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The two major urinary metabolites of 14C-timolol in man, involving oxidation and hydrolytic cleavage of the morpholine ring, are also observed in both Sprague-Dawley rats and CRCD-1 mice. These are the N-T(4-[3-(1,1-dimethylethyl)amino]-2-hydroxypropoxy)-1,2,5-thiadiazol-3-ylT-N-(2-hydroxyethyl)glycine and 1-(1,1-dimethylethylamino-3-([4-(2-hydroxyethylamino)-1,2,5-thiadiazol-3-yl]oxy)-2-propanol. The former was previously identified erroneously as the isomeric compound 1-(1,1-dimethylethylamino)-3-([4-(N-2-hydroxyethylglycolamido)-1,2,5-thiadiazol-3-yl]oxy)-2-propanol. Rats and mice had two additional metabolites in common, 1-[(1,1-dimethylethyl)amino]-3-([4-(2-hydroxy-4-morpholinyl)-1,2,5-thiadiazol-3-yl]oxy)-2-propanol and a compound now proposed to be the corresponding morpholino lactone 1-[1,1-dimethylethyl)-amino]-3-([4-(2-oxo-4-morpholinyl)-1,2,5-thiadiazol-3-yl]oxy)-2-propanol but for which the corresponding isomeric morpholino lactam structure 1-[(1,1-dimethylenthyl)-amino]-3-([4-(3-oxo-4-morpholinyl)-1,2,5-thiadiazol-3-yl]oxy))-2-propanol was tentatively proposed in an earlier publication. A metabolite observed in the rat, but not in the other species studied, was 4-(4-morpholinyl)-1,2,5-thiadiazol-3-ol-1-oxide. The metabolic pattern in these rodents does not change significantly after repeated doses. A scheme summarizing the metabolic fate of timolol in man and laboratory animals is presented.

Redox-active polymers (RAPs) are a subclass of polyelectrolytes that can store charge and undergo redox self-exchange reactions. RAPs are of great interest in the field of redox flow batteries (RFBs) due to their ability to quickly charge and discharge, their chemical modularity, and their molecular size. However, designing RAPs for efficient charge transport at the molecular level requires a fundamental understanding of the charge transport mechanisms that occur in RFBs. Previous work from our group has explored these mechanisms, and in this paper, we seek to improve upon the previous model by incorporating both hydrodynamic interactions (HIs) and out-of-equilibrium dynamics, which are both highly pertinent to flow battery systems. We use a hybrid Brownian dynamics and Monte Carlo simulation to model redox-active polymer chains in both dilute and semidilute solutions. This model is used to show that HI is an important feature when charge hopping is not the major mechanism for charge displacement and leads to more rapid segmental and translational motion of polymer chains that expedites charge transport at low polymer concentrations. We demonstrate that strong extensional flows may result in either enhanced or decreased transport depending on the fraction of charges present on the RAP chain. We show that flow not only can promote charge transport by extending polymer conformations but can also suppress nonadjacent charge hopping processes that are important for transport at high charge fractions. Shear flows can similarly enhance charge transport through chain extension, but tumbling dynamics lead to oscillatory displacements that become dominant features with high charge fractions and strong flows.

Transposon-encoded tnpBand iscBgenes encode RNA-guided DNA nucleases that promote their own selfish spread through targeted DNA cleavage and homologous recombination1–4. These widespread gene families were repeatedly domesticated over evolutionary timescales, leading to the emergence of diverse CRISPR-associated nucleases including Cas9 and Cas12 (refs. 5,6). We set out to test the hypothesis that TnpB nucleases may have also been repurposed for novel, unexpected functions other than CRISPR–Cas adaptive immunity. Here, using phylogenetics, structural predictions, comparative genomics and functional assays, we uncover multiple independent genesis events of programmable transcription factors, which we name TnpB-like nuclease-dead repressors (TldRs). These proteins use naturally occurring guide RNAs to specifically target conserved promoter regions of the genome, leading to potent gene repression in a mechanism akin to CRISPR interference technologies invented by humans7. Focusing on a TldR clade found broadly in Enterobacteriaceae, we discover that bacteriophages exploit the combined action of TldR and an adjacently encoded phage gene to alter the expression and composition of the host flagellar assembly, a transformation with the potential to impact motility8, phage susceptibility9, and host immunity10. Collectively, this work showcases the diverse molecular innovations that were enabled through repeated exaptation of transposon-encoded genes, and reveals the evolutionary trajectory of diverse RNA-guided transcription factors.

