Longitudinal dispersivity is a key parameter for numerical simulation of groundwater quality and this parameter is highly variable in nature. The use of empirical equations and the inverse solution are two main methods of estimating longitudinal dispersivity. In this study, the estimation of values and aquifer-wide spatial distribution of longitudinal dispersivity parameter using a combined approach i.e. a combination of empirical equation method (Pickens and Grisak, Arya, Neuman, and Xu & Eckstein equations), the inverse solution method (using the MT3DMS model with non-automatic calibration) and the aquifer zoning technique is investigated. The combined approach applied to Bandar-e-Gaz aquifer in northern Iran, and Willmott’s index of agreement was used to assess the precision of simulation of total dissolved solids in this aquifer. The values of this criterion were 0.9985 to 0.9999 and 0.9756 to 0.9992 in calibration and validation periods that show the developed combined approach resulted in obtaining high precision for both calibration and validation periods and the simulation show remarkable consistency. Also, the one-way sensitivity analysis indicates that the longitudinal dispersivity is more sensitive than the effective porosity in this simulation. The investigation of the spatial distribution of the estimated longitudinal dispersivity by the combined approach indicates that the value of the parameter has a decreasing trend from the south to the north (50 to 8 m) in the aquifer environment which is consistent with the changes in the characteristics of porous media in this study area, and therefore it concludes that the combined approach provides a reliable and appropriate estimation of the spatial distribution of longitudinal dispersivity.

Recurrence rate of renal cell carcinoma in the lungs after five years of nephrectomy is 93%. The occurrence of RCC after 16 years of nephrectomy as pulmonary metastasis is rare and needs to be considered in patient presenting with pulmonary nodules after a long interval since nephrectomy.

Key Points : • Interventional therapies directed at fenestration closure in the Fontan patient must rely on good hemodynamic data • The Large Optimus-CVSTM stent is an additional armamentarium for fenestration closure however, longer term follow up is needed • Multi institutional studies defining the long-term benefits of fenestration closure and outlining fenestration management guidelines may help improve the long-term morbidity and mortality in this group of patients.

Peptides play a key role in controlling many physiological and neurobiological pathways. Many bioactive peptides require a C-terminal α-amide for full activity. The bifunctional enzyme catalyzing α-amidation, peptidylglycine α-amidating monooxygenase (PAM), is the sole enzyme responsible for amidated peptide biosynthesis, from Chlamydomonas reinhardtii to Homo sapiens. Many neuronal and endocrine functions are dependent upon amidated peptides; additional amidated peptides are growth promoters in tumors. The amidation reaction occurs in two steps, glycine α-hydroxylation followed by dealkylation to generate the α-amide product. Currently, most potentially useful inhibitors target the first reaction, which is rate-limiting. PAM is a membrane-bound enzyme that visits the cell surface during peptide secretion. PAM is then used again in the biosynthetic pathway, meaning that cell-impermeable inhibitors or inactivators could have therapeutic value for the treatment of cancer or psychiatric abnormalities. To date, inhibitor design has not fully exploited the structures and mechanistic details of PAM.

COVID-19 Vaccines Tolerated in Patients with Paclitaxel and Docetaxel Allergy

Objective: To compare outcomes data of obese and non-obese pediatric patients with acute promyelocytic leukemia from the Cancer and Leukemia Group B trial C9710 and the Children’s Oncology Group trial AAML0631. Methods: Data including demographics, adverse events, overall survival and event free survival was analyzed, with a focus on mortality in obese patients. Results: The incidence of obesity was 34% on C9710 and 35% on AAML0631. There was significantly lower overall survival in the obese population on AAML0631. Thirteen patients died during therapy or in follow up; seven of these occurred during induction. Conclusion: The incidence of obesity is higher in patients with APL compared to the general population. The presence and degree of obesity can influence OS on the most current treatment regimen. This implies the need for close management of obese patients at diagnosis as well as reinforces the need for further research on obesity driven APL

