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PROTECTING A HERITAGE-SITE GROUNDWATER-DEPENDENT  POND USING TRANSIENT MODFLOW SCENAR...
Muhammad Hasan

Muhammad Hasan

February 26, 2026
A groundwater-dependent sacred pond at the Katas Raj heritage site (Salt Range, Pakistan) has experienced declining water levels associated with sustained groundwater abstraction for agriculture, domestic supply, and industrial expansion. To quantify the drivers of decline and evaluate management options, we developed a transient, two-layer MODFLOW model using hydro stratigraphic information, pumping records, and time-varying recharge for 2011-2020, and assessed model performance against available observation-well heads. Water-budget results indicate that current withdrawals exceed natural recharge by approximately 40%, leading to persistent groundwater depletion and an average drawdown of about 0.5 m/year in the vicinity of the pond, with larger localized declines under future stress scenarios. Scenario testing shows that stabilizing groundwater levels near the pond requires an approximately 40% reduction in abstraction relative to current conditions. Managed Aquifer Recharge (MAR) implemented through infiltration ponds provides a complementary intervention, supplying an estimated 13,333 m³/day of infiltration and reducing the modelled water-budget deficit by roughly 60%. These findings translate model outputs into actionable thresholds for pumping control and MAR sizing to protect groundwater-dependent heritage water bodies under increasing demand and recharge stress, and provide a scenario-based workflow applicable to similar settings facing competing groundwater uses.
COVID-19 and late-onset hypertension with hyporeninaemic hypoaldosteronism
Amit Mandal
Jason Kho

Amit Mandal

and 3 more

September 28, 2020
COVID-19 and late-onset hypertension with hyporeninaemic hypoaldosteronismAmit K J Manda, MB, FRCP(Ed), FRCP, FACP1Jason Kho MBBCh, BAO1Sofia Metaxa, MD, PhD 1Constantinos G Missouris, MD, FRCP, FACP1,21Wexham Park Hospital, Frimley Health NHS Foundation Trust, UK2University of Cyprus Medical School, Nicosia, Cyprus
Efficacy of Urinary Mast Cell Mediators in Patients with Primary High-Grade Non-Muscl...
Muhammed Fatih Simsekoglu
Islim  Kaleler

Muhammed Fatih Simsekoglu

and 6 more

September 28, 2020
Background: Mast cells play a critical role in tumor-associated immune pathways. We aimed to prospectively investigate the urinary mast cell mediators in patients with non-muscle invasive bladder cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG) immunotherapy. Methods: Nineteen patients who have received immunotherapy due to NMIBC and 19 healthy participants were enrolled. Urine samples were collected to assay N-methylhistamine, histamine and tryptase levels immediately before the first BCG instillation, immediately after the third and sixth instillations, and four weeks after the sixth instillation in patients with NMIBC and at a single visit in healthy participants. Cystoscopic examinations were performed on the patient with NMIBC at three-month intervals for two years. The changes in urinary markers due to BCC response, BCG instillation, and the presence of NMIBC were assessed. Results: The average age was 56.1 ± 10.5 years in patients with NMIBC. Fourteen patients had high-grade Ta tumors, and 5 had high-grade T1 tumors. While 12 patients responded, 6 presented with recurrence and 1 with progression. There was no correlation between the levels of mast cell mediators and BCG response. The N-methylhistamine and histamine levels were increased significantly with the onset of immunotherapy and N-methylhistamine levels were decreased significantly when immunotherapy was terminated. Pre-BCG estimated marginal means of N-methylhistamine were significantly higher in patients with NMIBC than healthy participants. Conclusions: This is the first study to determine that urine histamine and N-methylhistamine levels showing the change with immunotherapy. However, these mediators were not found to predict the patients’ response to immunotherapy.
Clinical Outcomes of Radical Surgery in Patients with Renal Carcinoma and Associated...
Bulent Onal
Muhammed Fatih Simsekoglu

Bulent Onal

and 5 more

September 28, 2020
Background: Renal carcinoma and associated venous thrombosis cause-specific perioperative and postoperative challenges. We aimed to evaluate the factors affecting clinical outcomes in patients undergoing radical surgery due to renal carcinoma and associated venous thrombosis. Materials and methods: Hospital records were retrospectively reviewed to identify patients with renal carcinoma and associated venous thrombosis treated with radical surgery between 2006 and 2019. Preoperative, perioperative, and postoperative findings were analyzed to determine the associations between clinical and survival outcomes. Overall and disease-free survival was analyzed by the Kaplan-Meier method. Other associated prognostic variables were assessed using univariate and multivariate Cox regression analyses. Results: Thirty-three patients with renal carcinoma and associated venous thrombosis were enrolled for this study. There were 15 (45.4%) patients with level I, five (15.2%) with level II, eight (24.2%) with level III, and five (15.2%) with level IV venous thrombosis according to the Mayo Clinic classification system. The median follow-up was 35.6 months. In the univariate analysis, increased tumor size was associated with poor overall and disease-free survival. Preoperative clinic M1 disease was associated with poor overall survival. A high Mayo Clinic thrombus level was associated with poor disease-free survival. In the multivariate analysis, only tumor size and clinic M1 disease were independently correlated with poor overall survival. No independent statistically significant association was detected between thrombus level and survival outcomes. Conclusions: Although the thrombus level was not associated with overall and disease-free survival, tumor size and clinic M1 disease were found to have an independent prognostic impact on overall survival.
Comparison of glucocorticoids and painkiller prescribed days between rheumatoid arthr...
Zon-Min  Lee
Yao-Hsu Yang