Annual indoxacarb resistance in Helicoverpa armigera(Hübner) populations collected from various crops in Australia was monitored between 2013 and 2023. Resistance frequency determined by F2screening using a predetermined discriminating dose of indoxacarb, was lowest in the 2013–2014 and 2015–2016 seasons at 0.0164 and 0.0246, respectively. Resistance then increased significantly to a ten-year high of 0.0869 in 2018–2019 but declined to 0.0557 in 2019–2020 during a severe drought, remaining relatively stable thereafter to 2023. Indoxacarb resistance was first detected in H. armigeracollected from maize in the Gwydir valley, New South Wales, in 2013 (strain GY7-39). In 2017, a second indoxacarb resistant H. armigerastrain (UN1U3-10) was isolated from a population collected in chickpeas in the Liverpool Plains, New South Wales. Indoxacarb resistance of this strain was characterized to evaluate its potential to compromise the ongoing effectiveness of insecticide resistance management strategies in Australian farming systems. Survival at the discriminating dose of indoxacarb in UN1U3-10 was 28.9, 52.6, 86.7, and 92.9% in the F2, F3, F4, and F5, respectively. Following introgression with a susceptible strain and reselection with the discriminating dose of indoxacarb, the resistance ratio of UN1U3-10 was approximately 800-fold. Resistance was autosomal, incompletely dominant and conferred by more than 1 locus. While indoxacarb resistance in UN1U3-10 did not confer to emamectin benzoate or spinetoram and there was no evidence of major cross-resistance to the Bt toxins Cry1A, Cry2A or Vip3A, there was 5-fold reduced sensitivity to chlorantraniliprole. Indoxacarb resistance was suppressed by approximately 10-fold by PBO with no synergism by TPP or DEM, suggesting the involvement of cytochrome P450 enzymes. A stability analysis indicated a fitness cost may be associated with the genes that confer resistance in the UN1U3-10 strain. The potential risk for diverse indoxacarb resistance in the Australian H. armigerapopulation is discussed.

Insertion sequences are compact and pervasive transposable elements found in bacteria, which encode only the genes necessary for their mobilization and maintenance1. IS200- and IS605-family transposons undergo ‘peel-and-paste’ transposition catalysed by a TnpA transposase2, but they also encode diverse, TnpB- and IscB-family proteins that are evolutionarily related to the CRISPR-associated effectors Cas12 and Cas9, respectively3,4. Recent studies have demonstrated that TnpB and IscB function as RNA-guided DNA endonucleases5,6, but the broader biological role of this activity has remained enigmatic. Here we show that TnpB and IscB are essential to prevent permanent transposon loss as a consequence of the TnpA transposition mechanism. We selected a family of related insertion sequences from Geobacillus stearothermophilusthat encode several TnpB and IscB orthologues, and showed that a single TnpA transposase was broadly active for transposon mobilization. The donor joints formed upon religation of transposon-flanking sequences were efficiently targeted for cleavage by RNA-guided TnpB and IscB nucleases, and co-expression of TnpB and TnpA led to substantially greater transposon retention relative to conditions in which TnpA was expressed alone. Notably, TnpA and TnpB also stimulated recombination frequencies, surpassing rates observed with TnpB alone. Collectively, this study reveals that RNA-guided DNA cleavage arose as a primal biochemical activity to bias the selfish inheritance and spread of transposable elements, which was later co-opted during the evolution of CRISPR–Cas adaptive immunity for antiviral defence.

