Drop breakup experiments were carried out in a stirred tank using the high-speed online camera. Breakup behaviors of drop breakup time, multiple breakage, and breakup rate were investigated. Experimental results show that the drop breakup time is mainly controlled by the interfacial tension and drop diameter, while is almost independent of the rotating speed. Besides, the dispersed phase viscosity has a slight influence on the breakup time. An empirical correlation for the breakup time is proposed and is further verified by comparing with the results of Solsvik and Jakobsen (Chem. Eng. Sci., 2015, 131: 219-234). The percentage of multiple breakage comparing to binary breakup was statistically counted. The results indicated that the dimensionless drop diameter η = d / dmax can be adopted to characterize the proportion of binary breakup. Finally, the breakup rate was experimentally measured and the breakup probability was calculated using the inverse method.

Aims: To evaluate the effect of the combination of carotegrast methyl with rifampicin, a potent inhibitor of organic anion transporter polypeptide, on the pharmacokinetics (PK), safety and tolerability. Methods: In this 2 x 2 crossover study in 20 healthy Japanese adults, 10 subjects received carotegrast methyl 960 mg and rifampicin 600 mg on day 1, and received carotegrast methyl 960 mg on day 8. The subjects in the other sequence received the same treatments but in the opposite order. When the 90% confidence interval (CI) of the geometric mean ratio of the AUC0-t and Cmax for carotegrast, the main active metabolite of carotegrast methyl, with/without rifampicin fell within the range of 0.80 – 1.25, it was deemed that no PK interaction occurred. Adverse events (AEs) were monitored. Results: The Cmax and AUC0-t for carotegrast with/without rifampicin was 11724.5 ± 6097.6 vs 2620.1 ± 1843.0 ng mL-1, and 55046.0 ± 23427.8 vs 9849.9 ± 4580.6 ng h mL-1, respectively. The ratios (90% CI) of the Cmax and AUC0-t with/without rifampicin were 4.78 (3.64 – 6.29) and 5.59 (4.60 – 6.79), respectively, indicating carotegrast has a PK interaction with rifampicin. The combination with rifampicin also increased the exposure of carotegrast and its metabolites. The incidence of any AEs with/without rifampicin was five (25.0%) and one (5.0%), respectively. Conclusion: Coadministration of carotegrast methyl with rifampicin significantly increased exposure of carotegrast compared with carotegrast methyl administration alone. However, no increase in the incidence of adverse drug reactions due to coadministration with rifampicin was observed.

Gene function conservation is crucial in molecular ecology, especially for key traits like growth and maturation in teleost fish. The vgll3 and six6 genes are known to influence age-at-maturity in Atlantic salmon, but their impact on other fish species is poorly understood. Here, we investigated the association of vgll3 and six6 in the domestication of gilthead seabream and European seabass, both undergoing selective breeding for growth-related traits in the Mediterranean. We analysed two different sets of samples using two different genotyping approaches. The first dataset comprised farmed and wild populations from Greece, genotyped for SNPs within the genomic range of the two genes (“gene-level genotyping”). The second dataset examined 300k to 600k SNPs located in the chromosomes of the two genes, derived from a meta-analysis of a Pool-Seq experiment involving farmed and wild populations distributed widely across the Mediterranean (“chromosome-level genotyping”). The gene-level analysis revealed a significant effect of domestication on both genes in each species. This finding was partially supported by the chromosome-level analysis, identifying highly differentiated regions associated with domestication at varying distances from the candidate genes. Noteworthy genomic features were found, such as a CpG island in gilthead seabream and novel candidate genes in European seabream, warranting further investigation. These findings support a putative role of vgll3 and six6 in the maturation and growth of gilthead seabream and European seabass, emphasizing the need for further research on their conserved function.

Vitamin D-dependent rickets type 1 (VDDRIA) is an autosomal recessive disease caused by mutations in the Cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1) gene encoding the enzyme 1 alpha-hydroxylase. We report a known VDDRIA case presenting with hypotonia, growth and developmental disorders.

