Apparent Reversal Research Articles

Aripiprazole prevents stress-induced anxiety and social impairment, but impairs antipredatory behavior in zebrafish

Environmental pollution caused by antipsychotic residues is a relevant ecological problem. Studies revealed that residues of these drugs are present in a wide range of different ecosystems and can have adverse effects on non-target organisms even in low environmental concentrations. Among these antipsychotic drugs, aripiprazole (APPZ) is a second-generation atypical antipsychotic that is a partial agonist of dopaminergic and serotoninergic receptors. APPZ is used to treat schizophrenia, bipolar disorder, autism, obsessive-compulsive disorder, and anxiety or panic disorders. Thus, in this study we posed the following question: “What will be the behavioral effects of waterborne APPZ on fish?” To answer this question, we exposed adult zebrafish to different APPZ concentrations (0.556, 5.56, and 556 ng/L) for 15 min and evaluated their exploratory, anxiety-like, social, and anti-predatory behaviors. Our results showed that, despite the apparent beneficial reversal of stress-induced social impairment and anxiety-like behavior, APPZ exposure impaired the anti-predatory reaction of adult zebrafish. Taken altogether, our results show that APPZ-exposed zebrafish may have a decreased perception of predators, even at concentrations lower than those already detected in the environment. A failure to exhibit an antipredatory response may favor the predator, decrease the fitness of the prey species, and, consequently, affect the food chain. Our results highlight the risks and consequences associated with APPZ residues in water, which may affect aquatic life and endanger species that depend on appropriate behavioral responses for survival.

Caveolin-1 Y14 phosphorylation suppresses tumor growth while promoting invasion.

Caveolin-1 is a transmembrane protein with both tumor promoter and suppressor functions that remain poorly understood. Cav1 phosphorylation by Src kinase on tyrosine 14 is closely associated with focal adhesion dynamics and tumor cell migration, however the role of pCav1 in vivo in tumor progression remains poorly characterized. Herein, we expressed phosphomimetic Y14D, wild type, and non-phosphorylatable Y14F forms of Cav1 in MDA-MB-435 cancer cells. Expression of Cav1Y14D reduced cell proliferation and induced the TP53 tumor suppressor. Ectopic expression in MDA-MB-435 cells of Y14 phosphorylatable Cav1 was required for induction of TP53 in response to oxidative stress. Cav1Y14D promotes an apparent reversal of the Warburg effect and markedly inhibited tumor growth in vivo. However, Cav1 induced pseudopodial recruitment of glycolytic enzymes, and time-lapse intravital imaging showed increased invadopodia protrusion and extravasation into blood vessels for Cav1WT and Y14D but not for Y14F. Our results suggest that Cav1 Y14 phosphorylation levels play a role in the conflicting demands on metabolic resources associated with cancer cell proliferation versus motility.

Engineered oncolytic virus for the treatment of cholesteatoma: A pilot in vivo study.

ObjectiveDetermine if oncolytic herpes simplex virus (oHSV) can eradicate cholesteatoma (CHST) in a gerbil model.MethodsAn in vivo model of CHST was developed in Mongolian gerbils by combining Pseudomonas aeruginosa inoculation with double ligation of the external auditory canal (EAC). CHST size and bone thickness were measured using morphometric and volumetric quantification techniques via micro‐computed tomography (micro‐CT). The CHST induction and quantification techniques were then used in an additional group of 10 gerbils (n = 20 ears) to determine the within‐group treatment efficacy of oHSV against CHST in vivo. Treated animals received either one, two, or three intrabullar injections of oHSV between 2 and 6 weeks postinduction of CHST.ResultsThe P. aeruginosa inoculation plus double EAC ligation technique successfully induced a range of CHST growth in 100% of the ears in the model‐development group. Osteolytic effects of CHST were observed in 6% of ears whereas osteoblastic effects were observed in 31% of ears. CHST volume decreased by 50% or more in 12 of the 20 ears in the oHSV‐treatment groups. An apparent reversal of osteoblastic effects was also observed in three out of four ears 6 weeks following the third oHSV injection.Conclusions P. aeruginosa inoculation plus double EAC ligation reliably induces CHST formation in gerbil. CT‐based volumetric measures are significantly more accurate than single‐slice morphometric area measures for quantification of CHST size. Treatment with oHSV appears to be efficacious for reducing CHST volume by as much as 77% with as few as one treatment.Level of EvidenceNA

