In this work, we present basic results and applications of Stepanov pseudo almost periodic functions with measure. Using only the continuity assumption, we prove a new composition result of $\mu$-pseudo almost periodic functions in Stepanov sense. Moreover, we present different applications to semilinear differential equations and inclusions in Banach spaces with weak regular forcing terms. We prove the existence and uniqueness of $\mu$-pseudo almost periodic solutions (in the strong sense) to a class of semilinear fractional inclusions and semilinear evolution equations, respectively, provided that the nonlinear forcing terms are only Stepanov $ \mu $-pseudo almost periodic in the first variable and not a uniformly strict contraction with respect to the second argument. Some examples illustrating our theoretical results are also presented.

Childhood rashes or exanthemas are common and are usually relatively benign. There are many causes of rash in children, including mainly viruses, and less often bacterial toxins, drugs, allergens, and other diseases. Viral exanthema often appears while children are taking a medication in the course of a viral infection; it can mimic drug exanthema, and is perceived as a drug allergy in 10% of cases. The drugs most commonly implicated are beta-lactams (BL) and nonsteroidal anti-inflammatory drugs (NSAIDs). Viruses, commonly Epstein Barr virus (EBV), human herpesvirus 6 (HHV6) and cytomegalovirus (CMV), and the bacterium Mycoplasma pneumoniae, may cause exanthema either from the infection itself (active or latent) or because of interaction with drugs that are taken simultaneously. Determination of the exact diagnosis requires a careful clinical history and thorough physical examination. Haematological and biochemical investigations and histology are not always helpful in differentiating between the two types of exanthema. Serology or polymerase chain reaction (PCR) can be helpful, although a concomitant acute infection does not exclude drug hypersensitivity. A drug provocation test (DPT), although considered the gold standard for the diagnosis, is not preferred by the patients. Skin tests are not well tolerated, and in vitro tests, such as the basophil activation test and lymphocyte transformation, are of low sensitivity and specificity and their relevance is debatable. Based on current evidence, we propose a systematic clinical approach for timely differential diagnosis and management of rashes in children who present a cutaneous eruption while receiving a drug.

Partial clonality is widespread across the tree of life, but most population genetics models are designed for exclusively clonal or sexual organisms. This gap hampers our understanding of the influence of clonality on evolutionary trajectories and the interpretation of population genetics data. We performed forward simulations of diploid populations at increasing rates of clonality (c), analysed their relationships with genotypic (clonal richness, R, and distribution of clonal sizes, Pareto β) and genetic (FIS and linkage disequilibrium) indices, and tested predictions of c from population genetics data through supervised machine learning. Two complementary behaviours emerged from the probability distributions of genotypic and genetic indices with increasing c. While the impact of c on R and Pareto β was easily described by simple mathematical equations, its effects on genetic indices were noticeable only at the highest levels (c>0.95). Consequently, genotypic indices allowed reliable estimates of c, while genetic descriptors led to poorer performances when c<0.95. These results provide clear baseline expectations for genotypic and genetic diversity and dynamics under partial clonality. Worryingly, however, the use of realistic sample sizes to acquire empirical data systematically led to gross underestimates (often of one to two orders of magnitude) of c, suggesting that many interpretations hitherto proposed in the literature, mostly based on genotypic richness, should be reappraised. We propose future avenues to derive realistic confidence intervals for c and show that, although still approximate, a supervised learning method would greatly improve the estimation of c from population genetics data.

Background: Arteriovenous access (AV) thrombosis is important and preventable problem among chronic hemodialysis (HD) patients. On the other hand, systolic blood pressure (SBP) alteration relates with higher cardiovascular mortality among these patients. In this study, we investigated the relation between SBP changes and arteriovenous access (AV) thrombosis. Methods: 50 HD patients with thrombosis and 50 HD patients without thrombosis were included in the study. Odds ratios and 95% confidence intervals were estimated with multivariate adjusted logistic regression models to determine the association between potential thrombosis-related risk factors and thrombosis risk. Results: Elder adults, women, and patients with arteriovenous grafts, lower intradialytic SBP and higher SBP variations during dialysis sessions had higher incidence of AV access thrombosis. Chronic inflammation and mineral metabolism related parameters were also found to be abnormal at the time of AV access thrombosis. Conclusions: Close monitoring and management of intra-dialytic hypotension, SBP variation in every dialysis session and correction of biochemical parameters are critical for earlier identification and prevention of AV access thrombosis in HD patients.