Aim: Alemtuzumab is a lymphodepleting monoclonal antibody utilized in conditioning regimens for allogeneic hematopoietic cell transplantation (HCT). A therapeutic range of 0.15-0.6 µg/mL on the day of transplantation is associated with better HCT outcomes. The purpose of this study was to characterize alemtuzumab population pharmacokinetic/pharmacodynamic (PK/PD) and to propose individualized subcutaneous dosing schemes to achieve this optimal level for pediatric patients. Methods: Alemtuzumab concentration and absolute lymphocyte count (ALC) profiles were obtained from 29 patients with non-malignant disorders undergoing HCT. PK/ PD analyses were performed using non-linear mixed effects modeling. Monte Carlo simulation was conducted to evaluate different improved dosing approaches. Results: A one-compartment model with sequential zero- and first-order absorption adequately described subcutaneously administered alemtuzumab PK. Model fit was significantly improved by including allometrically scaled body weight on clearance (0.080 L/h/70kg) and volume of distribution (17.4 L/70kg). ALC reduction following subcutaneous alemtuzumab was swift. An inhibitory Emax model best characterized the relationship between alemtuzumab concentration and ALC. Emax and EC50 were estimated as 1.18*103/µL and 0.045µg/mL, respectively. The currently used per kg dosing was found to cause uneven alemtuzumab exposure across different age and weight cohorts. Simulations indicated target achieving dose as allometry-based of 18 mg*(weight/70)0.75 or body surface area (BSA)-based of 10 mg/m2, divided over 3 days, with a potential individualized top-up dose; both of which yielded similar results. Conclusion: An allometry- or BSA-based starting dosing regimen in combination with individualized Bayesian PK estimation using concentration feedback is proposed for alemtuzumab precision dosing in children undergoing allogeneic HCT.

Background: Remote ischemic preconditioning (rIPC) has been applied to attenuate tissue injury. We tested the hypothesis that rIPC applied to fetal lambs undergoing cardiac bypass (CB) reduces fetal systemic inflammation and placental dysfunction. Methods: Eighteen fetal lambs were divided into 3 groups: sham, CB control, and CB rIPC. CB rIPC fetuses had a hindlimb tourniquet applied to occlude blood flow for 4 cycles of a 5-minute period, followed by a 2-minute reperfusion period. Both study groups underwent 30 minutes of normothermic CB. Fetal inflammatory markers, gas exchange, and placental and fetal lung morphological changes were assessed. Results: The CB rIPC group achieved higher bypass flow rates (p<.001). After CB start, both study groups developed significant decreases in PaO2, mixed acidosis and increased lactate levels (p<.0004). No significant differences on tissular edema were observed on fetal lungs and placenta (p>.391). Expression of toll-like receptor-4 and ICAM-1 in the placenta and fetal lungs did not differ among the 3 groups, as well as with VCAM-1 of fetal lungs (p>.225). Placental VCAM-1 expression was lower in the rIPC group (p<.05). Fetal interleukin-1 (IL-1) and thromboxane A2 (TXA2) levels were lower at 60 minutes post-CB in the CB rIPC group (p<.05). There was no significant differences in TNF-α, PGE2, IL-6 and IL-10 plasma levels of the three groups at 60-minute post-bypass (p>.133). Conclusion: Although rIPC allowed for increased blood flow during fetal CB and decreased in IL-1 and TXA2 levels and placental VCAM-1, it did not prevent placental dysfunction in fetal lambs undergoing CB.

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We calculate the concerted pathway of 1, 2-bromochloroethane monocation to C2H4+ and BrCl using the Minnesota density functional M06-2X and the def2-TZVP basis set. We also calculate the elimination channel of 1, 2-bromochloroethane monocation to C2H4 and BrCl+ for the reason that positive charge can be assigned to either moiety in the fragmentation process of 1,2-C2H4BrCl+. Our results demonstrate that the elimination channel of 1, 2-bromochloroethane monocation to C2H4+ and BrCl is preferred, and the singly charged 1,2-bromochloroethane ions surpass two energy barriers and then separate into C2H4+ + BrCl by an asynchronous concerted process. Experimentally, we confirm that this elimination channel is from the dissociative ionization process of 1,2-bromochloroethane monocation by dc-slice imaging technique. Besides, we can see in laser-induced time-of-flight mass spectra of 1,2-bromochloroethane that fragment ion C2H4+ occur at the laser intensity of 6.0×1013 W/cm2 while BrCl+ occur at a higher laser intensity, which is consistent with the theoretical results that appearance energy of ion C2H4+ should be lower than that of BrCl+, and this is the reason why the low-velocity component of ion BrCl+ is absent from our sliced images.