The long‐term viability of rice production in the midsouthern United States could be affected by irrigation management strategy. This study was conducted to determine if rice sustainability can be improved through manipulation of the irrigation threshold. The effects of an alternate wetting and drying (AWD) irrigation threshold and cultivar on water applied, rice grain yield, seed quality, irrigation water use efficiency, and net returns were investigated at Stoneville, MS, on a Sharkey clay (very fine, smectitic, thermic Chromic Epiaquert) during the 2015 through 2017 growing seasons. Water applied increased exponentially from 316 mm for the AWD threshold of −40 cm to 1061 mm for the conventional flood. For both hybrid and inbred lines, rice grain yield decreased linearly at a rate of 14 kg ha−1for each centimeter decrease in irrigation threshold. Alternate wetting and drying irrigation threshold had no effect on seed quality parameters including chalk, milling total, and milling whole. Net returns were higher for AWD compared to a conventional flood for all cultivars. The economically optimal irrigation threshold was dependent on cultivar and rice price. Converting from a conventional flood to AWD will likely improve the sustainability of rice production in the midsouthern United States. Water applied increased exponentially as the irrigation threshold increased from ‐40 to 10 cm above the soil.Rice grain yield responded similarly to altering the irrigation threshold regardless of cultivar evaluated.Alternate wetting and drying was more profitable than a continuous flood regardless of cultivar evaluated.The economically optimal irrigation threshold varies according to cultivar and rice price.

IMPORTANCE: There remains an unmet need to improve clinical outcomes in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). OBJECTIVE: To evaluate clinical benefit of first-line nivolumab plus ipilimumab vs nivolumab alone in patients with R/M SCCHN. DESIGN, SETTING, AND PARTICIPANTS: The CheckMate 714, double-blind, phase 2 randomized clinical trial was conducted at 83 sites in 21 countries between October 20, 2016, and January 23, 2019. Eligible participants were aged 18 years or older and had platinum-refractory or platinum-eligible R/M SCCHN and no prior systemic therapy for R/M disease. Data were analyzed from October 20, 2016 (first patient, first visit), to March 8, 2019 (primary database lock), and April 6, 2020 (overall survival database lock). INTERVENTIONS: Patients were randomized 2:1 to receive nivolumab (3 mg/kg intravenously [IV] every 2 weeks) plus ipilimumab (1 mg/kg IV every 6 weeks) or nivolumab (3 mg/kg IV every 2 weeks) plus placebo for up to 2 years or until disease progression, unacceptable toxic effects, or consent withdrawal. MAIN OUTCOMES AND MEASURES: The primary end points were objective response rate (ORR) and duration of response between treatment arms by blinded independent central review in the population with platinum-refractory R/M SCCHN. Exploratory end points included safety. RESULTS: Of 425 included patients, 241 (56.7%; median age, 59 [range, 24-82] years; 194 males [80.5%]) had platinum-refractory disease (nivolumab plus ipilimumab, n = 159; nivolumab, n = 82) and 184 (43.3%; median age, 62 [range, 33-88] years; 152 males [82.6%]) had platinum-eligible disease (nivolumab plus ipilimumab, n = 123; nivolumab, n = 61). At primary database lock, the ORR in the population with platinum-refractory disease was 13.2% (95% CI, 8.4%-19.5%) with nivolumab plus ipilimumab vs 18.3% (95% CI, 10.6%-28.4%) with nivolumab (odds ratio [OR], 0.68; 95.5% CI, 0.33-1.43; P = .29). Median duration of response for nivolumab plus ipilimumab was not reached (NR) (95% CI, 11.0 months to NR) vs 11.1 months (95% CI, 4.1 months to NR) for nivolumab. In the population with platinum-eligible disease, the ORR was 20.3% (95% CI, 13.6%-28.5%) with nivolumab plus ipilimumab vs 29.5% (95% CI, 18.5%-42.6%) with nivolumab. The rates of grade 3 or 4 treatment-related adverse events with nivolumab plus ipilimumab vs nivolumab were 15.8% (25 of 158) vs 14.6% (12 of 82) in the population with platinum-refractory disease and 24.6% (30 of 122) vs 13.1% (8 of 61) in the population with platinum-eligible disease. CONCLUSIONS AND RELEVANCE: The CheckMate 714 randomized clinical trial did not meet its primary end point of ORR benefit with first-line nivolumab plus ipilimumab vs nivolumab alone in platinum-refractory R/M SCCHN. Nivolumab plus ipilimumab was associated with an acceptable safety profile. Research to identify patient subpopulations in R/M SCCHN that would benefit from nivolumab plus ipilimumab over nivolumab monotherapy is warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02823574