Zon-Min Lee

and 5 more

September 28, 2020
Comparison between early biologics treatment and late biologics treatment of rheumatoid arthritis (RA) patients in decreasing prescription days of glucocorticoids and painkillers by using the Taiwan National Health Insurance Research database from January 1, 1997 to December 31, 2013. We defined early use of biologics as biologics prescribed within 2.24 years after the RA diagnosis, and the late use of biologics was defined as those prescribed after 2.24 years of the RA diagnosis. These definitions are based on previous studies defining early arthritis as arthritis within 2 years of diagnosis, while we needed another 3 months for application biologics here in Taiwan, which equals a total of 2.24 years. Among the 821 patients, 410 patients (50%) were classified in the Early group, and the other 411 patients (50%) were classified in the Late group. The use of any of these three types of medication, including steroids, disease modifying antirhuematic drugs, and nonsteroid anti-inflammatory drug (NSAID) was changed significantly after biologics treatment. Comparing between before and after biologics treatment, oral medication was significantly tapered (all p <0.0001). The results show that men are 1.81 times more likely than women to taper oral glucocorticoids and NSAIDs. Younger age (<45) patients are 1.91 times more likely to taper steroids and NSAIDs than those aged over 65 years old. Both gender and age were found to be independent factors that could decrease days of prescription of both steroids and NSAIDs in early use of biologics agents. This study indicates that younger patients only need short-term (2.53±1.92 years, p=0.03) and early treatment with biologics (within 2.24 years of diagnosis of RA), just in order to taper steroids and NSAIDs to less than 50% than before biologics treatment.
Diversity of functional alterations of the ClC-5 exchanger in the region of the proto...
Imène Sakhi
Yohan Bignon

Imène Sakhi

and 7 more

September 28, 2020
Mutations in the CLCN5 gene encoding the 2Cl-/1H+ exchanger ClC-5 are associated with Dent disease 1, an inherited renal disorder characterized by low molecular weight (LMW) proteinuria and hypercalciuria. In the kidney, ClC-5 is mostly localized in proximal tubule cells where it is thought to play a key role in the endocytosis of LMW proteins. Here, we investigated the consequences of eight previously reported pathogenic missense mutations of ClC-5 surrounding the “proton glutamate” that serves as a crucial H+-binding site for the exchanger. A complete loss of function was observed for a group of mutants that were either retained in the endoplasmic reticulum of HEK293T cells or unstainable at plasma membrane due to proteasomal degradation. In contrast, the currents measured for a second group of mutations in X. laevis oocytes were reduced. Molecular Dynamics simulations performed on a ClC-5 homology model demonstrated that such mutations may alter ClC-5 protonation by interfering with the water pathway. Analysis of clinical data from patients harboring these mutations demonstrated no phenotype/genotype correlation. This study reveals that mutations clustered in a crucial region of ClC-5 have diverse molecular consequences in patients with Dent disease 1, ranging from altered expression to defects in transport.
Stability analysis and optimal control of avian influenza model on complex networks
keguo ren
zhang qimin

keguo ren

and 2 more

September 26, 2020
In this paper, an avian influenza model with saturation and psychological effect on heterogeneous complex networks is proposed. Firstly, the basic reproduction number $\mathscr{R}_{0}$ is given through mathematical analysis, which is a threshold to determine whether or not the disease spreads. Secondly, the locally and globally asymptotical stability of the disease-free equilibrium point and the endemic equilibrium point are investigated by using Lyapunov functions and Kirchhoff’s matrix tree theorem. If $\mathscr{R}_{0}<1$, the disease-free equilibrium is globally asymptotically stable and the disease will die out. If $\mathscr{R}_{0}>1$, the endemic equilibrium is globally asymptotically stable. Thirdly, an optimal control problem is established by taking slaughter rate and cure rate as control variables. Finally, numerical simulations are given to demonstrate the main results.
Transcriptomics of epidermal mucus as a nonlethal method to compare gene expression v...
Nicolette Andrzejczyk
Lee Hrenchuk

Nicolette Andrzejczyk

and 3 more

September 28, 2020
Although transcriptomic analysis of wild organisms is a powerful tool to understand molecular differences among populations, most methods require the use of lethal sampling. In fish, the use of epidermal mucus is a promising method for development of nonlethal sampling tools. Previous studies have shown that mRNA is dynamically regulated in fish epidermal mucus following stressor exposure, suggesting that mucus is reflective of molecular changes occurring within the organism in response to its environment. The aim of the study was to determine whether transcriptomics of mucus could discern molecular differences among populations of lake trout. In order to do so, mucus was collected and sequenced from four geographically-distinct lake trout (Salvelinus namaycush) populations at the IISD Experimental Lakes Area. Principal component analysis (PCA) and hierarchical clustering of read data showed that each lake trout population had unique transcriptomic profiles, suggesting that RNA sequencing of mucus is able to discern molecular differences among fish populations. Furthermore, differential gene expression analysis identified regulation of immune-related transcripts and viral gene expression transcripts among populations. PCA and a mixed linear model of water quality parameters indicated that environmental variables accounted for transcriptomic variation among populations. However, 32% of transcriptomic variance was unaccounted for by the mixed linear model, suggesting that other variables may influence transcription, such as epigenetics and presence of pathogens. Overall, results indicate that RNA sequencing of epidermal mucus is an effective, nonlethal method to study transcriptional differences among fish populations and may be especially useful for studies of endangered species.
Altered hippocampal kynurenine pathway metabolism contribute to hyperexcitability in...
Soumil Dey
Aparna Banerjee Dixit