Background: Mutations in the filaggrin gene (FLG) affect epidermal barrier function and increase the risk of atopic dermatitis (AD). We hypothesized that FLG mutations affect immune cell composition in a general pediatric population. Therefore, we investigated if school-aged children with and without FLG mutations have differences in immune cell numbers. Methods: This study was embedded in a population-based prospective cohort study, the Generation R Study, and included 523 children of European genetic ancestry aged 10 years. The most common FLG mutations in the European population (R501X, S1085CfsX36, R2447X and S3247X) were genotyped. Additionally, 11-color flow cytometry was performed on peripheral blood samples to determine helper T (Th), regulatory T (Treg) and CD27+ and CD27- memory B cells. Sensitivity analysis was performed in 102 AD cases, assessed by parental questionnaires. Results: FLG mutations were observed in 8.4% of the total population and in 15.7% of the AD cases. Children with any FLG mutation had higher Th22 cell numbers compared to FLG wild-type children. Children with and without FLG mutations had no difference in Th1, Th2, Th17, Treg or memory B cell numbers. Furthermore, in children with AD, FLG mutation carriership was not associated with differences in T- and B-cells or their subsets. Conclusions: School-aged children with FLG mutations have higher Th22 cell, which might suggest an immunological defense mechanism to an altered skin barrier function. No associations between Th or Treg cells and FLG mutations suggests that FLG mutations do not otherwise affect immune composition in a general pediatric population.

Mounting evidence suggests that rapid evolutionary adaptation may rescue some organisms from the impacts of ongoing climate change. However, evolutionary constraints might hinder this process, especially when different aspects of environmental change generate antagonistic selection on genetically correlated traits. Here, we use individual-based simulations to explore how genetic correlations underlying the thermal physiology of ectotherms might influence their responses to the two major concomitant components of climate change---increases in mean temperature and thermal variability. We found that genetic correlations can influence population dynamics under climate change, with declines in population size varying three-fold depending on the type of correlation present. Surprisingly, populations whose thermal performance curves were constrained by genetic correlations often declined less rapidly than unconstrained populations. Our results suggest that accurate forecasts of the impact of climate change on ectotherms will require an understanding of the genetic architecture of the traits under selection.

Tuberculosis (TB) and its emerged drug resistance exert huge threats on the global health, therefore development of novel anti-TB antibiotics is very essential. Ilamycin-E1/E2 is a pair of cycloheptapeptide enantiomers obtained from a marine-derived Streptomyces atratus SCSIO ZH16-ΔilaR mutant, and become promising anti-TB lead compounds due to their significant anti-TB activities, but their low titer hampered the further clinical development. In this work, the statistical Plackett-Burman design (PBD) model was applied to screen out bacterial peptone as the only significant but negative factor affecting the ilamycin-E1/E2 production. Subsequent single factor optimization revealed that replacement of bacterial peptone with malt extract eliminated the accumulation of porphyrin-type competitive byproduct, and the titer of ilamycin-E1/E2 in shaking flasks was improved from original 13.6±0.8 to 142.7±5.7 mg/L for about 10.5 folds. Furthermore, a pH coordinated feeding strategy was first adopted in scaled-up production of ilamycin-E1/E2. The obtained titer of ilamycin-E1/E2 in 30L was 169.8±2.5 mg/L, while in 300L fermentor was only 131.5±7.5 mg/L due to the unsynchronization of feeding response and pH change. Therefore, the continuous pulse feeding strategy was further applied in 300L fermentor and finally achieved 415.7±29.2 mg/L ilamycin-E1/E2, which represented about 30.5 folds improvement at last. Our work provided the solid basis to achieve sufficient ilamycin-E1/E2 lead compounds and support their potential anti-TB drug development.