Whether the human fetus and the prenatal intrauterine environment (amniotic fluid and placenta) are stably colonized by microbial communities in a healthy pregnancy remains a subject of debate. Here we evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbial ecology, bioinformatics, immunology, clinical microbiology and gnotobiology, and assess possible mechanisms by which the fetus might interact with microorganisms. Our analysis indicates that the detected microbial signals are likely the result of contamination during the clinical procedures to obtain fetal samples or during DNA extraction and DNA sequencing. Furthermore, the existence of live and replicating microbial populations in healthy fetal tissues is not compatible with fundamental concepts of immunology, clinical microbiology and the derivation of germ-free mammals. These conclusions are important to our understanding of human immune development and illustrate common pitfalls in the microbial analyses of many other low-biomass environments. The pursuit of a fetal microbiome serves as a cautionary example of the challenges of sequence-based microbiome studies when biomass is low or absent, and emphasizes the need for a trans-disciplinary approach that goes beyond contamination controls by also incorporating biological, ecological and mechanistic concepts.

I. Introduction 436 II. Recent Developments in Fidelity Bond Litigation: "Direct Means Direct" 436 III. Recent Developments in CGL Coverage Litigation: Determining the Trigger of Coverage in Long-Latency Bodily Injury [...]

To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1540-5850.2010.00968.x Byline: SKIP KRUEGER (1), ROBERT W. WALKER (2) Abstract: One of the central claims of public administration is that management matters for the performance of public entities. Quantifying the impact of organizational management is thus central to the empirical evaluation of this claim. Utilizing novel features of the Government Performance Project (GPP), we assess the impact of state-level management practices on the credit quality of US states. The central challenge-that both the GPP data and bond ratings take the form of ordinal grades-suggests a common solution utilizing multiple indicators of a latent construct (management capacity and credit quality) with appropriate measurement models. After describing the characteristics of the measurement approach, we derive management capacity scores from the GPP data and credit quality scores using bond ratings from the three rating agencies. These derived scores then allow us to test linkages between credit quality of the US states and broad aspects of their relative management capacity. On the whole, we show that financial management capacity influences credit quality, while the evidence is less clear that other forms of management capacity matter. Author Affiliation: (1)Department of Public Administration, University of North Texas, 1155 Union Circle #310617, Denton, TX 76203-5017, USA (2)Department of Political Science, Center for Applied Statistics, Washington University in St. Louis, St. Louis, MO 63130-4899, USA

Background: Recently, a genetic variant (rs738409; C [right arrow] G) of the PNPLA3 gene was identified to be associated with increased hepatic fat deposition, and the effect was more pronounced in Hispanics. Animal models have also shown that PNPLA3 expression can be regulated by dietary carbohydrate. Objective: The aim of this study was to examine whether the influence of PNPLA3 genotype on hepatic fat is modulated by dietary factors in Hispanic children. Design: PNPLA3 was genotyped in 153 Hispanic children (75% female, ages 8-18 y) by using the TaqMan method. Dietary intake was assessed by using three 24-h dietary recalls or diet records. Visceral adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAAT), and hepatic fat fraction (HFF) were assessed in multiple abdominal slices by magnetic resonance imaging. Analysis of covariance was used to assess the diet x genotype interaction in liver fat, with the following a priori covariates: sex, age, energy, VAT, and SAAT. Results: HFF was influenced by a significant interaction between genotype and diet (genotype x carbohydrate, P = 0.04; genotype x total sugar, P = 0.01). HFF was positively related to carbohydrate (r = 0.31, P = 0.04) and total sugar (r = 0.34, P = 0.02) intakes but only in the GG group, independent of covariates. Dietary variables were not related to HFF in the CC or CG group or to other fat depots in all genotype groups. Conclusions: These findings suggest that Hispanic children carrying the GG genotype are susceptible to increased hepatic fat when dietary carbohydrate intake, specifically sugar, is high. Specific dietary interventions based on genetic predisposition in this population may lead to more effective therapeutic outcomes for fatty liver. This trial was registered at clinicaltrials.gov as NCT00697580, 1951642394A1, and NCT00693511. Am J Clin Nutr 2010;92:1522-7. doi: 10.3945/ajcn.2010.30185.