Soumil Dey

and 7 more

September 28, 2020
Background and Purpose Glutamate receptor mediated enhanced excitatory neurotransmission is typically associated with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Kynurenic acid (KYNA) and quinolinic acid (QUIN) are two important tryptophan-kynurenine pathway (KP) metabolites that modulate glutamate receptor activity. This study was designed to test the hypothesis that alteration in metabolism of KP metabolites in the hippocampus of patients with MTLE-HS contributes to abnormal glutamatergic transmission. Experimental Approach TKP metabolites level were determined using HPLC and LC-MS/MS in the hippocampal samples of patients with MTLE-HS compared to autopsy and non-seizure control samples. mRNA and protein expression of TKP enzymes were determined by qPCR and western blot. Spontaneous glutamatergic activities were recorded from pyramidal neurons in presence of kynurenine (KYN) and KYNA using whole cell patch clamp. Key Results We observed significantly reduced KYNA and elevated QUIN levels in the hippocampal samples, while KYN level remains unaltered. Spontaneous glutamatergic activity in the hippocampal samples was higher compared to that in non-seizure controls. Treatment with kynurenine inhibited the glutamatergic activity in non-seizure control samples but not in case of the hippocampal samples. However, exogenously applied KYNA inhibited glutamatergic activity in both non-seizure control and hippocampal samples. We also observed reduced levels of enzyme kynurenine aminotransferase II and its co-factor pyridoxal phosphate in the hippocampal samples. Conclusion Our findings indicate that altered metabolism of TKP metabolites in hippocampus could contribute to hyperglutamatergic tone in patients with MTLE-HS.
REVIEW OF PHARMACOLOGICAL OPTIONS FOR THE TREATMENT OF CHAGAS DISEASE
Fernanda Lascano
Facundo Garcia-Bournissen

Fernanda Lascano

and 2 more

September 28, 2020
Introduction: Chagas disease (CD) is a worldwide problem, with over 8 million people infected in both rural and urban areas. CD was first described over a century ago, but only two drugs are currently available for CD treatment, benznidazole (BZN) and nifurtimox (NF). Treating CD infected patients, especially children and women of reproductive age, is vital in order to prevent long term sequelae such as heart and gastrointestinal disfunction, but this aim is still far from being accomplished. Currently, the strongest data to support benefit-risk considerations come from trials in children. Finally, treatment response biomarkers need further development as serology is being questioned as the best method to assess treatment response. Areas covered: This article is a narrative review on the pharmacology of drugs for CD, particularly BZN and NF. Data on drug biopharmaceutical characteristics, safety and efficacy of both drugs are summarized from a clinical perspective. Current data on alternative compounds under evaluation for CD treatment, and new possible treatment response biomarkers are also discussed. Conclusion: Early diagnosis and treatment of CD, especially in pediatric patients, is vital for an effective and safe use of the available drugs (i.e. BZN and NF). New biomarkers for CD are urgently needed for the diagnosis and evaluation of treatment efficacy, and to guide efforts from academia and pharmaceutical companies to accelerate the process of new drugs development.
Favourable pharmacokinetics of intradermal adalimumab over subcutaneous administratio...
Justin Jacobse
Wouter  ten Voorde

Justin Jacobse

and 21 more

September 28, 2020
Aim To evaluate feasibility of intradermal (i.d.) adalimumab administration using hollow microneedles, and to compare a single i.d. dose of adalimumab using a hollow microneedle with a single subcutaneous (s.c.) dose using a conventional needle. Methods In this single-centre double-blind, placebo-controlled, double-dummy clinical trial in 24 healthy adults we compared 40 mg adalimumab (0.4 mL) administered i.d. using a hollow microneedle with a s.c. dose using a conventional needle. Primary parameters were pain, acceptability, and local tolerability; secondary parameters safety, pharmacokinetics and immunogenicity. We explored usability of optical coherence tomography (OCT), clinical photography, thermal imaging, and laser speckle contrast imaging (LSCI) to evaluate skin reaction after i.d. injections. In vitro protein analysis was performed to assess compatibility of adalimumab with the hollow microneedle device. Results While feasible and safe, injection pain of i.d. adalimumab was higher compared to s.c. adalimumab (35.4 vs. 7.9 on a 101-point VAS scale). Initial absorption rate and bioavailability were higher after i.d. adalimumab (Tmax=95h(47-120); F=129%(6.46%)) compared to s.c. adalimumab (Tmax=120h(96-221)). In 50% and 83% of the subjects anti-adalimumab antibodies were detected after i.d. and s.c. adalimumab, respectively. We observed statistically significantly more erythema and skin perfusion after i.d. adalimumab, compared to s.c. adalimumab and placebo injections (p<0.0001). Cytokine secretion after whole blood LPS challenge was comparable between administration routes. Conclusion Intradermal of adalimumab using hollowing microneedles was perceived as more painful, and less accepted than s.c. administration, however, yields a higher bioavailability with similar safety and pharmacodynamic effects.
Comment on “The changing face of paracetamol toxicity and new regimens for an old ant...
Alaa Daoud
Kim Dalhoff