Heterogeneous seascapes and strong environmental gradients in coastal waters are expected to influence adaptive divergence, particularly in species with large population sizes where selection is expected to be highly efficient. However, these influences might also extend to species characterized by strong social structure, natal philopatry and small home ranges. We implemented a seascape genomic study to test this hypothesis in Indo-Pacific bottlenose dolphins (Tursiops aduncus) distributed along the environmentally heterogeneous coast of southern Australia. The datasets included oceanographic and environmental variables thought to be good predictors of local adaptation in dolphins and 8,081 filtered single nucleotide polymorphisms (SNPs) genotyped for individuals sampled from six different bioregions. From a neutral perspective, population structure and connectivity of the dolphins were generally influenced by habitat type and social structuring. Genotype-environment association analysis identified 241 candidate adaptive loci and revealed that sea surface temperature and salinity gradients influenced adaptive divergence in these animals at both large- (1,000s km) and fine-scales (<100 km). Enrichment analysis and annotation of candidate genes revealed functions related to sodium-activated ion transport, kidney development, adipogenesis and thermogenesis. The findings of spatial adaptive divergence and inferences of putative physiological adaptations challenge previous suggestions that marine megafauna is most likely to be affected by environmental and climatic changes via indirect, trophic effects. Our work contributes to conservation management of coastal bottlenose dolphins subjected to anthropogenic disturbance and to efforts of clarifying how seascape heterogeneity influences adaptive diversity and evolution in small cetaceans.

Studies of populations oscillating through time have a long history in ecology as these dynamics can help provide insights into the causes of population regulation. A particularly difficult challenge is determining the relative role of deterministic versus stochastic forces in producing this oscillatory behavior. Another classic ecological study area is the study of spatial synchrony which also has helped unravel underlying population dynamic principles. One possible approach to understanding the causes of population cycles is based on the idea that a focus on spatiotemporal behavior, oscillations in coupled populations, can provide much further insight into the relative role of deterministic versus stochastic forces. Using ideas based on concepts from statistical physics, we develop results showing that in a system with coupling between adjacent populations, a study of spatial synchrony provides much information about the underlying causes of oscillations. Novel, to ecology, measures of spatial synchrony are a key step.

Restoration success is often measured by comparing target species abundance between restored and reference populations. Abundance may poorly predict long-term success, however, because seed addition may initially inflate restored population abundances, and reference population abundances may fluctuate with environmental variation. A demographic approach, informed by modern coexistence theory, may allow for more accurate diagnosis of restoration trajectories. We modeled population dynamics of an endangered plant (Lasthenia conjugens) in restored vernal pools and compared them to reference populations over 18 years (2000-2017). Model estimates of L. conjugens growth rates were better predictors of long-term trends than observed abundances. Although populations fluctuated in reference pools, annual rainfall variability acted as a stabilizing factor for L. conjugens. In restored pools however, invasive grasses and associated litter accumulation overrode the benefits of environmental variability. Our approach improves assessment of restoration outcomes and indicates when management actions, such as grass removal, will improve future trajectories.

Abstract Objective: To systematically research the impact of warming needle moxibustion (WNM) for Alzheimer’s Disease (AD). Methods: Four Chinese databases and six English databases were systematically searched. Randomized controlled trials (RCTs) involving the use of WNM to intervene in AD patients were included. Data were extracted from the included studies and methodological quality was evaluated according to the Cochrane Handbook for Systematic Reviews of Intervention 5.1.0. Meta-analysis was performed using RevMan 5.4 software. Results: 8 RCTs comprising 524 patients were included. The study showed that WNM was more effective in the treatment of AD than acupuncture or pharmacotherapy. The findings were as follows: MMSE (MD=1.01, 95%CI: 0.13, 1.90, P=0.03) and CDR (MD=-0.73, 95%CI: -0.84, -0.61, P<0.00001) for global cognitive function, ADL (MD=-1.84, 95%CI: -2.47, -1.22, P<0.00001) for activities of daily living, Syndrome Differentiation Scale of Dementia (SDSD) (MD=-2.67, 95%CI: -3.62, -1.72, P<0.00001), and the total effective rate of patients (OR=3.89, 95%CI: 2.49, 6.09, P<0.00001). The differences in all indicators were statistically significant. Conclusion: WNM has a significant effect on improving cognitive function and daily living ability, reducing the symptoms of AD, and increase the total effective rate. WNM is an effective non-pharmacological therapy for patients with AD. Keywords: Warming needle moxibustion, Alzheimer’s disease, Randomized Controlled Trials, systematic review and meta-analysis

