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The first 2 years of life is a period of rapid learning and growth when humans acquire notable motor, perceptual, linguistic, and social capabilities. Because of challenges in measuring brain activity in human infants, many of the neural mechanisms underlying these capabilities have not been identified. Advances in neuroimaging technologies, task designs, and data analyses from studies of older children and adults are starting to be translated into studies of infants. These new methods include frequency tagging designs in electroencephalography (EEG), task-based functional magnetic resonance imaging (fMRI) studies in awake and behaving infants, multivariate analyses of EEG and functional near-infrared spectroscopy (fNIRS), and the emergence of infant-friendly optically pumped magnetometry (OPM). The resulting neural data provide rich new measures of infant cognition, supplementing the limited behavioral data that can be obtained from preverbal infants. The functional properties of the infant brain are poorly understood. Recent advances in cognitive neuroscience are opening new avenues for measuring brain activity in human infants. These include novel uses of existing technologies such as electroencephalography (EEG) and magnetoencephalography (MEG), the availability of newer technologies including functional near-infrared spectroscopy (fNIRS) and optically pumped magnetometry (OPM), and innovative applications of functional magnetic resonance imaging (fMRI) in awake infants during cognitive tasks. In this review article we catalog these available non-invasive methods, discuss the challenges and opportunities encountered when applying them to human infants, and highlight the potential they may ultimately hold for advancing our understanding of the youngest minds. [ABSTRACT FROM AUTHOR]

Lumbar interbody instrumentation techniques are common and effective surgical options for a variety of lumbar degenerative pathologies. Anterior lumbar interbody fusion (ALIF) has become a versatile and powerful means of decompression, stabilization, and reconstruction. As an anterior only technique, the integrity of the posterior muscle and ligaments remain intact. Adding posterior instrumentation to ALIF is common and may confer benefits in terms of higher fusion rate but could contribute to adjacent segment degeneration due to additional rigidity. Large clinical studies comparing stand-alone ALIF with and without posterior supplementary fixation (ALIF+PSF) are lacking. To compare rates of operative nonunion and adjacent segment disease (ASD) in ALIF with or without posterior instrumentation. Retrospective cohort study. Adult patients (≥18 years old) who underwent primary ALIF for lumbar degenerative pathology between levels L4 to S1 over a 12-year period. Exclusion criteria included trauma, cancer, infection, supplemental decompression, noncontiguous fusions, prior lumbar fusions, and other interbody devices. Reoperation for nonunion and ASD compared between ALIF only and ALIF+PSF. Reoperations were modeled as time-to-events where the follow-up time was defined as the difference between the primary ALIF procedure and the date of the outcome of interest. Crude cumulative reoperation probabilities were reported at 5-years follow-up. Multivariable Cox proportional hazard regression was used to evaluate risk of operative nonunion and for ASD adjusting for patient characteristics. The study consisted of 1,377 cases; 307 ALIF only and 1070 ALIF+PSF. Mean follow-up time was 5.6 years. The 5-year crude nonunion incidence was 2.4% for ALIF only and 0.5% for ALIF+PSF; after adjustment for covariates, a lower operative nonunion risk was observed for ALIF+PSF (HR=0.22, 95% CI=0.06–0.76). Of the patients who are deemed potentially suitable for ALIF alone, one would need to add posterior instrumentation in 53 patients to prevent one case of operative nonunion at a 5-year follow-up (number needed to treat). Five-year operative ASD incidence was 4.3% for ALIF only and 6.2% for ALIF+PSF; with adjustments, no difference was observed between the cohorts (HR=0.96, 95% CI=0.54–1.71). While the addition of posterior instrumentation in ALIFs is associated with lower risk of operative nonunion compared with ALIF alone, operative nonunion is rare in both techniques (<5%). Accordingly, surgeons should evaluate the added risks associated with the addition of posterior instrumentation and reserve the supplemental posterior fixation for patients that might be at higher risk for operative nonunion. Rates of operative ASD were not statistically higher with the addition of posterior instrumentation suggesting concern regarding future risk of ASD perhaps should not play a role in considering supplemental posterior instrumentation in ALIF. [ABSTRACT FROM AUTHOR]