Alaa Daoud

and 2 more

September 28, 2020
Comment on “The changing face of paracetamol toxicity and new regimens for an old antidote acetylcysteine”Dear Editor,We have with interest read the recently published commentary by Isbister and Chiew1 in which current approaches for the treatment of paracetamol (PCM) poisoning with N-acetylcysteine (NAC) were described. While we appreciate the authors’ valuable comments on the challenges in managing this common poisoning, we noticed the omission of the Danish NAC regimen.NAC has been established as a highly efficient antidote in preventing PCM-induced hepatotoxicity when administered within 8 h of PCM ingestion.2 Treatment delays because of pending laboratory results do not harmfully affect the outcome if NAC is administered within 8 h. However, it is frequent occurring that patients get treated beyond that time in e.g. the UK,3 thus potentially decreasing the efficacy of NAC.In Denmark a 20-hour two-bag regime has been used for more than seven years.4 All patients suspected of poisoning with more than 6 g PCM are treated with NAC without risk stratification according to a nomogram. Patients deliberately poisoning themselves with PCM may not report reliable information of the time of ingestion and dose of PCM. If a nomogram is used without an accurate time of ingestion, the estimation of the risk of hepatotoxicity is unreliable. It is well documented that patients have been withheld treatment with NAC due to misinterpretation of the nomogram resulting in hepatotoxicity.5Concomitant overdosing of several drugs that delay the time to peak PCM concentration is common and may result in crossing from below to above the treatment line5 leaving line crossers who required treatment untreated. The same is relevant in cases of massive PCM overdosing alone (drug bezoar) or poisonings with extended-release PCM formulations (late PCM peak).6 Furthermore, it is well-known that the half-life of PCM in liver injury exceeds the expected 4 h used for treatment decision in the nomogram, thus further questioning the reliability of the nomogram as a risk stratification tool for patients suffering from liver diseases. Although the Danish regime further reduces the risk of hepatoxicity, because of incorrectly withheld or delayed NAC treatment compared to other regimes based on a nomogram, it comes at a cost of more patients being treated.We believe that all approaches deserve mention in order to identify the most effective and safe approach to this poisoning. Therefore, we should consider the effectiveness, duration and safety of choice of treatment including the incidence of anaphylactoid reactions to NAC while assuring that nobody is wrongly withhold NAC treatment. Not to mention, that the abovementioned approach is associated with a comparable incidence of anaphylactoid reactions when compared to other approaches.4,7 It is worth mentioning that the primary factor limiting a faster delivery of the antidote is the development of anaphylactoid reactions. It is to be shown if pre-administrations of antihistamines can reduce the dose-dependent side-effect leading to development of faster NAC regimes7.We declare no competing interests.Alaa Daoud (orcid: 0000-0002-8714-4028)a,b, Kim Peder Dalhoffa,b, Tonny Studsgaard Petersen (orcid: 0000-0002-9974-2738)a,baDepartment of Clinical Medicine, Faculty of Health and Medical science, Copenhagen University, Copenhagen, DenmarkbDepartment of Clinical Pharmacology and The Danish Poison Information Centre, Bispebjerg and Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark*Correspondence to Alaa Daoud, Alaa.Ahmed.Daoud@regionh.dk1. Isbister GK, Chiew A. The changing face of paracetamol toxicity and new regimens for an old antidote acetylcysteine. British Journal of Clinical Pharmacology . n/a(n/a). doi:10.1111/bcp.144952. Prescott LF, Illingworth RN, Critchley JA, Stewart MJ, Adam RD, Proudfoot AT. Intravenous N-acetylcystine: the treatment of choice for paracetamol poisoning. Br Med J . 1979;2(6198):1097-1100. doi:10.1136/bmj.2.6198.10973. The College of Emergency Medicine. Paracetamol Overdose Clinical Audit 2013-14. Accessed September 7, 2020. https://www.rcem.ac.uk/docs/Previous%20Audits/CEM8120-Paracetamol%20Overdose%20national%20report.pdf4. Daoud A, Dalhoff KP, Christensen MB, Bøgevig S, Petersen TS. Two-bag intravenous N-acetylcysteine, antihistamine pretreatment and high plasma paracetamol levels are associated with a lower incidence of anaphylactoid reactions to N-acetylcysteine. Clinical Toxicology . 2020;58(7):698-704. doi:10.1080/15563650.2019.16758865. Mutsaers A, Green JP, Sivilotti MLA, et al. Changing nomogram risk zone classification with serial testing after acute acetaminophen overdose: a retrospective database analysis. Clinical Toxicology . 2019;57(6):380-386. doi:10.1080/15563650.2018.15293206. Bizovi KE, Aks SE, Paloucek F, Gross R, Keys N, Rivas J. Late Increase in Acetaminophen Concentration After Overdose of Tylenol Extended Relief. Annals of Emergency Medicine . 1996;28(5):549-551. doi:10.1016/S0196-0644(96)70119-17. Mullins ME, Yu M, O’Grady L, Khan S, Schwarz ES. Adverse reactions in patients treated with the one-bag method of N-acetylcysteine for acetaminophen ingestion. Toxicology Communications . 2020;4(1):49-54. doi:10.1080/24734306.2020.1770498
ANXIETY AND EATING DISORDERS DURING THE QUARANTINE OF COVID-19: AN OBSERVATIONAL STUD...
Dr. Idiberto Jose Zotarelli Filho, MSc, Ph.D