In Epigenomic Studies, Including Cell-Type Adjustments in Regression Models Can Introduce Multicollinearity, Resulting in Apparent Reversal of Direction of Association.

Background: Association studies of epigenome-wide DNA methylation and disease can inform biological mechanisms. DNA methylation is often measured in peripheral blood, with heterogeneous cell types with different methylation profiles. Influences such as adiposity-associated inflammation can change cell-type proportions, altering measured blood methylation levels. To determine whether associations between loci-specific methylation and outcomes result from cellular heterogeneity, many studies adjust for estimated blood cell proportions, but high correlations between methylation and cell-type proportions could violate the statistical assumption of no multicollinearity. We examined these assumptions in a population-based study.Methods: CDKN2A promoter CpG methylation was measured in peripheral blood from 812 adolescents aged 17 years (Western Australian Pregnancy Cohort Study). Loge adolescent BMI was used as the outcome in a regression analysis with DNA methylation as predictor, adjusting for age/sex. Further regression analyses additionally adjusted for estimated cell-type proportions using the reference-based Houseman method, and simulations modeled the effects of varying levels of correlation between cell proportions and methylation. Correlations between estimated cell proportions and CpG methylation from Illumina 450K were measured.Results: Lower DNA methylation was associated with higher BMI when cell-type adjustment was not included; for CpG4, β = −0.004 logeBMI/%methylation (95% CI −0.0065, −0.001; p = 0.003). The direction of association reversed when adjustment for six cell types was made; for CpG4, β = 0.004 logeBMI/%methylation (−0.0002, 0.0089; p = 0.06). Correlations between CpG methylation and cell-type proportions were high, and variance inflation factors (VIFs) were extremely high (25 to 113.7). Granulocyte count was correlated with BMI, and removing granulocytes from the regression model reduced all VIFs to <3.1, with persistence of a positive association between methylation and BMI [CpG4 β = 0.004 logeBMI/%methylation (−0.0002, 0.0088; p = 0.06)]. Simulations supported major effects of multicollinearity on regression results.Conclusions: Where cell types are highly correlated with other covariates in regression models, the statistical assumption of no multicollinearity may be violated. This can result in reversal of direction of association, particularly when examining associations with phenotypes related to inflammation, as CpG methylation may associate with changes in cell-type proportions. Removing predictors with high correlations from regression models may remove the multicollinearity. However, this might hinder biological interpretability.

A Growing Social Divide in Body Mass Index, Strength, and Fitness of Swedish Male Conscripts

PurposeThe aim of the study was to monitor trends in socioeconomic inequalities in body mass index (BMI), cardiorespiratory fitness (CRF), and muscular strength over several decades in a population of Swedish males aged 18–19 years. MethodsThe cohort consists of 1.5 million young men attending military conscript examinations from late 1968 to 2005. Parental education was used as a marker for socioeconomic conditions in the conscripts' families of origin. Changing gradient in BMI, CRF, and muscular strength in sons of parents with higher and lower educational attainment was evaluated during four periods covering 36 years. ResultsOver the course of the obesity epidemic, BMI remained higher in conscripts with lesser (vs. higher) parental education. Moreover, the absolute difference in obesity prevalence between groups showed a continuous increase, from .6% to 3.9%, indicating growing inequalities. Regarding fitness, lower CRF was consistently associated with less parental education, but with no clear secular trend in the magnitude of the difference. Finally, social differences in muscular strength changed in direction, from lower strength among conscripts with higher parental education in the initial observation period to lower strength associated with lower parental education in the final decade studied. ConclusionsAmong Swedish conscripts entering adulthood, social gradients in BMI and obesity widened continuously between 1968 and 2005. An apparent reversal of the earlier gradient in muscular strength in young men may be related to societal trends in occupational and leisure-time physical activity over the observation period. This cohort is being continually monitored through national registries for obesity-related comorbidities in later life.

