancy.

Competition in pedagogy is increasing day by day with addition of new teaching domains. English as Foreign Language (EFL) is a new paradigm of teaching that is invading teaching space overall the world. With feel the need of English as an international language, all countries are intended to include EFL courses to coap the need of English language learning and teaching. In this article we will present a narrative overview of EFL with context to university level teaching. Introduction:

Competition in pedagogy is increasing day by day with addition of new teaching domains. English as Foreign Language (EFL) is a new paradigm of teaching that is invading teaching space overall the world. With feel the need of English as an international language, all countries are intended to include EFL courses to coap the need of English language learning and teaching. In this article we will present a narrative overview of EFL with context to university level teaching. Introduction:

IntroductionA notion of life being originated from polymerization of RNA nucleotides seems to be corroborated by circumstantial evidence and some experimental results, however, how it was actually proceeded is not well understood. There are ongoing efforts to synthesize RNA nucleotides in modern labs starting from simple molecular components presumably existed on prebiotic Earth [1-4]. It appears that entire processes leading to formation of the subunits of RNA nucleotides, i.e., ribose sugar, phosphate and nucleobases (adenine (A for short), uracil (U), guanine (G) and cytosine (C)) could be naturally proceeded in prebiotic Earth environment following thermodynamic principles. Alternatively, some intermediate products might be originated from outer space and delivered to Earth. Evidence provided by meteorites suggests this possibility [5]. On the other hand, according to experiments performed in modern labs, the final process, the formation of the RNA nucleotides by joining the subunits is found to be thermodynamically difficult because the subunits must be joined together with covalent bonding that requires to overcome a high activation energy. Thus, there had to be a process that modified the activation energy and promoted the formation of the nucleotides to produce enough quantity for the subsequent polymerization.Once the concentration of RNA nucleotides had reached a certain level, the polymerization took place, and a single strand of RNA polymer was formed on prebiotic Earth. An experiment a simulated prebiotic condition shows that the polymer can grow up to 40 nucleotide units. The max length is determined by stability of the polymer that is constantly subjected to dissociation (bond breaking). The length is well short comparing the length of known short functional RNAs (70~100 units). The dissociation rate linearly increases as the polymer grows in length. In order to grow further, a mechanism that produced longer polymers had to be operated in prebiotic Earth.Autocatalytic reaction is a special property of certain molecules, by which the molecules are multiplied exponentially instead of linearly. Self-replication of RNA enzyme without help of biotic catalysts is known [6]. Also, the self-replication of synthetic molecule has been demonstrated [7]. The molecule is an amino adenosine triacid ester (AATE), which copies itself by attracting another ester molecule to its adenosine end, and an amino adenosine molecule to its ester end. These two molecules then react to form another AATE. The copying process works because of a weak bonding, known as hydrogen bonding which can be broken even by thermal vibration. Hydrogen bonding plays the same role in the self-replication of DNA.It is conceivable that self-replication with a help of non-biotic catalysts might play an essential role for the formation of RNA nucleotides and the polymerization of the nucleotides on prebiotic Earth [8]. Catalysts are widely used to increase yields in modern chemical syntheses. We speculate that non-biotic catalysts played an essential role in the formation of the nucleotides and the polymerization on prebiotic Earth. Metals and clay minerals are known to be good catalysts and certainly existed on prebiotic Earth [9, 10]. Their roles in the process were twofold. First, they provided surfaces on which the subunits were selectively adsorbed. This reaction consequently increased the concentration of the subunits on the surface and allowed the subunits to react each other more frequently. Secondly, they strained and aligned the subunits and nucleotides in proper orientations so that particular reactions became easier due to reduction of the activation energy.

Supplementary Materials: Figures S1, S2, S3, Equation S1

This Supporting Information includes: the detailed dimensions of the MRE valves, the dimensions of the four different MRE geometries investigated, and the detailed setup and parameters of the PID controllers used. Corresponding author Email:  sihan.wang@eng.ox.ac.uk 

A document by Mayer Brezis. Click on the document to view its contents.