Dr. Idiberto Jose Zotarelli Filho, MSc, Ph.D

September 29, 2020
Beatriz Colovati Saccardo1, Camila Saggioro Paulucci¹,  Pedro Saggioro Paulucci 1, Heloisa Dias Sanson¹, Otávio Carbone Ruy¹, Durval Ribas Filho1,2, Ana Valéria Garcia Ramirez2,5, Idiberto José Zotarelli Filho2,3,4 1.      FAMECA, Faculty of Medicine of Catanduva - Padre Albino University Center, Catanduva/SP, Brazil.2.      Associação Brasileira de Nutrologia (ABRAN)/Brazilian Association of Nutrology, Catanduva/SP, Brazil.3.      FACERES – Faculdade de Medicina de São José do Rio Preto/SP, Brazil.4.      Zotarelli-Filho Scientific Work, São José do Rio Preto/SP, Brazil.5.      Ana Valeria Ramirez Clínica- Clinic of Nutrition and Health Science, São José do Rio Preto SP, Brazil.  Corresponding Author: Dr. Idiberto José Zotarelli Filho, MsC, Ph.D. FACERES- Medical School, São José do Rio Preto SP, Brazil; email: dr.idibertozotarelli@faceres.com.br  
Novel technique for safe tracheostomy during COVID-19 pandemic using Evone® flow-cont...
Natalia Magasich-Airola
Maria Rosal

Natalia Magasich-Airola

and 3 more

September 25, 2020
A document by Natalia Magasich-Airola. Click on the document to view its contents.
Improved stillbirth risk stratification, an urgent global need. (Mini-commentary on B...
Jessica Page

Jessica Page

September 28, 2020
Mini-commentary on BJOG-20-0453.R1: Can risk prediction models help us individualise stillbirth prevention? A systematic review and critical appraisal of published risk models
Attention-Deficit/Hyperactivity Disorder in Children Following Prenatal Exposure to A...
Angela Lupattelli
Milada Mahic

Angela Lupattelli

and 5 more

September 28, 2020
Objective: To quantify the association between prenatal exposure to selective serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitor antidepressants and ADHD in offspring, with quantification of exposure misclassification bias. Design: Norwegian Mother, Father and Child Cohort Study (MoBa), linked to national health registries. Setting: Norway. Population: 6395 children born to women who self-reported depression/anxiety in pregnancy and were either medicated with SSRI/SNRI in pregnancy (n=818) or non-medicated (n=5228), or did not report depression/anxiety but used antidepressants six months prior to pregnancy (discontinuers, n=349). Main outcome measure: Diagnosis of ADHD or redeemed prescription for ADHD medication in children, and mother-reported symptoms of ADHD at child age five years. Results: When the hazard was averaged over the duration of the study’s follow-up, there was no difference in ADHD risk between ever in-utero SSRI/SNRI-exposed children and comparators (weighted Hazard Ratio (wHR): 1.07, 95% Confidence Interval (CI): 0.76-1.51, vs. non-medicated; wHR: 1.53, 95% CI: 0.77-3.07, vs. discontinuers). Underestimation of effects due to exposure misclassification was modest. At early childhood, the risk for ADHD was lower with prenatal SSRI/SNRI exposure compared with non-medicated, and so were ADHD symptoms (weighted β: -0.23, 95% CI: -0.39, -0.08); this risk became elevated at child age 7-9 years (wHR: 1.93, 95% CI: 1.22-3.05). Maternal depression/anxiety prior to pregnancy was independently associated with child ADHD. Conclusion: Prenatal SSRI/SNRI exposure is unlikely to considerably increase the risk of child ADHD beyond that posed by the underlying psychiatric illness. The elevated risk at child age 7-9 years needs to be further elucidated.
Health-related Quality of Life and Quality of Care in pregnant and postnatal women du...
Fátimah  Alaya
Amy P Worrall

Fátimah Alaya

and 5 more

September 28, 2020
Objective To compare self-reported health related quality of life (HRQoL) and quality of care (QoC) received between pregnant and postnatal women during the COVID-19 pandemic at a tertiary unit. Design A prospective case-control study Population Pregnant women, ≥18 years of age, with capacity, who spoke English, and attended the tertiary unit during the pandemic. Methods 18 perinatal women who tested positive for SARS-CoV-2 and 20 asymptomatic control perinatal women were recruited. Demographic characteristics were collected and all participants completed the Short Form (SF-12), Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) and Quality from the Patient’s Perspective (QPP). Means scores in both cohorts were compared. Main Outcome Measures Assessment of psychological distress, HRQoL, QoC and their correlates. Results 95% of the Non-COVID cohort were Caucasian, while 67% of the pregnant women who had COVID-19 were not Caucasian (x2=16.01, p<0.0001). The mean SF-12 for physical health and functionality in the COVID cohort had significantly lower scores (36.54 vs 49.21, 95% CI [6.9 to 20.2], p<0.0002). There was no difference in mental health and wellbeing scores between the COVID and Non-COVID cohorts. The QoC experienced by both cohorts was similar and very positive. Conclusions Among pregnant women who tested positive for COVID-19, there was a significant greater burden on the women’s physical health. Mental health and psychological status was similar in both groups. High quality of care during a pandemic is possible to deliver in a maternity setting, irrespective of the patient’s COVID status.
Provider Views on Sexual and Reproductive Health for Adolescent and Young Adult Women...
Maayan Leroy-Melamed
Seethal Jacob