Achieving global sustainability goals requires most people and societies to fundamentally alter their relationship with nature. New approaches are called for to guide change processes towards sustainable futures that embrace the plurality of people’s perspectives on nature. This paper presents a novel approach to exploring desirable futures for nature and people that was developed through an application in National Park Hollandse Duinen in the Netherlands. This new national park is developed bottom-up by a diverse group of actors reshaping their interactions with each other and with nature. Our approach, co-designed with key stakeholders of the national park, engages with a new pluralistic framework for nature values presented by the IPBES task force on scenarios and models to catalyze the development of nature-centered scenarios. We integrated this Nature Futures Framework with the Three Horizons Framework in a participatory workshop process designed to bring people’s diverse relationships with nature to the fore, and jointly envision desirable futures and the pathways to get there. An analytical framework is used to analyze and compare the visions and assess their potential contribution to the SDGs. We summarize the results of the application in National Park Hollandse Duinen and reflect on lessons learned. We see much potential for this values-based futures approach to support change processes in various social-ecological contexts toward more sustainable futures for nature and people.

Predators can strongly influence disease transmission and evolution, particularly when they prey selectively on infected hosts. Although selective predation has been observed in numerous systems, why predators select infected prey remains poorly understood. Here, we use a model of predator vision to test a longstanding hypothesis as to the mechanistic basis of selective predation in a Daphnia-microparasite system, which serves as a model for the ecology and evolution of infectious diseases. Bluegill sunfish feed selectively on Daphnia with a variety of parasites, particularly in water uncolored by dissolved organic carbon. The leading hypothesis for selective predation in this system is that infection-induced changes in the appearance of Daphnia render them more visible to bluegill. Rigorously evaluating this hypothesis requires that we quantify the effect of infection on the visibility of prey from the predator’s perspective, rather than our own. Using a model of the bluegill visual system, we show that the three common parasites, Metschnikowia bicuspidata, Pasteuria ramosa and Spirobacillus cienkowskii, increase the opacity of Daphnia, rendering infected Daphnia darker against the background of downwelling light. As a result of this increased brightness contrast, bluegill can see infected Daphnia at greater distances than uninfected Daphnia – between 19-33% further, depending on the parasite. Pasteuria and Spirobacillus also increase the chromatic contrast of Daphnia. Contrary to expectations, the visibility Daphnia was not strongly impacted by water color in our model. Our work generates hypotheses about which parasites are most likely affected by selective predation in this important model system and establishes visual models as a valuable tool for understanding ecological interactions that impact disease transmission.

Background In critical care patients, the nutritional status is related to many factors such as existing co-morbidities, nutritional history, and the current disease. It is crucial to apply a comprehensive nutritional assesment and to start nutritional support as soon as possible in intensive care unit(ICU) where malnutrition is common. There are many studies on association between modified Nutritional Risk in Critical Patients (mNUTRIC) score and outcome in ICU patients but the effectiveness of tools for risk assesment isn’t still remains unclear. We aimed to define the correlation between the mNUTRIC score and 28-day mortality in patients with chronic obstructive pulmonary disease (COPD) in ICU. Materials and Methods The admission of COPD patients to the respiratory ICU in 2018 were determined retrospectively. Demograpic data of all patients, body mass index (BMI), mNUTRIC scores, Acute Physiology and Chronic Health Assessment II (APACHE II), Sequential Organ Failure Assessment (SOFA) scores, Charlson Comorbidity Index (CCI), time from patient ward to ICU admission, sepsis parameters including C-reactive protein (CRP) and procalcitonin, ICU length of stay (LOS ICU), vasopressor use, and 28-day mortality were recorded. Results 159 COPD patients involved the study. Age, CCI, day from patient ward to ICU admission, SOFA score, APACHE II score and 28-day mortality were detected to be statistically higher in patients with mNUTRIC ≥ 5 (p < 0.05). Conclusion The mNUTRIC score could be an proper method for nutritional risk to predict prognosis in critically ill COPD patients.