Pyoderma gangrenosum est une dermatose neutrophilique rare, se présentant par des ulcérations cutanées inflammatoires et douloureuses, riches en infiltrat à PNN, souvent prises pour des lésions infectieuses ou ischémiques, et le plus souvent localisées au niveau du tronc et des membres inférieurs. Dans la moitié des cas, il est associé à des pathologies inflammatoires ou onco-hématologiques. On note une forte association avec les pathologies inflammatoires digestives notamment. Pyoderma gangrenosum peut s'étendre à des tissus extra-cutanés, avec des atteinte pulmonaires ou articulaires. Nous rapportons ici le cas d'une patiente de 56 ans, prise en charge pour un Pyoderma gangrenosum pulmonaire. Elle avait pour principale antécédent une maladie de Crohn colique, non sténosante et non fibrosante, initialement traitée par infliximab, en combothérapie avec du méthotrexate. Les principales complications de ce traitement ont été, en 2020, une infection pulmonaire à mycobactérie atypique de type Xenopi traitée par quadrithérapie (azithromycine, éthambutol, clofazimine et isoniazide) et une aspergillose pulmonaire cavitaire apicale droite, traitée par voriconazole. Un relai de la combothérapie a également été réalisé, par du védolizumab, sans un contrôle entièrement satisfaisant de l'activité de la maladie de Crohn. Dans le cadre du suivi pneumologique, malgré une évolution scanographique initiale favorable et la poursuite du voriconazole, un PET-scanner avait mis en évidence la persistance d'un épaississement de la paroi avec un hypermétabolisme de la cavité apicale droite. Par la suite, du fait d'une évolution défavorable avec un nouveau contrôle scanographique en faveur d'un comblement cavitaire et d'une extension de l'atteinte en sous-pleural, une bronchoscopie a été réalisée. Des sécrétions purulentes ont été retrouvées, avec des prélèvements bactériologiques, mycologiques et mycobactériologiques négatifs. L'anatomopathologie éliminait une lésion néoplasique bronchique et concluait à un matériel de lavage légèrement inflammatoire à polynucléaires neutrophiles. Le diagnostic de Pyoderma gangrenosum a été posé, et après discussion entre les pneumologues et les gastro-entérologues, l'introduction d'un traitement commun à l'atteinte digestive et pulmonaire par upadacitinib 30 mg a été décidée. Le contrôle scanographique à un mois était en faveur d'une diminution du comblement et de l'épaisseur de la paroi de la cavité pulmonaire. On notait également un contrôle satisfaisant de l'inflammation digestive. Les anti-JAK sont de plus en plus présents dans notre pratique et dans l'arsenal thérapeutique de différentes spécialités, avec une efficacité plus ou moins démontrée dans les atteintes inflammatoires dermatologiques, rhumatologiques et gastro-entérologiques notamment. Favoriser les discussions collégiales pluridisciplinaires permettrait un meilleur contrôle d'atteintes inflammatoires multiples, avec un traitement unique. [ABSTRACT FROM AUTHOR]

We hollow out a given completely regular frame L by removing, for an uncountable regular cardinal number κ , the dense κ -cozero elements of L. This we do by passing to the cointersection of the proper dense open κ -cozero quotients of L. The quotient frame is κ-hollow, i.e., it has no proper dense κ -cozero elements, and this passage is a bireflection in the category of frames with skeletal morphisms. Thus each frame L has a descending sequence of dense quotient frames of increasing hollowness, indexed by the uncountable regular cardinal numbers, culminating in the classical minimal dense quotient of L. Our purpose is to shed light on the structure of a given frame L by examining the collection of quotients and sub- κ -frames which arise in its hollowing sequence, to which we refer collectively as the scaffolding of L. [ABSTRACT FROM AUTHOR]

Humans make predictions about future events in many domains, including when they listen to music. Previous accounts of harmonic expectation in music have emphasised the role of implicit musical knowledge acquired in the long term through the mechanism of statistical learning. However, it is not known whether listeners can adapt their expectations for unusual harmonies in the short term through repetition priming, and whether the extent of any short-term adaptation depends on the unfolding statistical structure of the music. To explore these possibilities, we presented 150 participants with phrases from Bach chorales that ended with a cadence that was either a priori likely or unlikely based on the long-term statistical structure of the corpus of chorales. While holding the 50–50 incidence of likely vs. unlikely cadences constant, we manipulated the order in which these phrases were presented such that the local probability of hearing an unlikely cadence changed throughout the experiment. For each phrase, participants provided two judgements: (a) a prospective rating of how confident they were in their expectations for the cadence, and (b) a retrospective rating of how well the presented cadence matched their expectations. While confidence ratings increased over the course of the experiment, the rate of change decreased as the local probability of an unexpected cadence increased. Participants' expectations favoured likely cadences over unlikely cadences on average, but their expectation ratings for unlikely cadences increased at a faster rate over the course of the experiment than for likely cadences, particularly when the local probability of hearing an unlikely cadence was high. Thus, despite entrenched long-term statistics about cadences, listeners can indeed adapt to unusual musical harmonies and are sensitive to the local statistical structure of the musical environment. We suggest that this adaptation is an instance of Bayesian belief updating, a domain-general process that accounts for expectation adaptation in multiple domains. [ABSTRACT FROM AUTHOR]