Standing up to the canoe: Competing cognitive biases in the encoding of stative spatial relations in a language with a single spatial preposition

AbstractThis paper discusses how verbal directional markers are used to encode stative spatial relations in the Oceanic language Äiwoo. It argues that the apparent reversal of directional meaning in stative expressions, where ‘up’ is used in expressions meaning ‘underneath’, ‘down’ in expressions meaning ‘above’, and ‘out’ in expressions meaning ‘inside’, can be explained by a fictive motion analysis where the figure is construed as metaphorically moving towards the ground. It moreover argues that in expressions where motion leads to a resulting spatial configuration, where ‘up’ means ‘on top of’ rather than ‘underneath’, this reading is overridden by the so-called goal bias, whereby the resultant configuration is more cognitively salient than the motion producing it. It suggests that the linguistic construal of stative spatial relations may to some extent be correlated with the formal means of expression, where marking by adpositions favours a ‘search domain’ construal whereas encoding within the verb favours a ‘fictive path’ construal. It thus provides a new angle on the linguistic encoding of spatial relations, an area which has been subject to much research within cognitive linguistics, but which so far has paid little attention to the possibility of encoding stative spatial relations within the verb.

Geological and Geochemical Characteristics and Exploration Prospect of Coal‐Derived Tight Sandstone Gas in China: Case Study of the Ordos, Sichuan, and Tarim Basins

AbstractThis work extensively investigated global tight sandstone gas, and geologically and geochemically analyzed the tight sandstone gas in China's Ordos, Sichuan, and Tarim basins. We compared typical tight sandstone gas in China with that in North America. We proposed six conditions for the formation of China's tight sandstone gas, and illustrated the geological characteristics of tight sandstone gas. In China, gas‐bearing tight sandstones were mainly deposited in continental lake deltas and marine‐terrigenous facies basin environments, associated with coal‐measure strata, and were mostly buried deeper than 2000 m under a formation pressure of 20–30 MPa, with pressure coefficients varying from overpressure to negative pressure. In other countries, tight gas bearing sandstones were dominantly deposited in marine to marine‐terrigenous facies environments, occurred in coal‐measure strata, and were mostly buried shallower than 2000 m in low‐pressure systems. We systematically analyzed tight sandstone gas in the Ordos, Sichuan, and Tarim basins in terms of chemical compositions, geochemical characteristics of carbon isotopes, origins, and sources. Tight sandstone gas in China usually has a hydrocarbon content of &gt;95%, with CH41 content &gt;90%, and a generally higher dry coefficient. In the three above‐mentioned large tight sandstone gas regions, δ13C1 and δ13C2 mainly ranges from –42‰ to –28‰ and from –28‰ to –21‰, respectively. Type III coal‐measure source rocks that closely coexist with tight reservoirs are developed extensively in these gas regions. The organic petrology of source rocks and the carbon isotope compositions of gas indicate that tight sandstone gas in China is dominantly coal‐derived gas generated by coal‐measure strata. Our analysis of carbon isotope series shows that local isotope reversals are mainly caused by the mixing of gases of different maturities and that were generated at different stages. With increasing maturity, the reversal tendency becomes more apparent. Moreover, natural gas with medium‐low maturity (e.g., Xujiahe Formation natural gas in the Sichuan Basin) presents an apparent reversal at a low‐maturity stage, a normal series at a medium ‐maturity stage, and a reversal tendency again at a high‐maturity stage. Finally, we proposed four conditions for preferred tight sandstone gas “sweep spots,” and illustrated the recoverable reserves, proven reserves, production, and exploration prospects of tight sandstone gas. The geological and geochemical characteristics, origins, sources, and exploration potential of tight sandstone gas in China from our research will be instructive for the future evaluation, prediction, and exploration of tight sandstone gas in China and abroad.