Background Lack of definitive cure for COVID-19 and the late introduction of a vaccine were responsible to push the general public to look for a remedy to treat or prevent COVID-19. The objective of this study was to evaluate patterns and factors that affect self-medication practices in Jordan during the pandemic. Methods This was a cross-sectional study using an online questionnaire that was developed, piloted and distributed to the general public via various social media platforms. The questionnaire assessed the type of drugs and treatments used to self -medicate, the reasons behind their self- medication, and the factors affecting their practices. Results A total of 1179 participants (females 46.4%) with a mean age of 32 (SD=12.5) completed the questionnaire. The overall prevalence of the use of at least one product to treat or prevent COVID-19 was 80.4 %. The most commonly used products to self-medicate were vitamin C (57.6%), followed by paracetamol (51.9%), zinc (44.8%) and vitamin D (32.5%). Female gender (odds ratio [OR]) = 1.603, working in the medical field (OR =1.697), and history of COVID-19 infection (OR =2.026) were variables associated with self-medication. The most common sources of participants’ information about drugs to prevent or treat COVID-19 were newspapers (n=519, 44.0%), followed by pharmacists (43.4%), friends (33.8%) and internet searching such as Google (30.7%). Conclusion This study identified the main drugs and supplements used during COVID-19 and the motives behind their use. It also identified the most influential source of information on the public during the pandemic. Self-medication can lead to worsening of the patient’s health and delay seeking medical advice from healthcare professionals. Efforts should be done to help mitigate risks of self-medications by active involvement of pharmacists and other members of healthcare team to refute false claims about drug, especially in the media.

A document by Fatma Yildirim. Click on the document to view its contents.

Background: The importance of sST2 has been increasingly appreciated because of its associated with the development of heart failure and related diseases. Objective: The aim of this study was to evaluate the association of sST2 with CD4+T cells in patients with organ failure. Methods: 100 (M:F=60:40) organ failure patients aged (mean±SD=69.08±16.68) and 30 (M:F=14:16) normal control aged (mean±SD=60.23±13.99) serum sST2 were detected by chemiluminescence assay (CLIA) and the expression of serum IL-1, IL-6 and TNF-α were analyzed by enzyme-linked immunosorbent assay (ELISA). The proportion of CD4+T cells in peripheral blood was determined by flow cytometry (FCM). Association of sST2 with CD4+T cells in organ failure patents were analyzed by SPASS. Results: The expression of sST2 in organ failure patients (107.4±5.79ng/mL) was significantly higher than normal control (8.57±0.35ng/mL). Inflammatory factors IL-1 and IL-6 in patients were also increased than normal controls (IL-1: 0.33±0.04pg/mL vs 0.14±0.02pg/mL. IL-6: 165.7±10.53pg/mL vs 95.33±7.42pg/mL. TNF-α: 1.57±0.14pg/mL vs 6.11±0.77pg/mL). In patients, the results showed CD4+T cells were reduced compare with normal control (238.3±13.67/μL vs 1081±39.13/μL). Additionally, sST2 was found to be inversely associated with CD4+T cell in patients with organ failure. Conclusion: sST2 level was closely related to the development of organ failure and sST2 was obviously correlated with CD4+T cell in patients with organ failure.

Background: Epitope mapping is an increasingly important aspect of biotherapeutic and vaccine development. Recent advances in therapeutic antibody design and production has enabled candidate mAbs to be identified at a rapidly increasing rate resulting in a significant bottleneck in the characterization of ‘structural’ epitopes, that are challenging to determine using existing high throughput epitope mapping tools. Here, Hydrogen/Deuterium Exchange Mass Spectrometry (HDX-MS) epitope screening workflow was introduced that is well suited for accelerated characterization of epitopes with a common antigen. Main methods and major results: The method is demonstrated on set of 6 candidate mAbs targeting Pertactin (PRN). Using this approach, five of the six epitopes was unambiguously determined using two HDX mixing timepoints in 24 hours total run time, corresponding to substantial decrease in the instrument time required to map a single epitope using conventional HDX workflows. Conclusion: An accelerated HDX-MS epitope screening workflow was developed. The two-timepoint ‘screening’ workflow mapped all six mAbs and generated high confidence epitopes for five of the six mAbs assayed. The substantial improvement in the rate of data collection can advance HDX-MS for higher throughput investigations supporting the ability to evaluate a broader number of mAb candidates at an earlier stage of vaccine development.