I. Excess Insurance 330 A. Regulatory Developments 330 B. Case Law Developments 330 1. Exhaustion 331 2. Excess Insurer Duties 335 3. Excess Insurer Rights 339 4. Priority of Coverage [...]

INTRODUCTION The 1999 Institute of Medicine report entitled To Err Is Human (1) highlighted the diagnostic and cognitive aspects of medical error, and emphasized the role of simulation in procedural [...], Objective: Residents must become proficient in a variety of procedures. The practice of learning procedural skills on patients has come under ethical scrutiny, giving rise to the concept of simulation-based medical education. Resident training in a simulated environment allows skill acquisition without compromising patient safety. We assessed the impact of a simulation-based procedural skills training course on residents' competence in the performance of critical resuscitation procedures. Methods: We solicited self-assessments of the knowledge and clinical skills required to perform resuscitation procedures from a cross-sectional multidisciplinary sample of 28 resident study participants. Participants were then exposed to an intensive 8-hour simulation-based training program, and asked to repeat the self-assessment questionnaires on completion of the course, and again 3 months later. We assessed the validity of the self-assessment questionnaire by evaluating participants' skills acquisition through an Objective Structured Clinical Examination station. Results: We found statistically significant improvements in participants' ratings of both knowledge and clinical skills during the 3 self-assessment periods (p < 0.001). The participants' year of postgraduate training influenced their self-assessment of knowledge ([F.sub.2,25] = 4.91, p < 0.01) and clinical skills ([F.sub.2,25] = 10.89, p < 0.001). At the 3-month follow-up, junior-level residents showed consistent improvement from their baseline scores, but had regressed from their posttraining measures. Senior-level residents continued to show further increases in their assessments of both clinical skills and knowledge beyond the simulation-based training course. Conclusion: Significant improvement in self-assessed theoretical knowledge and procedural skill competence for residents can be achieved through participation in a simulation-based resuscitation course. Gains in perceived competence appear to be stable over time, with senior learners gaining further confidence at the 3-month follow-up. Our findings support the benefits of simulation-based training for residents. Keywords: emergency medicine, resident, education, simulation, procedures, critical care RESUME Objectif : Les residents doivent acquerir des competences dans une variete de techniques d'interventions. La pratique de l'apprentissage de techniques d'interventions sur des patients a fait l'objet de critiques sur le plan ethique, ce qui a donne naissance a la notion de formation medicale par simulation. La formation des residents dans un environnement simule permet d'acquerir des competences sans compromettre la securite des patients. Nous avons evalue l'incidence d'un cours de formation par simulation a des techniques d'interventions sur les competences des residents dans l'execution d'interventions de reanimation. Methodes : Nous avons demande a un echantillon multidisciplinaire et transversal de 28 residents d'auto-evaluer leurs connaissances et competences cliniques relatives a des interventions de reanimation. Les participants ont ensuite pris part a un programme intensif de formation par simulation d'une duree de 8 heures. Nous leur avons ensuite demande de refaire l'auto-evaluation a la fin du cours, puis 3 mois plus tard. Nous avons determine la validite du questionnaire d'auto-evaluation en evaluant l'acquisition de leurs competences par le biais d'un examen clinique objectif structure. Resultats : Nous avons constate des ameliorations statistiquement significatives en ce qui a trait aux notes accordees par les participants sur les connaissances et les competences cliniques pour les 3 periodes d'auto-evaluation (p < 0,001). L'annee de formation des participants a influence l'auto-evaluation de leurs connaissances ([F.sup.2,25] = 4,91, p < 0,01) et de leurs competences cliniques ([F.sub.2,25] = 10,89, p < 0,001). Lors du suivi de 3 mois, les residents junior ont montre une amelioration constante par rapport a la note de base, mais ont indique une baisse par rapport a l'evaluation post-formation. Les residents senior ont continue d'evaluer a la hausse leurs connaissances et leurs competences cliniques apres avoir suivi la formation par simulation. Conclusion : La participation a un cours par simulation sur les interventions de reanimation peut permettre aux residents d'ameliorer de facon significative les connaissances theoriques et les competences procedurales auto-evaluees. Les gains de competences percues semblent etre stables dans le temps, les residents senior etant plus confiants lors du suivi de 3 mois. Nos constatations corroborent le fait que la formation par simulation comporte des avantages pour les residents.