Moral Conscience through the Ages

Moral Conscience through the Ages

Inactivation of Cancer-Associated-Fibroblasts Disrupts Oncogenic Signaling in Pancreatic Cancer Cells and Promotes Its Regression.

Resident fibroblasts that contact tumor epithelial cells (TEC) can become irreversibly activated as cancer-associated-fibroblasts (CAF) that stimulate oncogenic signaling in TEC. In this study, we evaluated the cross-talk between CAF and TEC isolated from tumors generated in a mouse model of KRAS/mut p53-induced pancreatic cancer (KPC mice). Transcriptomic profiling conducted after treatment with the anticancer compound Minnelide revealed deregulation of the TGFβ signaling pathway in CAF, resulting in an apparent reversal of their activated state to a quiescent, nonproliferative state. TEC exposed to media conditioned by drug-treated CAFs exhibited a decrease in oncogenic signaling, as manifested by downregulation of the transcription factor Sp1. This inhibition was rescued by treating TEC with TGFβ. Given promising early clinical studies with Minnelide, our findings suggest that approaches to inactivate CAF and prevent tumor-stroma cross-talk may offer a viable strategy to treat pancreatic cancer.Significance: In an established mouse model of pancreatic cancer, administration of the promising experimental drug Minnelide was found to actively deplete reactive stromal fibroblasts and to trigger tumor regression, with implications for stromal-based strategies to attack this disease. Cancer Res; 78(5); 1321-33. ©2018 AACR.

Neurotoxic chemicals in adipose tissue: A role in puzzling findings on obesity and dementia.

Midlife obesity is associated with increased risk of dementia, whereas late-life obesity is commonly associated with a lower risk of dementia. Although methodologic issues are often discussed in this apparent risk reversal, chronic exposure to low-dose organochlorine pesticides (OCPs), an emerging risk factor for dementia in general populations, may contribute to a direct explanation for these differences. OCPs are strong lipophilic chemicals with very long half-lives (several years), primarily stored in adipose tissue and very slowly released and metabolized over years. As serum concentrations of neurotoxic OCPs strongly correlate with brain OCPs (r = 0.95), any condition enhancing the release of OCPs from the adipose tissue into circulation would increase the risk of dementia. Increased release of OCPs from adipose tissue typically occurs in (1) dysfunctional adipocytes accompanied by uncontrolled lipolysis and (2) weight loss. Weight gain may help sequester circulating OCPs in adipose tissue. As obesity is the most common reason that adipocytes become dysfunctional, midlife obesity can increase dementia risk through the chronic release of OCPs into circulation. However, late-life obesity potentially decreases dementia risk because weight loss after midlife will increase the release of OCPs while weight gain may actually decrease the release. These countervailing forces may underlie paradoxical associations with dementia of obesity in midlife vs late life which is influenced by weight change after midlife. This hypothesis should be tested in future experimental and human studies on obesity and dementia.

A multicenter, randomized study of decitabine as epigenetic priming with induction chemotherapy in children with AML