Why do states become theocracies? Johnson and Koyama (2019) analyzed the transition from a conditional-toleration equilibrium, in which feeble state capacity allows distinct religious groups to co-exist under a system of religion-based identity rules, to a religious-toleration equilibrium, in which a strong state applies secular general rules without the need for religion as a legitimizing force. This implies that religious legitimacy and high state capacity are substitutes. We explore the alternative possibility that religious legitimacy and a strong state can be complements; that is, religion and high state capacity work together to extract resources from the citizenry. The result is an equilibrium of religious rather than secular general rules in which high state capacity and religion reinforce each other—a theocracy. An empirical analysis of the transition from premodern to modern theocracy, based on a unique dataset of religion and politics in world history, indicates that the adoption of general rules in the modern era differed systematically between societies in which strong state capacity was a complement rather than a substitute for religion. [ABSTRACT FROM AUTHOR]

Mounting behavioral evidence suggests that declines in both representational quality and controlled retrieval processes contribute to episodic memory decline with age. The present study sought neural evidence for age-related change in these factors by measuring neural differentiation during encoding of paired associates and changes in regional blood oxygenation level–dependent activity and functional connectivity during retrieval conditions that placed low (intact pairs) and high (recombined pairs) demands on controlled retrieval processes. Pattern similarity analysis revealed age-related declines in the differentiation of stimulus representations at encoding, manifesting as both reduced pattern similarity between closely related events and increased pattern similarity between distinct events. During retrieval, both groups increased recruitment of areas within the core recollection network when endorsing studied pairs, including the hippocampus and angular gyrus. In contrast, only younger adults increased recruitment of, and hippocampal connectivity with, lateral prefrontal regions during correct rejections of recombined pairs. These results provide evidence for age-related changes in representational quality and in the neural mechanisms supporting memory retrieval under conditions of high, but not low, control demand. • Memory decline with age may relate to representational quality and strategic retrieval. • We tested memory performance along with univariate and multivariate fMRI measures. • Neural evidence for reduced representational specificity at encoding and retrieval. • Deficits also observed in neural mechanisms underlying controlled strategic retrieval. • Memory decline linked to representational content and strategic retrieval processes. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance disseminates throughout bacterial populations via horizontal gene transfer, driven mainly by mobile genetic elements (MGEs). Entrapment vectors are key tools in determining MGE movement within a bacterial cell between different replicons or between sites within the same replicon. The pBACpAK entrapment vector has been previously used to study intracellular transfer in Gram-negative bacteria however since pBACpAK contains a chloramphenicol resistance gene, it cannot be used in bacterial isolates which are already resistant to chloramphenicol. Therefore, we developed new derivatives of the pBACpAK entrapment vector to determine intracellular transfer of MGEs in an Escherichia coli DH5α transconjugant containing the chloramphenicol resistance plasmid pD25466. The catA1 of pBACpAK was replaced by both mcr-1 in pBACpAK-COL and aph(3′)-Ia in pBACpAK-KAN, allowing it to be used in chloramphenicol resistant strains. The plasmid constructs were verified and then used to transform the E. coli DH5α/pD25466 transconjugants in order to detect intracellular movement of the MGEs associated with the pD25466 plasmid. Here we report on the validation of the expanded suite of pBACpAK vectors which can be used to study the intracellular transfer of MGEs between, and within, replicons in bacteria with different antimicrobial resistance profiles. [ABSTRACT FROM AUTHOR]

The recent rise in opioid-related overdose deaths stresses the importance of understanding how heroin use disorders persist and what interventions are best suited for treating these illnesses. Trends show that there are diverse pathways leading to heroin use disorder that span multiple generations, but little is known about how different generations utilize and respond to treatment. This study provides insight into treatment utilization for young, middle-aged, and older adults by examination of an unusually rich longitudinal dataset of substance use disorder clients in Maryland who were treated for heroin use. Results show that clear patterns of treatment readmission emerge across generations in treatment-naïve clients with regard to gender, ethnicity, employment, geographical region, and treatment type/intensity. In particular, Millennials comprise the majority of the clients receiving heroin use disorder treatment and are the largest contributor to these readmission patterns. Millennials are also given opioid maintenance therapy (OMT) more frequently than other generations, while exhibiting a strong avoidance to treatment. Generational differences in treatment decisions and outcomes over the course of a treatment career are important for understanding the nature of the current opioid epidemic, and can play an important role in directing heroin use disorder treatment efforts and improving models of care. [ABSTRACT FROM AUTHOR]