Anomalous aortic origin of a coronary artery from the opposite sinus is a rare congenital condition that can cause sudden death in young people. When it is associated with acute aortic dissection, acute myocardial infarction can occur due to enlargement of the sinus of Valsalva. We report the case of a 71-year-old man with anomalous origin of the right coronary artery from the left sinus of Valsalva, who developed right ventricular infarction due to the compression of the right coronary artery between the aorta and pulmonary artery trunk.

A giant coronary artery aneurysm (GCAA) concurrent with coronary artery fistula is a rare condition, and it becomes even more unusual when combined with a single coronary artery (SCA) anomaly. Here we report such an extremely rare case, who is a 35-year-old woman presenting with severe chest distress. A GCAA with fistula to the right ventricle was noted, occurring in a single coronary artery, diagnosed by multimodality cardiovascular imaging techniques. Both GCAA and coronary artery fistula can cause severe cardiac complications, which jeopardize life. While an SCA is mostly asymptomatic, it may also lead to sudden cardiac death as well. Therefore, surgical intervention was recommended. We chose a novel thrombus-inducing strategy to eliminate the GCAA and repair the fistula. Symptoms were relieved after the surgery, and the patient remained asymptomatic over 8 months of follow-up.

Runs of long homozygous stretches (ROH) are considered to be the result of consanguinity and usually contain recessive deleterious disease causing mutations (Szpiech et al., 2013). Several algorithms have been developed to detect ROHs. Here, we developed a simple, alternative strategy by examining X chromosome non-pseudoautosomal region to detect the ROHs from next generation sequencing data utilizing the genotype probabilities and the Hidden Markov Model algorithm as a tool, namely ROHMM. It is implemented purely in java and contains both command-line and a graphical user interface. We tested ROHMM on simulated data as well as real population data from 1000G Project and a clinical sample. Our results have shown that ROHMM can perform robustly producing highly accurate homozygosity estimations under all conditions thereby meeting and even exceeding the performance of its natural competitors.

A PRIMARILY CLINICIAN’S RESPONSIBILITY

The patient was a 64-year-old woman, who stabbed her neck with a kitchen knife in an attempt to commit suicide. The tip of the knife was chipped and lodged into the first thoracic vertebra. It was removed using a drill.

Helminths are an important cause of parasite infestation in low-resource countries. The Majority spread with soil to skin contact. In unusual patients presenting below 1 year, treatment can be challenging. The disease can be self-limiting, treatment reduces progression to serious disease. Here, we present a three-month-old with Cutaneous Larva Migrans.

Background: Cardiac resynchronisation therapy-defibrillator (CRT-D) implantation via the cephalic vein is feasible and safe. Recent evidence has suggested a higher implantable cardioverter defibrillator (ICD) lead failure in multi-lead defibrillator therapy via the cephalic route. We evaluated the relationship between CRT-D implantation via the cephalic and ICD lead failure. Methods: Data was collected from three CRT-D implanting centres between October 2008 – September 2017. In total 631 patients were included. Patient and lead characteristics with ICD lead failure were recorded. Comparison of ‘cephalic’ (ICD lead via cephalic) vs ‘non-cephalic’ (ICD lead via non-cephalic route) cohorts was performed. Kaplan-Meier survival and a Cox-regression analysis were applied to assess variables associated with lead failure. Results: The cephalic and non-cephalic cohorts were equally male (82.2% vs 78.3%, p=0.28), similar in age (69.7±11.5 vs 68.7 ± 11.9, p=0.33) and body mass index (BMI) (27.7±5.1 vs 27.1±5.7, p=0.33). Most ICD leads were implanted via the cephalic vein (73.7%) and patients had a median of 2.8 leads implanted via this route. The rate of ICD lead failure was low and similar between both groups (0.4%/year vs 0.14%/year, p=0.34). Female gender was more common in the lead failure cohort than non-failure (50% vs 18.2%, respectively, p=0.01) as was hypertension (90% vs 54%, respectively, p=0.03). On multivariate Cox regression, female sex (p=0.007), hypertension (p=0.041) and BMI (p=0.042) were significantly associated with ICD lead failure. Conclusion: CRT-D implantation via the cephalic route is not associated with premature ICD lead failure. Female gender, BMI and hypertension correlate with lead failure.