BackgroundDecitabine is a deoxycytidine nucleoside derivative inhibitor of DNA-methyltransferases, which has been studied extensively and is approved for myelodysplastic syndrome in adults but with less focus in children. Accordingly, we conducted a phase 1 multicenter, randomized, open-label study to evaluate decitabine pre-treatment before standard induction therapy in children with newly diagnosed AML to assess safety and tolerability and explore a number of biologic endpoints.ResultsTwenty-four patients were fully assessable for all study objectives per protocol (10 in Arm A = epigenetic priming induction, 14 in Arm B = standard induction). All patients experienced neutropenia and thrombocytopenia. The most common grade 3 and 4 non-hematologic adverse events observed were gastrointestinal toxicities and hypophosphatemia. Plasma decitabine PK were similar to previously reported adult data. Overall CR/CRi was similar for the two arms. MRD negativity at end-induction was 85% in Arm A versus 67% in Arm B patients. DNA methylation measured in peripheral blood over the course of treatment tracked with blast clearance and matched marrow aspirates at day 0 and day 21. Unlike end-induction marrow analyses, promoter methylation in blood identified an apparent reversal of response in the lone treatment failure, 1 week prior to the patient’s marrow aspirate confirming non-response. Decitabine-induced effects on end-induction (day 35–43 following initiation of treatment) marrows in Arm A were reflected by changes in DNA methylation in matched paired marrow diagnostic aspirates.ConclusionsThis first-in-pediatrics trial demonstrates that decitabine prior to standard combination chemotherapy is feasible and well tolerated in children with newly diagnosed AML. Pre-treatment with decitabine may represent a newer therapeutic option for pediatric AML, especially as it appears to induce important epigenetic alterations. The novel biological correlates studied in this trial offer a clinically relevant window into disease progression and remission. Additional studies are needed to definitively assess whether decitabine can enhance durability responses in children with AML.Trial registrationNCT01177540

Sediment sequences and palynology of outer South Bay, Manitoulin Island, Ontario: Connections to Lake Huron paleohydrologic phases and upstream Lake Agassiz events

South Bay on the southern coast of Manitoulin Island is a fjord-like embayment connected to Lake Huron by a natural narrow gap in the bay's outer sill 6.5–14 m above the lake. A seismic profile, pollen, plant macrofossil, grain size analyses, and other sediment properties of two piston cores from a shallow outer basin of the bay document a 9 m-thick sediment section comprising rhythmically laminated clay under silty clay containing zones with small molluscan shells and marsh detritus. A sandy pebbly layer under soft silty clay mud overlies these sediments. This stratigraphy represents inundation by deep glacial Lake Algonquin followed by the shallowing Post Algonquin series of lakes, and exposure in the early Holocene by 5 Lake Stanley lowstands in the Lake Huron basin separated by 4 Lake Mattawa highstands. Overflow from South Bay in the first lowstand is thought to have eroded the outer sill gap. Marsh environments are inferred to have formed in the bay during subsequent lowstands. The Lake Mattawa highstands are attributed to outburst floods mainly from glacial Lake Agassiz. Palynological evidence of increased spruce occurrence, an apparent regional climate reversal, during the dry pine period is attributed to cold northwest winds from the Lake Superior basin and a lake effect from the Mattawa highstands in the Lake Huron basin. Lake waters transgressed South Bay following the pine period to form the Nipissing shore on Manitoulin Island. Transfer of Lake Huron basin drainage to southern outlets and continued glacioisostatic uplift of the region led to the present configuration of South Bay and Lake Huron.

Patterns of Emotional Availability between Mothers and Young Children: Associations with Risk Factors for Borderline Personality Disorder.

Emotional availability (EA) characterizes a warm, close relationship between caregiver and child. We compared patterns (clusters) of EA on risk factors, including those for borderline personality disorder (BPD). We sampled 70 children aged 4 to 7 years from low-socioeconomic backgrounds, 51% of whose mothers had BPD. We coded filmed interactions for EA: mothers' sensitivity, structuring, non-intrusiveness, non-hostility, and children's responsiveness to, and involvement of, mothers. We additionally coded children's over-responsiveness and over-involvement. Using person-centered analyses, we identified four clusters: high-functioning, low-functioning, asynchronous (mothers above average on two of four dimensions, children below) and below average. Mothers in the low-functioning cluster had lower income, less social support, more of the borderline feature of negative relationships and more depression than did mothers in the high-functioning cluster. The children in the low-functioning group had more risk factors for BPD (physical abuse, neglect, and separation from, or loss of caregivers, and negative narrative representations of the mother-child relationship in their stories) than did children in the high-functioning group. The asynchronous group included older girls who were over-responsive and over-involving with their mothers in an apparent role reversal. Interventions targeting emotional availability may provide a buffer for children facing cumulative risks and help prevent psychopathology.