Left ventricular free wall rupture (LVFWR) is a most rare but often lethal mechanical complication of acute myocardial infarction (AMI). The mortality rate for LVFWR is described from 75% to 90% and it is the cause for 20% of in-hospital deaths after AMI. Death results essentially from the limited time available for emergent intervention after onset of symptoms. Emergency surgery is indicated and normally the rupture site is easily identified, but it may not be apparent macroscopically, corresponding to transmyocardial or subepicardial dissection with an external rupture far from the infarction site, or already thrombosed and contained. Repair of the ventricular wall is usually achieved either by suturing the edges of the tear or closing it with patches of artificial material or biological tissues, usually using some kind of biological glue. However, several cases of successful conservative management have been described. In this Editorial, I comment on the metanalysis conducted by Matteucci et al, published in this issue of the Journal, including 11 non-randomized studies and enrolling a total of 363 patients, which brings a great deal of new knowledge that can help not only in the prevention but also in the management of this dreadful complication of AMI.

Background: The marked heterogeneity in CF disease complicates selection of those most likely to benefit from existing or emergent treatments. Objective: We aimed to predict progression of bronchiectasis in preschool children with CF. Methods: Using data collected up to three years of age, in the Australian Respiratory Early Surveillance Team for CF (AREST CF) cohort study, clinical information, chest computed tomography (CT) scores and biomarkers from bronchoalveolar lavage were assessed in a multivariable linear regression model as predictors for CT bronchiectasis at age 5-6. Results: Follow-up at 5-6 years was available in 171 children. Bronchiectasis prevalence at 5-6 was 134/171 (78%) and median bronchiectasis score 3 (range 0-12). The internally validated multivariate model retained eight independent predictors accounting for 37% (Adjusted R2) of the variance in bronchiectasis score. The strongest predictors of future bronchiectasis were: pancreatic insufficiency, repeated intravenous treatment courses, recurrent lower respiratory infections in the first 3 years of life and lower airway inflammation. Dichotomizing the resulting prediction score at a bronchiectasis score of above the median resulted in a diagnostic odds ratio of 13 (95% CI 6.3-27) with a positive and negative predictive values of 80% (95%CI 72%-86%) and 77% (95% CI 69%-83%) respectively. Conclusion: Early assessment of bronchiectasis risk in children with CF is feasible with reasonable precision at a group level, which can assist in high-risk patient selection for interventional trials. The unexplained variability in disease progression at individual patient level remains high, limiting the use of this model as a clinical prediction tool.

Chromosome 4q Deletion Syndrome (4QDS) is a rare chromosomal deletion that presents with various congenital defects that could affect anesthetic management. We present a patient with known 4QDS who underwent successful general anesthetic induction, tracheal intubation, and subsequently, bilateral quadratus lumborum nerve blocks, during laparoscopic inguinal hernia repair surgery.

Stretchable gas barrier films achieved by hydrogen-bond self-assembly of nano-brick multilayers

Nephronophthisis is a pediatric genetic disease. The kidney effect is characterized by a CTN leading to ESRD. Many syndromes could be associated with NPHP. We reported a child affected by NPHP with dextrocardia, LSVC and LAV where the diagnostic was done by fluoroscopy after encountering unusual difficulties to perform CVC.

Multi-level societies are complex social systems where basic core units associate in a hierarchical manner, allowing animals to adjust group size in response to local conditions. Each tier of multi-level societies may have evolved under different selective pressures and understanding the effect of temporal variation in these pressures may help determine why these types of social systems form. Our goal was to examine the degree of temporal variability in inter-unit associations in a multi-level society of Rwenzori Angolan colobus monkey (Colobus angolensis ruwenzorii), and to determine whether social or ecological factors correlated with association patterns. Using social network analyses, we described the association patterns of 12-13 core units over 21-months and investigated the effect of changes in rainfall, food availability, and inter-unit dispersals. We found that core unit networks were denser and more clustered when fruit was abundant, likely due to reduced food competition. Male dispersals also occurred more at these times, suggesting that greater band cohesion allowed males to prospect for dispersal opportunities. Within the band, we observed the formation of an all-male unit and the transfer of one core unit between clans. Our findings highlight how ecological conditions can influence association patterns, interunit relationships, and ultimately social organization.