Multiparametric magnetic resonance imaging (mpMRI) has emerged as a valuable diagnostic tool in prostate lesion assessment, for which many reports conclude the advantageous use of convolutional neural networks (CNNs) in prostate lesion detection and classification (PLDC). However, the network training inevitably involves prostate magnetic resonance (MR) images from multiple sites/cohorts. There always exists variation in scanning protocol among the cohorts, inducing significant changes in data distribution between source and target domains. This challenge has greatly limited clinical adoption on a large scale. Recent domain adaptation (DA) models can alleviate the inherent cross-site heterogeneity. Some could leverage cross-domain knowledge transfer using whole-slide images, without prior knowledge of lesion regions. In this paper, we propose a coarse mask-guided deep domain adaptation network (CMD²A-Net) in order to develop a fully automated framework for PLDC using multi-cohort images. No category or mask label is required from the target domain. A coarse segmentation module is trained to cover the possible lesion-related regions, so that attention maps can be generated to dedicate the local feature extraction of lesions within those regions. As a result, the features of both prostate lesion and region can be fused to align the robust features between the source and target domains. Experiments have been performed on 512 mpMRI sets from datasets of PROSTATEx (with 330 sets) and two cohorts, A (with 74 sets) and B (with 108 sets). Using the ensemble learning, our CMD²A-Net accomplishes an AUC of 0.921 in cohort A and 0.913 in cohort B, demonstrating its transferability from a large-scale public dataset PROSTATEx to our small-scale target domains. Our results and ablation study also support the CMD²A-Net’s effectiveness in lesion classification between benign or malignant, compared to the state-of-the-art models Corresponding author(s) Email:   kwokkw@hku.hk (K.W. Kwok), varv@hku.hk (V. Vardhanabhuti)

Mark Davidson Jewell1 and Graham Bell1,21Department of Biology, McGill University; 1205 ave Docteur Penfield, Montreal, Quebec H3A 1B1, Canada.2Redpath Museum, McGill University; 859 Sherbrooke St West, Montreal, Quebec H3A 0C4, Canada.

Nitric oxide (NO) is a ubiquitous signaling molecule in a variety of physiological and pathological process in living organisms. A two-photon probe, i.e., 2-acetyl-6-dialkylaminonaphthalene as the reporter and an o-diaminobenzene as the reaction site for NO, linked by prolinamide (ANO1), has been synthesized. Based on the experimental study, five other two-photon probes have been designed by substituting the naphthalene fluorophore in ANO1 with the luciferin analogue (ANO2), pyrene (substitution at 1,6-position, ANO3, and 2,7-position, ANO3’), fluorene (ANO4), and boron-dipyrromethene (ANO5) units. DFT/TDDFT studies have been conducted on both experimental two-photon probe ANO1 and designed ANOn (n=2–5). Our results indicated that for designed probes, both absorption and emission spectra show red shifts compared with ANO1. The one- and two-photon absorption band positions as well as the emission wavelength do have no significant change for each probe before and after reaction with NO. However, the fluorescence intensities are enhanced after reaction with NO. ANO3 and ANO4 have large two-photon absorption cross sections. Furthermore, analysis of molecular orbitals is exhibited to interpret the photoinduced electron transfer mechanism between the donor and acceptor.

Due to their special geographical locations and environments, plateau lakes play a key role in maintaining regional water balance, but lake water storage changes are upsetting this balance. Based on data from lakes on the Tibetan Plateau (TP), this study used the Spatial Processes in Hydrology (SPHY) model to simulate the runoff process in the Siling Co basin from 2000-2016 and estimated the changes in water storage of Siling Co and the contribution of each component of runoff into the lake. The results showed that the water storage capacity of Siling Co has increased by 1.157 billion m 3/yr, declines in precipitation have significantly reduced baseflow(BF), rainfall runoff(RR), and Snow runoff(SR), while temperature increases have raised glacier runoff(GR). The simulated average runoff showed that BF, GF, RR, and SR contribute 24%, 22%, 16%, and 38%, respectively, of the flow into Siling Co. Based on hypothetical climate change scenarios and two Shared Socioeconomic Pathways (SSP1-2.6 and SSP3-7.0) from the MRI-ESM2-0 GCMs, this study estimated that a 10% increase in precipitation could lead to a 28.45% increase in total runoff, while a 1 °C increase in temperature could lead to a 9.49% decrease in runoff. The average runoff depth of the basin is expected to increase by 29.77-39.13 mm, since the temperature and precipitation may increase significantly from 2020-2050. The intensification of glacial melting caused by the increase in temperature continues, posing a greater challenge to many water resources management problems caused by the expansion of lakes.

Rosuvastatin is a lipid-lowering medication that is routinely used to reduce blood cholesterol levels. It acts by inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol production, preventing de novo cholesterol synthesis and increasing the amount of low-density lipoprotein (LDL) receptors on the liver surface, resulting in lower blood LDL levels. Rosuvastatin has some adverse effects, including moderate ones like headache, stomach discomfort, nausea, and weakness, as well as major ones like muscle, liver, and renal issues including severe muscular pain, decreased appetite, dark-colored urine, and continuous nausea/vomiting. According to recent research, rosuvastatin medication can produce renal tubular toxicity in persons who have no prior history of kidney disease. Rosuvastatin has been linked to myalgia, rhabdomyolysis, and elevated creatine phosphokinase levels. If patients on rosuvastatin have muscular or renal difficulties, they should seek emergency medical assistance. Nonetheless, Rosuvastatin’s lipid-lowering effects exceed the danger of adverse effects. Strong adherence to these safety precautions can enhance Rosuvastatin’s safety profile and allow it to be given safely for hypercholesterolemia.