Apparent Affinity Estimates and Reversal of the Effects of Synthetic Cannabinoids AM-2201, CP-47,497, JWH-122, and JWH-250 by Rimonabant in Rhesus Monkeys.

Synthetic cannabinoids have been prohibited due to abuse liability and toxicity. Four such synthetic cannabinoids, AM-2201 ([1-(5-fluoropentyl)indol-3-yl]-naphthalen-1-ylmethanone), CP-47,497 (2-[(1R,3S)-3-hydroxycyclohexyl]-5-(2-methyloctan-2-yl)phenol), JWH-122 [(4-methylnaphthalen-1-yl)-(1-pentylindol-3-yl)methanone], and JWH-250 [2-(2-methoxyphenyl)-1-(1-pentylindol-3-yl)ethanone], were tested for their capacity to produce CB1 receptor-mediated discriminative stimulus effects in two groups of rhesus monkeys. One group (n = 4) discriminated Δ9-tetrahydrocannabinol (∆9-THC; 0.1 mg/kg i.v.), and a second group (n = 4) discriminated the cannabinoid antagonist rimonabant (1 mg/kg i.v.) while receiving 1 mg/kg/12 hours of ∆9-THC. AM-2201, JWH-122, CP-47,497, JWH-250, and ∆9-THC increased ∆9-THC lever responding. Duration of action was 1-2 hours for AM-2201, JWH-122, and JWH-250 and 4-5 hours for CP-47,497 and ∆9-THC. Rimonabant (1 mg/kg) surmountably antagonized the discriminative stimulus effects of all cannabinoid agonists; the magnitude of rightward shift was 10.6-fold for AM-2201, 10.7-fold for JWH-122, 11.0-fold for CP-47,497, and 15.7-fold for JWH-250. The respective pKB values were not significantly different: 6.61, 6.65, 6.66, and 6.83. In ∆9-THC-treated monkeys discriminating rimonabant, AM-2201 (0.1 and 0.32 mg/kg), JWH-122 (0.32 and 1 mg/kg), JWH-250 (1 and 3.2 mg/kg), and CP-47,497 (0.32, 1, and 3.2 mg/kg) produced not only rate-decreasing effects that were reversed by rimonabant, but also dose-dependent, rightward shifts in the rimonabant discrimination dose-effect function. These results show striking similarity in the CB1 receptor mechanism mediating the subjective effects of AM-2201, JWH-122, JWH-250, and CP-47,497. For products containing AM-2201 and JWH-122, a short duration of action could lead to more frequent use; moreover, inattention to differences in potency among synthetic cannabinoids could underlie unexpected toxicity. Rapid reversal of effects by intravenous rimonabant has potential value in emergency situations.

When complex neuronal structures may not matter.

Much work has explored animal-to-animal variability and compensation in ion channel expression. Yet, little is known regarding the physiological consequences of morphological variability. We quantify animal-to-animal variability in cable lengths (CV = 0.4) and branching patterns in the Gastric Mill (GM) neuron, an identified neuron type with highly-conserved physiological properties in the crustacean stomatogastric ganglion (STG) of Cancer borealis. We examined passive GM electrotonic structure by measuring the amplitudes and apparent reversal potentials (Erevs) of inhibitory responses evoked with focal glutamate photo-uncaging in the presence of TTX. Apparent Erevs were relatively invariant across sites (mean CV ± SD = 0.04 ± 0.01; 7-20 sites in each of 10 neurons), which ranged between 100-800 µm from the somatic recording site. Thus, GM neurons are remarkably electrotonically compact (estimated λ > 1.5 mm). Electrotonically compact structures, in consort with graded transmission, provide an elegant solution to observed morphological variability in the STG.