Maayan Leroy-Melamed

and 3 more

September 28, 2020
Background/Objectives With dramatic improvements in life expectancy, adolescents and young adults (AYA) with sickle cell disease (SCD) increasingly face sexual and reproductive health (SRH) concerns. Despite the high risk of maternal-fetal morbidity and mortality, over half of women with SCD experience pregnancy by age 21, indicating a gap in SRH care. This study examined SCD providers’ practices and attitudes related to SRH, particularly with regards to contraception. Design/Methods We distributed an adapted web-based survey to a national sample of SCD providers to identify their attitudes and practices in addressing SRH with their female patients. We analyzed results using descriptive statistics, independent sample t-tests, Chi-squared and Fishers exact tests. Results Ninety-two SCD providers completed the survey (84% pediatric and 13% adult providers). All respondents rated SRH discussions as moderately important or higher, with the majority (85%) agreeing this care should be standardized. Most respondents (76%) reported discussion of SRH, such as menses, pregnancy, and contraception, with their female patients with SCD at least annually. Although most providers refer SCD patients for birth control (87%), 37% favored the use of hormonal intrauterine devices in this population and 37% the use of injectable contraception among respondents who endorsed a preferred method. Approximately half of respondents (52%) felt the use of combined hormonal contraceptives (CHC) was unacceptable. Conclusion SCD providers consider SRH important for their female patients and largely believe these conversations should be standardized in their clinics. However, the range of conversations and contraceptive recommendations from SCD providers is broad, suggesting that this care can be improved.
Mecânica Clássica - Quadraturas
Mario Cezar Bertin