Introduction- Cannabis use disorders are global emerging problem nowadays, with high prevalence and morbidity. Though cognitive impairments are one of the most replicated findings in individuals with cannabis dependence, but there are very few studies assessed cognitive functioning as a risk factor for cannabis use disorder. In this study, we assessed cognitive functioning as an endophenotype in cannabis use disorders. Methodology- In this study comparison of cognitive functioning was done among three groups- patients with cannabis dependence syndrome, their first degree relative (FDR) and normal healthy controls (HC). Each group included 30 participants. Individuals of all three groups were assessed in domains of complex attention, executive functions, language, learning and memory and perceptual-motor. Results- Performance of patients with cannabis dependence was impaired in attention, verbal memory, executive functions compared to both other groups. Attention, semantic verbal fluency and memory were found to be an endophenotype as both patient and FDR group performed poorly than HC group. Verbal memory was impaired in patients’ group compared to group of first-degree relatives, whose performance in-turn impaired than normal healthy controls. Performances of verbal and visual memory were correlated positively with age of onset and negatively with frequency of cannabis intake. Age of first-degree relatives was inversely correlated with verbal memory. Conclusion- Performance of individuals with cannabis dependence was impaired than normal healthy controls in all domains of cognitive functioning. As per definition, verbal memory could be considered as an endophenotype marker in cannabis use disorders.

The aims of the current review were to identify, in the context of people with acquired communication disorders: factors which influence medication adherence, current interventions targeting medication adherence, and how medication adherence is currently measured. This study was conducted and reported in accordance with both PRISMA and SWiM guidelines. Two authors independently screened the results of a literature search, assessed risk of bias, and extracted relevant data. Eight studies were identified for inclusion. Four of the studies presented information relating to current interventions which target medication adherence for people with acquired communication disorders. Four of the studies investigated factors which influence medication adherence for people with acquired communication disorders. Seven of these eight studies outlined methods used for measuring medication adherence. The results of this review indicate that patient related factors are most associated with medication non-adherence in a population with acquired communication disorders, followed by socio-economic factors and medication-related factors. Despite the recognised importance of medication adherence, no gold standard of assessment or intervention currently exist for this population. Half of the included studies replaced patients with communication difficulties with caregiver proxies, thus reducing opportunities for patients to participate meaningfully in research. The term “acquired communication disorders” encompasses a range of conditions with diverse aetiologies, presentations, and needs, and future research should be tailored to specific patient groups most at risk of medication non-adherence, namely those with aphasia and cognitive-communication impairments. Patients should be empowered to participate in future research to ensure the literature accurately represents their lived experience.

Climate change in terms of regional warming and modifications in precipitation regimes has large impacts on streamflow in regions where both rainfall and snowmelt are important runoff generating processes like in Norway. Hydrological impacts of recent changes in climate are usually investigated by trend analyses applied on annual, seasonal, or monthly time series. However, neither of them can detect sub-seasonal changes and their underlying causes. Based on high-resolution trend analyses (i.e., applying the Mann-Kendall test on 10-day-moving-averaged daily time series), this study investigated sub-seasonal changes in daily streamflow, rainfall, and snowmelt in 61 and 51 catchments in Western vs. Eastern Norway (Vestlandet vs. Østlandet), respectively, over the period 1983-2012. The relative contribution of rainfall vs. snowmelt to daily streamflow and the changes therein have also been estimated to identify the changing relevance of these driving processes over the same period. Detected changes in daily streamflow were finally attributed to changes in the most important hydro-meteorological drivers using multiple-regression models with increasing complexity. Results reveal a coherent picture of earlier spring flow timing in both regions due to earlier snowmelt. Other streamflow trend patterns differ between both regions: Østlandet shows increased summer streamflow in catchments up to ~1100 m a.s.l. and slightly increased winter streamflow in about 50 % of the catchments, while trend patterns in Vestlandet are less coherent. The importance of rainfall for streamflow contribution has increased in both regions, and the trend attribution reveals that changes in rainfall and snowmelt can explain streamflow changes to some degree in periods and regions where they are dominant (snowmelt: spring and Østlandet; rainfall: autumn and Vestlandet). However, detected streamflow changes can be best explained by adding temperature as an additional predictor which indicates the relevance of additional driving processes for streamflow changes like increased glacier melt and evapotranspiration.

Gastric cancer was diagnosed with dilation of the main pancreatic duct. SPACE revealed adenocarcinoma, total gastrectomy with distal pancreatectomy were underwent. More case reports are needed to determine whether adjuvant chemotherapy is indicated for patients with PCIS and whether the extent of lymph node dissection can be safely reduced.