To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1540-5850.2009.00925.x Byline: ROBERT W. WALKER (1), SKIP KRUEGER (2) Abstract: Bond ratings on state-issued debt provide a signal to credit markets that help them charge an appropriate interest rate, based on the risk of payment default. Though actual default may occur only in extreme circumstances, observed differences in ratings and interest costs across states and time demonstrate that a sound economy, strong financials, and stable policies matter. When data on the factors that presumably affect ratings is public and easily accessible, making sense of differences of opinion between bond rating agencies is difficult. We suggest that such differences-observed as so-called split bond ratings-are often ephemeral. Utilizing a simulation method to uncover the latent credit risk presented by each state, we show that split ratings on state bonds are often due to the fact that presumed category overlap between rating agencies is absent when evaluated on a common latent scale. Most observed state bond rating splits from 1997 through 2006 can be explained by this category mismatch. Our approach has broad implications for pricing state debt, as well as pricing rated debt in other capital market sectors. Author Affiliation: (1)Department of Political Science, Center for Applied Statistics, Washington University in St. Louis, St. Louis, MO 63130-4899 (2)Department of Public Administration, University of North Texas, 1155 Union Circle #310617, Denton, Texas 76203-5017

People with Parkinson’s disease (PD) have higher rates of hospitalisation and healthcare utilisation compared to the general population. The COVID-19 pandemic caused significant changes in admissions to hospital and access to healthcare. People with PD are some of the most vulnerable to such changes. There is no pre-existing data on the cause and duration of admission to hospital of people with PD during the COVID-19 pandemic. To determine the cause, duration, and outcome of hospital admissions to Northumbria Healthcare NHS Foundation Trust (NHCFT) for people with idiopathic Parkinson’s disease (IPD) in 2020. All people with IPD who had an emergency admission to NHCFT between 01/01/2020 and 31/12/2020 were identified. Demographic and disease characteristics, the number, duration, cause of admission and the location prior to admission were collected from an audit of medical notes. 271 people with IPD had one or more emergency admissions to NHCFT between 01/01/2020 and 31/12/2020. There was a total of 453 emergency admissions, with a median duration of 5 (IQR 2-13) days. The most common causes of admission to hospital were PD-related motor dysfunction (includes falls with no other underlying cause or associated injury) and injury (includes falls with fracture), at 78 (17.2%) and 70 (15.5%) respectively. People with IPD had a short duration but high number of emergency admissions to hospital. Our chronological data on number of admissions shows a peak in admissions during August 2020. As a result of these findings and emerging data we suggest that individuals with PD deconditioned during 2020.

State bond ratings from 1995 through 2000 are analyzed to study the claim that state debt ratings becomes lower due to political turnover and a divided government since these are factors that rating agencies consider. This is important since credit markets face the risk of future policy changes when considering the purchase of state debt.

The study determines whether placental-derived kynurenines contributes to infection-mediated fetal cerebral injury. Inflammatory mediated release of kynurenines from placentae exposes the fetus to significant amounts of potentially neurotoxic substances.