Mario Cezar Bertin

September 28, 2020
Energia Potencial em uma dimensãoNa seção passada, estudamos o caso da partícula livre. Por não interagir com nenhum outro sistema físico, a partícula livre tem trajetória retilínea, uma vez escolhido um referencial inercial para analisá-la. Para descobrir a curva que representa o movimento, utilizamos o postulado da conservação da energia mecânica e o fato de que a partícula livre só possui energia cinética. Agora, vamos fazer com que esta partícula possa interagir com outros sistemas físicos, mas que ainda tenha seu movimento restrito a uma trajetória retilínea. Na prática, apenas tipos especiais de interação manterão uma partícula em uma única dimensão cartesiana. No entanto, vamos nos utilizar desta situação ideal para introduzir outros conceitos importantes.Vamos supor, agora, um sistema composto de duas partículas de massas \(m_1\) e \(m_2\). A única interação no sistema é a interação entre as duas partículas, portanto, o sistema em si é isolado. Ambas as partículas permanecerão restritas a uma trajetória retilínea, portanto, a interação resulta em movimento unidimensional para cada partícula. Nesta configuração, a energia do sistema é composta pela energia cinética da partícula 1, \(K_1\), da energia cinética da partícula 2, \(K_2\), e da energia de interação \(V_{12}=V_{21}=V\left(x_1,x_2\right)\), denominada energia potencial. No geral, a energia potencial pode depender das posições, velocidades e acelerações de ambas as partículas, mas no caso mais simples, vamos supor que dependa apenas da posição. Assim, temos\[E=K_{1}+K_{2}+V_{12}=\frac{1}{2}m_{1}v_{1}^{2}+\frac{1}{2}m_{2}v_{2}^{2}+V\left(x_{1},x_{2}\right).\] Aqui, os observáveis são vetores em uma dimensão, de modo que podemos ignorar a notação vetorial e trabalhar com o módulo desses vetores.Se o sistema é isolado, esta energia se conserva no tempo, ou seja,\[\frac{dE}{dt}=0\thinspace\thinspace\implies\thinspace\thinspace\left(m_{1}a_{1}+\frac{\partial V}{\partial x_{1}}\right)v_{1}+\left(m_{2}a_{2}+\frac{\partial V}{\partial x_{2}}\right)v_{2}=0.\] Como a trajetória é unidimensional, todos os vetores são colineares, assim, a equação acima pode ser satisfeita de várias formas. A conservação da energia não é suficiente neste caso, porque matematicamente o sistema não é unidimensional. A trajetória o é, mas precisamos de duas variáveis de posição para identificar um estado do sistema em determinado tempo \(t\). Essas variáveis são as posições \(x_{1}\)e \(x_{2}\). Embora o movimento seja unidimensional, dizemos que ele possui dois graus de liberdade. Neste caso, precisaremos de mais um postulado para tratar deste caso, o que deixaremos para a próxima seção.Contudo, uma generalização deste sistema pode ser tratada unidimensionalmente apenas com o sexto postulado, assumindo-se ignorância com relação a uma parte do sistema físico. Considere, por exemplo, uma partícula de massa \(m\) restrita a uma trajetória retilínea, mas que interage com um sistema de partículas, chamado sistema 2. Vamos assumir que não conhecemos nada sobre o sistema interagente, ou seja, não temos informação de sua energia de movimento ou sua energia interna. A energia do sistema completo (partícula + sistema 2) deveria ser a soma:Da energia cinética da partícula 1; Da soma da energia cinética de todas as partículas constituintes do sistema 2;Da interação de cada partícula do sistema 2 com a partícula 1;Da interação interna das partículas do sistema 2.Complicado. Mas em muitos sistemas de interesse é possível modelar a interação do sistema 2 com a partícula 1 com uma única energia potencial \(V\left(x\right)\). Neste caso, estamos ignorando o que ocorre com o sistema 2, já que não temos como ter informações completas sobre ele, e estamos analisando apenas o movimento da partícula 1. Neste caso, a energia relacionada à partícula 1 é dada apenas por\[\label{01}E=\frac{1}{2}mv^{2}+V\left(x\right).\]No geral, não esperamos que esta energia seja conservada, pois estamos deixando de fora o sistema 2. Assim, a partícula 1 passa a ser um sistema aberto, ou não isolado, portanto, o postulado 6 não se aplica. Mas existem sistemas nesta situação que possuem energia (1) conservada. São exemplos de sistemas conservativos.Assim, o sistema descrito pela energia (1) é genuinamente unidimensional, possuindo um único grau de liberdade, representado pela posição \(x\). Se esta energia se conserva, temos\[\frac{dE}{dt}=0\thinspace\thinspace\implies\thinspace\thinspace\left(ma+\frac{\partial V}{\partial x}\right)v=0,\]que resulta em\[\label{02}m\ddot{x}=-\frac{\partial V}{\partial x}.\]equação (2) é o que conhecemos como a equação de movimento do sistema 1.O fato é que é possível modelar a interação sobre um sistema físico de interesse, resultando da interação com um sistema desconhecido, em um grande número de aplicações. Este é o caso, por exemplo, ao analisarmos corpos em queda na Terra. Se o corpo em queda tem massa e dimensões muito menores que a Terra, ele pode ser modelado como uma partícula. A Terra, por outro lado, é um corpo extenso complexo, mas que pode ser modelado por um sistema de partículas, como o sistema 2 acima. Não é necessário conhecer a dinâmica da Terra para estudar a queda do corpo com um alto grau de precisão. Como a interação gravitacional, que rege a interação neste caso, é conservativa, podemos ignorar a Terra e modelar a queda do objeto como o movimento de uma partícula com energia potencial dependente apenas da posição do corpo com relação a uma posição de referência.Assim, cada expressão para \(V(x)\) remonta a um sistema conservativo unidimensional distinto. A partícula livre, tratada na seção passada, é um sistema de potencial zero, ou constante. Note que, se a energia potencial é constante, a energia cinética continua um invariante dinâmico. Como resultado, o acréscimo de um valor constante à energia de uma partícula não muda o movimento da partícula. No caso da partícula livre, basta ver que (2) se resume a \(\ddot{x}=0\) se \(V\) constante, portanto, um potencial constante não resulta em verdadeira interação.A quadraturaVamos supor, agora, o caso de uma partícula restrita a uma reta, sujeita a um potencial que depende apenas da posição dessa partícula na reta, ou seja, \(V=V(x)\). A ausência da velocidade ou da aceleração pode parecer pouco geral, mas o fato é que muitos sistemas de interesse possuem \(V\) como função apenas da coordenada. Neste caso, a energia da partícula é dada pela expressão (\ref{01}). Por enquanto, vamos supor que esta energia se conserva. Assim, \(E\) é uma constante de movimento. Assim como no caso da partícula livre, cada valor de \(E\) definirá uma curva distinta sobre a trajetória retilínea. Vejamos como isso ocorre.Da expressão (3), vemos que\[v^{2}=\frac{2}{m}\left[E-V\left(x\right)\right]\thinspace\thinspace\thinspace\implies\thinspace\thinspace\thinspace v=\pm\sqrt{\frac{2}{m}\left[E-V\left(x\right)\right]},\] que dá origem à equação diferencial total\[dx=\pm dt\sqrt{\frac{2}{m}\left[E-V\left(x\right)\right]}.\]Contudo, diferentemente do caso da partícula livre, o lado direito depende de \(x\) em razão da energia potencial. Não é possível simplesmente integrar esta expressão. Mas se considerarmos que o movimento é retilíneo e que, em um subdomínio da curva \(x=x(t)\), a função da curva seja bijetora, teremos, pelo menos para um intervalo \(\Delta t\) definido, uma curva inversa \(t=t(x)\) bem definida. Neste caso, podemos escrever\[\label{04}dt=\pm\sqrt{\frac{m}{2}}\frac{dx}{\sqrt{E-V\left(x\right)}}.\]Caso a curva não tenha inversa única em determinado domínio, podemos quebrar o domínio em partes onde a função \(t=t(x)\) é bem definida. Na expressão (4), vemos que o lado esquerdo depende apenas do tempo, enquanto o lado direito depende apenas da posição. Assim, podemos tomar a integral\[t-t_{0}=\pm\sqrt{\frac{m}{2}}\int_{x_{0}}^{x}\frac{dx'}{\sqrt{E-V\left(x'\right)}}.\]A integral definida, denominada quadratura, pode ser resolvida analiticamente em poucos casos. Mas pode ser sempre trabalhada numericamente ou estimada por métodos aproximativos se a energia potencial for analítica. Vamos supor que, resolvida, a integral resulte em uma função de \(x\). Assim, podemos escrever\[t-t_{0}=\Theta\left(x,E,x_{0}\right),\]em que explicitamos a dependência na energia e na posição inicial. Como \(t=t(x)\) tem uma inversa por definição no domínio \(I=\left[t_0,t\right]\), podemos inverter a expressão acima para obter a curva \(x=\Theta^{-1}\left(x_{0},t_{0},E,t\right).\) Esta é a curva percorrida pela partícula com potencial \(V(x)\) energia constante \(E\) em uma dimensão.O Potencial linear
Predator presence and recent climatic warming raise body temperatures of island lizar...
Felix Landry Yuan
Shun Ito