Observation of Flexibility Reversal in DNA Bending

Several experiments on DNA looping show that DNA looping probability at short length scales is higher than the prediction of the wormlike chain model. This observation suggests that DNA becomes more flexible at large bending angles and hints at the possibility that sequence dependence of flexibility may not be universal across different bending regimes. Using a FRET-based DNA looping assay, we measured flexibilities of various DNA sequences (some of which include base pair mismatches) from the looping and unlooping rates. Surprisingly, we find a strong correlation between the measured looping and unlooping rates, which points to an apparent flexibility reversal: more flexible sequences in the unlooped state are more rigid in the looped state. To explain this counterintuitive finding, we present a few hypotheses that challenge our coarse-grained level understanding of DNA.

Stereoelectronic Chameleons: The Donor-Acceptor Dichotomy of Functional Groups.

Stereoelectronic factors account for the apparent reversal of donor-acceptor properties of a variety of functional groups by a simple change of their orientation in space. The new reactivity patterns that arise from spatial anisotropy are associated with chameleonic behavior of common organic functionalities.

The effect of display movement angle, indicator type and display location on control/display stereotype strength

Much research on stereotype strength relating display and control movements for displays moving in the vertical or horizontal directions has been reported. Here we report effects of display movement angle, where the display moves at angles (relative to the vertical) of between 0° and 180°. The experiment used six different controls, four display locations relative to the operator and three types of indicator. Indicator types were included because of the strong effects of the ‘scale-side principle’ that are variable with display angle. A directional indicator had higher stereotype strength than a neutral indicator, and showed an apparent reversal in control/display stereotype direction beyond an angle of 90°. However, with a neutral indicator this control reversal was not present.Practitioner Summary: The effects of display moving at angles other than the four cardinal directions, types of control, location of display and types of indicator are investigated. Indicator types (directional and neutral) have an effect on stereotype strength and may cause an apparent control reversal with change of display movement angle.

Simulating 2 Ga of geodynamo history

AbstractThe paleomagnetic record indicates the geodynamo has been active over much of Earth history with surprisingly little trend in paleointensity. Variability, however, is expected from models that predict a sharp increase in intensity following inner core nucleation (ICN) and implied by Neoproterozoic anomalies that hint at a highly variable field over several hundred million years. Here we demonstrate with a suite of numerical dynamos driven by a new thermal evolution model that the geodynamo could have transitioned from a multipolar to dipolar regime around 1.7 Ga, then to a weak‐field dynamo around 1.0 Ga, and finally to a strong‐field dipole following ICN around 650 Ma that is maintained to the present day. The occurrence of a weak‐field geodynamo in the Neoproterozoic may be consistent with the observed anomalous apparent polar wander paths and reversal behavior. Recovery to a dipolar geodynamo in the Phanerozoic could be a signature of inner core nucleation. Index terms: 1507, 1560, and 1521.

Pattern of Otorhinolaryngological Admissions via Emergency Unit in a Suburban Tertiary Center

Background: Patients with ORL lesions sometimes present to the general emergency room. This study reviews the common ENT admissions via emergency room in a sub-urban town in Nigeria. Methods: A retrospective study spanning five years from January 2009 to December 2013. Results: A total of 211 cases consisting of 131 (62.1%) males with male: female ratio 1.6: 1 and a mean age of 32.8 ± 22.4 years. About a quarter of the patients were children, the peak age was 21-40 years (in 37%). The common indications for emergency otorhinolaryngological admissions were Epistaxis (16.1%), Nasal/facial trauma (14.7%), pharyngo-esophageal foreign bodies (13.3%) and upper airway obstruction (8.1%). Majority 16 (57.1%) of the Pharyngo-esophageal FBs occurred in children. Most of the airway obstructions in children were due to juvenile recurrent respiratory papillomatosis while laryngeal cancer was the major cause among the adult. Sixty percent had surgical procedures, 86.7% had satisfactory outcome and mortalities were recorded in 1.4%. Conclusion: Majority of causes for ORL admissions via emergency unit are of pharyngo-esophageal origin. There is apparent reversal of the otological origin trend in ENT admissions via A&amp;E unit.