The COVID-19 pandemic has led to unprecedented economic and health vulnerability and inequities globally. This study aims to determine the out-of-pocket (OOP) expenditure of families of children with cancer in Peru before and during the COVID-19 pandemic. We conducted a cross-sectional survey of 235 parents and caregivers of children diagnosed with cancer in Peru. Our study suggests that OOP expenses in these families constitute a catastrophic expense for health. This situation was aggravated due to a decrease in the economic income for most families due to the disruption in formal and informal employment.

Metastatic tumors to the heart include lymphomas, sarcoma, leukemia, and melanoma. Of these, metastatic melanoma is the most common, and are usually hematogenous, where metastatic lesions can be present in the left ventricle, right atrium, and/ or the right ventricle. We present an atypical metastatic melanoma pattern, where cardiac metastasis originated by direct extension from the adjacent gastric mesentery. We also present our trans-cardiac resection approach, which was the safest way to access the cardiac metastasis intra-operatively without disrupting the tumor.

Objective We performed a retrospective analysis to investigate the clinical characteristics and therapeutic strategies of 20 refractory/recurrent PNH patients, including the clinical efficacy of chemotherapy treatment and survival. Main Measures The clinical data of 20 classic PNH patients that were refractory/recurrent or had glucocorticoid dependence in our hospital were analyzed, including clinical manifestations, laboratory examinations, treatment efficacy and survival. Key Results Seventeen patients had a marked improvement in anemia after chemotherapy, 14 patients acquired blood transfusion independence, and the Hb of 3 patients increased to normal levels. Although 6 patients still needed blood transfusion, the transfusion interval was significantly prolonged. The percentages of LDH, TBIL and RET, which are indicators of hemolysis, were significantly lower than those before chemotherapy. The dosage of adrenal glucocorticoids was reduced by more than half compared with that before chemotherapy. Conclusions Chemotherapy can reduce PNH clones, promote normal hematopoiesis, and control hemolytic attack. It is a promising and widely used therapeutic method.

NMR studies can provide unique information about protein conformations in solution. In CASP14, three reference structures provided by solution NMR methods were available (T1027, T1029, and T1055), as well as a fourth data set of NMR-derived contacts for a integral membrane protein (T1088). For the three targets with NMR-based structures, the best prediction results ranged from very good (GDT_TS = 0.90, for T1055) to poor (GDT_TS = 0.47, for T1029). We explored the basis of these results by comparing all CASP14 prediction models against experimental NMR data. For T1027, the NMR data reveal extensive internal dynamics, presenting a unique challenge for protein structure prediction. The analysis of T1029 motivated exploration of a novel method of “inverse structure determination”, in which an AF2 model was used to guide NMR data analysis. NMR data provided to CASP predictor groups for target T1088, a 238-residue integral membrane porin, was also used to assess several NMR-assisted prediction methods. Most groups involved in this exercise generated similar beta-barrel models, with good agreement with the experimental data. However, as was also observed in CASP13, some pure prediction groups that did not use the NMR data generated structures for T1088 that better fit the NMR data than the models generated using these experimental data. These results demonstrate the remarkable power of modern methods to predict structures of proteins with accuracies rivaling solution NMR structures, and that it is now possible to reliably use prediction models to guide and complement experimental NMR data analysis.