Felix Landry Yuan

and 6 more

September 28, 2020
In ectothermic predator-prey relationships, the capacity for prey to successfully evade predation will depend upon physiological and behavioural responses that relate to both players’ thermal biology. On the Izu Islands of Japan, we investigated how a prey lizard species has responded physiologically and thermally to the presence of a snake predator over evolutionary time in addition to recent climatic warming. Foraging lizard body temperatures have increased by 1.0°C from 1981 to 2019 while lizard body temperatures were 3.4°C warmer on islands where the snake predator is present relative to snake-free islands. We also found that warmer prey body temperatures result in faster running speeds of the prey at temperatures suboptimal for the snake predator. The results show that lizard body temperatures have increased with warming but not to the same extent as that exerted by predation pressure. However, further warming could irrevocably alter this and other ectothermic predator-prey relationships.
Association between temporary housing habitation after the 2011 Japan earthquake and...
Chiyako Oshikata
Maiko Watanabe

Chiyako Oshikata

and 12 more

September 28, 2020
Background: We previously reported increased prevalence of asthma in adults who lived in temporary housing after the 2011 Great East Japan Earthquake. To investigate changes in asthma prevalence and mite-specific immunoglobulin E (IgE) titers in temporary housing residents from 2014 through 2019. Methods: We diagnosed asthma in Ishinomaki city temporary housing residents (age,  15 years) by using the GINA guidelines. We analyzed serum antigen-specific IgE levels to Dermatophagoides farinae (Der f), Dermatophagoides pteronyssinus (Der p), and Aspergillus fumigatus. Results: The prevalence of asthma exceeded 20% across all age groups throughout the study period. The proportion of study participants with a ‘positive’ antigen-specific IgE titer (i.e.,  0.35 IUA/mL) was higher in asthmatics than in non-asthmatics for Der f and Der p but not for Aspergillus fumigatus. Residents  50 years old who diagnosed asthma or non-asthma, the percentage with Der f -specific IgE titer  0.10 IUA/mL was higher than in those with  0.35 IUA/mL. Among study participants, asthma onset occurred before the earthquake, during residence in shelters or temporary housing, and, after 2016, moving out of temporary housing. The Der p-specific IgE level was positively correlated with the duration of temporary housing (P < 0.05, r = 0.41) and inversely correlated with the time elapsed since moving out of temporary housing (P < 0.05, r = –0.35). Conclusions: Mite allergen sensitization was found in non-asthmatic temporary housing residents after the 2011 Japan earthquake and tsunami; asthma developed even after subjects moved out of temporary housing.
Can plant-soil feedback link genetic diversity and species diversity?
Lana Bolin
Jennifer Lau

Lana Bolin

and 1 more

September 25, 2020
Genetic diversity and species diversity are typically studied in isolation despite theory showing they likely influence one another. Here, we used simplified communities of one or two populations of one or two species to test whether linkages between genetic and species diversity can be mediated by interactions between plants and their soil microbiota, or microbe-mediated plant-soil feedback (PSF). Interspecific PSF promotes the maintenance of species diversity when plants grow better with heterospecific soil microbes than with conspecific microbes. Similarly, intraspecific PSF promotes the maintenance of genetic diversity when plants grow better with heterogenotypic than with congenotypic microbes. We found that genetic diversity reduced the ability of interspecific PSF to maintain species diversity, and, for one study species, species diversity reduced the ability of intraspecific PSF to maintain genetic diversity. If these patterns occur in more diverse communities, then PSF may cause genetic and species diversity to negatively influence one another.
Forest responses to last-millennium hydroclimate variability are governed by spatial...
Christine Rollinson
Andria

Christine Rollinson

and 12 more

September 25, 2020
Forecasts of forest responses to climate variability are governed by climate exposure and ecosystem sensitivity, but ecosystem model projections and process representations are under-constrained by data at multidecadal and longer timescales. Here, we assess ecosystem sensitivity to centennial-scale hydroclimate variability, by comparing dendroclimatic and pollen-inferred reconstructions of drought, forest composition and biomass for the last millennium with five ecosystem model simulations. In both observations and models, spatial patterns in ecosystem responses to hydroclimate variability are strongly governed by ecosystem sensitivity rather than climate exposure. Ecosystem sensitivity was highest in simpler models and higher than observations, suggesting that interactions among biodiversity, demography, and ecophysiology processes dampen the sensitivity of forest composition and biomass to climate variability and change. By integrating ecosystem models with observations from timescales extending beyond the instrumental record, we can better understand and forecast the mechanisms regulating forest sensitivity to climate variability in a complex and changing world.
A network algorithm for the X chromosomal exact test for Hardy-Weinberg equilibrium w...
Jan Graffelman
Leonardo Ortoleva

Jan Graffelman

and 1 more

September 25, 2020
Statistical methodology for testing Hardy-Weinberg equilibrium at X chromosomal variants has recently experienced considerable development. Up to a few years ago, testing X chromosomal variants for equilibrium was basically done by applying autosomal test procedures to females only. At present, male alleles can be taken into account in asymptotic and exact test procedures for both the bi- and multiallelic case. However, current X chromosomal exact procedures for multiple alleles rely on a classical full enumeration algorithm and are computationally expensive, and in practice not feasible for more than three alleles. In this article we extend the autosomal network algorithm for exact Hardy-Weinberg testing with multiple alleles to the X chromosome, achieving considerable reduction in computation times for multi-allelelic variants with up to five alleles. The performance of the X-chromosomal network algorithm is assessed in a simulation study. Beyond four alleles, a permutation test is, in general, the more feasible approach. A detailed description of the algorithm is given and examples of X chromosomal indels and microsatellites are discussed.
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