Working memory (WM) impairment has been well characterized in normal ageing. Various studies have explored changes in either the regional activity or the interregional connectivity underlying the WM ageing process. We proposed that brain activity and connectivity would independently alter with ageing and affect WM performance. WM was assessed with a classical N-back task during functional magnetic resonance imaging in a community-based sample comprising 168 elderly subjects (aged 55 to 86 years old). Following the rationale of background functional connectivity, we assessed age-related alterations in brain activity and seed-based interregional connectivity independently. Analyses revealed age-related decrease in the activity of the inferior parietal lobule (IPL) and an increase in the activity of the ventral anterior cingulate cortex (ACC), and the local functional dysfunctions were accompanied by alterations in their connectivity to other cortical regions. Importantly, regional activity impairments in the IPL and ACC could mediate age-related effects on accuracy rate and reaction time, respectively, and those effects were further counterbalanced by enhancement of their background functional connectivity. We thus claimed that age-induced alterations in regional activity and interregional connectivity occurred independently and contributed to WM changes in ageing. Our findings presented the way brain activity and functional connectivity interact in the late adulthood, thus providing a new perspective for understanding WM and cognitive ageing.

In this paper, we investigate pattern dynamics in a reaction-diffusion-chemotaxis food chain model with predator-taxis, which enriches previous studies about diffusive food chain models. By virtue of diffusion semigroup theory, we first show the global classical solvability and uniform boundedness of the considered model over a bounded domain Ω ⊂ R N ( N ≥ 1 ) with smooth boundary. Then the linear stability analysis for the considered model shows that chemotaxis can induce the unique positive spatially homogeneous steady state loses its stability via Turing bifurcation and Turing-spatiotemporal Hopf bifurcation, which results in the formation of two kinds of important spatiotemporal patterns: stationary Turing pattern and oscillatory pattern. Simultaneously, the threshold values for Turing bifurcation and Turing-spatiotemporal Hopf bifurcation are given explicitly. In addition, the existence and stability of non-constant positive steady state that bifurcates from the positive constant steady state is investigated by the abstract bifurcation theory of Crandall-Rabinowitz and eigenvalue perturbation theory. Finally, numerical simulations are performed to verify our theoretical results, and some interesting non-Turing pattern are found in temporal Hopf parameter space by numerical simulation.

Lipofibromatous hamartoma is an uncommon tumor that causes nerve enlargement due to fatty adipose tissue infiltration in peripheral nerves being the median nerve at the carpal tunnel the most commonly affected site, typically associated with macrodactyly. Here we present a case which affected a digital branch of the median nerve

In the present paper, we study the stochastically-induced behavior of a non-linear volcanic model containing three prognostic variables: the plug velocity $u$, the pressure under the plug, and the conduit volume $V$. The nouvelle phenomena of noise-induced transitions from the equilibrium to the cycle in the bistability parametric zone and noise-induced excitement with the generation of spike oscillations in the monostability zone are found in the presence of N-shaped friction force. To study these phenomena numerically, we used the computations of random solutions, the phase trajectories and time series, the statistics of interspike intervals, and the mean square variations. To study these phenomena analytically, we applied the stochastic sensitivity function technique and the confidence domains method. This approach is used to predict the noise-induced transition from a “dormant volcano” state to the “active volcano” mode. From the physical point of view, the volcano is capable to become active under the influence of external noises in the friction force, which model various compositions and properties of volcanic rocks. What is more, the volcanic plug can pop out when it is slipping heavily, and the volcano can erupt.