The Homeland Security Department's Border and Transportation Security Directorate, in a way, is the Homeland Security Department. For starters, it's the largest of the department's five directorates, covering road, rail […]

Superlative executive talent planning has become a very necessary, yet very volatile, element of corporate success. The board's duty to ensure sound CEO succession has grown more crucial, and is [...]

Mirroring the drive to transform government, the federal IT work force is undergoing its own transformation. "In a sense, its part of a trend from blue collar to white collar--going […]

These are the times that try the souls of government security managers. The threat of cyberattacks on government systems is escalating as computers become ever more interconnected, use of the […]

The landscape of government IT services acquisition is shifting. Sure, agencies are buying more IT services. But the bigger story is that they are buying them differently. And they are […]

Taming the compliance monster begins at the top, but it doesn't end there. Management must build momentum and sustain it at all levels of an agency. 'To a great extent, […]

A placental abnormality can cause increases in kynurenic acid and quinolinic acid in the blood of the fetus, according to a study in sheep. Quinolinic acid can damage the brain, whereas kynurenic acid is believed to protect the brain.

The level of quinolinic acid increases in the brains of fetuses who have been exposed to low levels of oxygen and a reduced blood supply, according to a study in sheep. Quinolinic acid is toxic to nerve cells when present in excessive amounts.

We consider the generalized Ericksen model of liquid crystals, which is an energy with 8 independent “elastic”constants that depends on two order parameters n (director) and s(variable degree of orientation). In addition, we present a new finite element discretization for this energy, that can handle the degenerate elliptic part without regularization, with the following properties: it is stable and it Γ-converges to the continuous energy. Moreover, it does not require the mesh to be weakly acute (which was an important assumption in our previous work). Furthermore, we include other effects such as weak anchoring (normal and tangential), as well as fully coupled electro-statics with flexo-electric and order-electric effects. We also present several simulations (in 2-D and 3-D) illustrating the effects of the different elastic constants and electric field parameters.

The fetus appears to have a greater capacity to produce kynurenine from tryptophan than its mother, according to a study in sheep. Kynurenine is believed to protect the brain from damage caused by low oxygen levels.

Nitric oxide appears to cause blood vessels in the uterus to relax. This relaxation of blood vessels is called vasodilation and chemicals and drugs that cause it are called vasodilators. Researchers analyzed the effect of nitric oxide in the uterus by infusing a chemical that inhibits nitric oxide production into the uterine arteries of sheep. The nitric oxide inhibitor caused uterine blood flow to decrease and increased arterial blood pressure. This confirms that nitric oxide acts as a vasodilator during pregnancy.

Introduction: Tessier 30 facial cleft is a rare anomaly presenting in the soft and hard tissues over the central lower face. Owing to the rarity of cases and difficulty of treatment, there is no universally accepted surgical management strategy. The last comprehensive literature review of Tessier 30 clefts was in 1996. This report aims to update the literature to inform decision-making on treating Tessier 30 cases.Methodology: A literature search was performed. PubMed, SCOPUS, and OVID databases were searched. A total of 72 cases in 51 articles were analyzed, looking at demographics, extent of cleft, parent health, family history, procedures, follow-up, existence of other anomalies, and stages of repair.Results: Surgeons are increasingly choosing to repair Tessier 30 defects in one rather than multiple stages. Of the 72 cases studied, only 31 had documented the completed repair of the cleft. All completed soft tissue only defects were repaired in 1 stage of repair (n = 11). Where both soft tissue and mandible was involved (n = 20), 55% (n = 11) had undergone 1-stage repair to address the Tessier 30 cleft.Discussion: We argue that a single-stage approach is preferable to multistage. Primary mucogingivoperiosteoplasty should be undertaken in children at the time of management of the soft tissue cleft. The timing of this procedure should be in the latter half of the first year of life, as this is when mandibular symphyseal fusion normally occurs. We have suggested a treatment protocol and we hope that future case reports use our minimum data set.