Objectives: To determine the effectiveness of ciprofloxacin 0.3% antibiotic eardrops in preventing clinically significant postoperative otorrhea and tube obstruction following grommet insertion in children. Design: 3-arm double-blinded randomized controlled trial. Randomisation in 1:1:1 ratio into two interventional and one control arm. The interventional groups received either 5 drops of topical ciprofloxacin 0.3% eardrops in each ear intraoperatively or intraoperatively and for 5 days postoperatively. The control group received no drops. Patients were assessed by blinded assessors at 6 weeks postoperatively. Setting: The study was conducted in a large tertiary health network in Melbourne, Australia. Participants: All children, 17 years and under, undergoing bilateral MEVT surgery with or without concurrent upper airway surgery for recurrent acute otitis media and chronic otitis media with effusion were approached. Main Outcome Measures: Presence of postoperative otorrhea and ventilation tube obstruction at 6 weeks postoperatively. Results: 256 pediatric patients completed the study with a median age of 4.02 years. 153 participants were male. Intraoperative antibiotics were more effective than control in preventing otorrhea (RR=0.341, 95%CI 0.158–0.738, NNT= 11.25, p=.006). Postoperative antibiotics were more effective than control in preventing ventilation tube obstruction (RR=0.424, 95%CI 0.193 to 0.930, NNT=14.7 p=.032). Conclusion: Intraoperative topical ciprofloxacin was effective at preventing early postoperative otorrhea and a prolonged course was effective at preventing ventilation tube obstruction. Future studies on this topic should seek to clarify whether particular subgroups of patients benefit more from prophylactic topical antibiotics and model for cost-effectiveness. Trial Registration: This trial was registered prospectively on the Australian New Zealand Clinical Trials Registry (ACTRN12618001082291) on the 28th of June 2018. Available at URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375306

Introduction: Cardiac implantable electronic devices (CIEDs) induce a foreign body reaction and persistent inflammatory response that produces a fibrotic capsule around the implanted material. The study’s aim was to investigate the ability of small intestinal submucosa (SIS) extracellular matrix (ECM) envelopes to mitigate fibrotic tissue formation and secure devices within healthy, vascularized tissue. Methods: Clinically relevant pacemakers without leads were subcutaneously implanted in a pre-clinical rabbit model. Eleven CIEDs were placed in CanGaroo ECM Envelopes, while ten devices were implanted without envelopes and analyzed at 13 and 26 weeks. The subcutaneous pocket and newly formed connective tissue adjacent to the CIED were evaluated by an independent, blinded pathologist for the local tissue response and constructive remodeling. CIED movement in the pocket was also documented as implant sites were prone to abrasion due to normal rabbit behavior. Results: CanGaroo Envelopes surrounding the CIEDs remodeled into native tissue with normally organized collagen. The tissue had a lower average thickness at 13 and 26 weeks compared to tissue encapsulating CIEDs without envelopes. The tissue also scored significantly higher in neovascularization versus capsule tissue surrounding CIEDs without envelopes at 26 weeks. Use of the ECM envelope reduced the incidence of device flipping within the pocket by 40% compared to CIEDs without envelopes, showing the ability of CanGaroo Envelopes to secure CIEDs in place. Conclusions: CanGaroo ECM Envelopes remodeled into native, vascularized tissue surrounding clinically applicable CIEDs. This thinner, healthy tissue pocket secured CIEDs and significantly improved stabilization versus devices without envelopes over 26 weeks.

Objective The aim of this study is to identify and analyze the gender breakdown of first authorship contributing to the most cited papers in the field of otolaryngology, with a goal towards identifying trends in gender representation in publishing. Methods The top fifty most-cited papers were identified using Science Citation Index of the Institute for Scientific Information. Institution, journal, date of publication, research nature, and subspecialty were extracted for each article. Among the first authors, gender, h-index, percentage of first, last, and corresponding authorship positions, total publications, and citations were analyzed. Results The majority of papers were in the English language, from the United States, of clinical nature, and on otologic topics. Eighty-four percent of papers had men who were first authors although there was no difference in h-index score, authorship position, and number of publications between men and women first authors. Women first authors had significantly more citations (p = 0.02) and average citations/year (p= 0.04) compared to their colleagues. There was no difference in the number of articles with women first authors (p = 0.17) or the total percentage of women authors (p = 0.44) in papers published earlier compared to those published later. Conclusion While a promising number of women otolaryngologists are publishing high-powered articles, future initiatives to promote academic productivity and inclusivity should be considered.