Volcanic eruptions that are not historically attested are often dated by "wiggle matching" sequential radiocarbon measurements of the rings of trees killed by the eruption against a calibration curve. Although evidence for contamination by exposure to 14C-free geogenic carbon is well documented, it is generally assumed that the radiocarbon ages are unbiased by such "old" carbon. The 'Millennium Eruption' of Changbaishan / Paektu volcano (China/DPR Korea) provides an opportunity to test this assumption, since several age estimates were made before the acceptance of a precise eruption year of 946 CE. Accordingly, we develop a methodology that enables testing of assumptions and evaluation of discrepancies between reported wiggle match series. We then use it to correct for contamination levels of up to 4.5% old carbon to eight wiggle match date series for the Millennium Eruption. Without the need to discard ring ages, we find agreement indices as high as, or higher than, those for the published dates. Five of the eight series yielded high-agreement-index eruption dates closer to 946 CE than the published dates. None of the five yielded a best result without recognising some degree of contamination. Differences between the eruption dates reveal a weak association with the direction of the sampled tree from the caldera, but no relationship with distance. Our results suggest that old carbon contamination can lead to over-estimation of eruption ages by years, decades, or more. In addition, our results show that anomalously younger ages can also be a problem in radiocarbon series and these cannot be easily overcome at present by this methodology. [ABSTRACT FROM AUTHOR]

Background: Direct current cardioversion is a common management option for termination of tachydysrhythmias, including atrial fibrillation and atrial flutter. It is generally safe and effective with infrequent reporting of side effects. Pulmonary edema is a rare complication with reported incidence of 1-3% and mortality of 18%. Our literature search did not reveal any reported cases of postcardioversion pulmonary edema in the emergency medicine literature.Case Report: We report a case of an 80-year-old woman with a history of atypical atrial flutter on warfarin, paroxysmal atrial fibrillation, and rheumatic mitral valve disease who presented with shortness of breath 12 h after transesophageal echocardiography and subsequent direct current cardioversion with reversion to sinus rhythm. She was found to be in acute pulmonary edema. She was placed on noninvasive ventilation and diuresis with eventual symptom resolution. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Postcardioversion pulmonary edema is a rare complication that may occur after reversion to sinus rhythm. Emergency physicians should be cognizant of patients, especially those with underlying structural heart disease, who present with dyspnea after a recent cardioversion procedure or after cardioversion in the emergency department. Patients cardioverted in the emergency department may be observed for around 3 h and counseled on the development of respiratory symptoms. [ABSTRACT FROM AUTHOR]

Background: Epidural injections are routinely used for management of radicular pain and are prevalent nonsurgical interventions for chronic low back pain. Pneumocephalus is a rare complication that may occur as a result of inadvertent dural puncture with an epidural needle. Pneumocephalus-induced cranial nerve deficit is also rare, with only a few reported cases.Case Report: We report a case of a 61-year-old woman with a chief complaint of diplopia after she underwent epidural injection for chronic lumbar pain. Her examination was remarkable for a partial right oculomotor nerve palsy. We obtained a computed tomography brain scan, which revealed pneumocephalus. She was managed conservatively and reported complete symptom resolution after 2 weeks. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Pneumocephalus is an uncommon complication of epidural spinal injections. Emergency physicians should include this on the differential for a patient presenting with cranial nerve deficit after this procedure. [ABSTRACT FROM AUTHOR]

Effective urban planning depends on knowing homebuyers' preferences for neighbourhood features that provide different amenities, such as managed parks and trees. As the expansion of tropical urban areas into biodiversity hotspots is predicted to more than double by 2030, knowing homebuyers utility from different vegetation types can contribute to global biodiversity conservation strategies. We used the hedonic pricing method to estimate the economic value of managed, spontaneous and high conservation value vegetation to Singapore public housing using a mixed effects model. On average vegetation had positive effects on property selling price, accounting for 3% of the average property's value, or a total of S$179 million for all public housing apartments sold over 13 months. These effects were almost entirely driven by managed vegetation, which had positive marginal effects on price for 98.1% of properties. The estimated marginal effects of high conservation value vegetation were mostly negative (90.5%% properties), but positive for properties without much managed vegetation nearby. The estimated marginal effects of spontaneous vegetation were mixed and mostly small. To reconcile the goals of protecting high conservation value vegetation and maximising homeowner utility, new public housing developments should contain more managed vegetation but be away from high conservation value vegetation. [ABSTRACT FROM AUTHOR]

Nitrate concentration in most aquifers in arid and semi-arid areas has increased in the past several decades as a result of human activities. Under the predominantly oxic conditions of these aquifers, denitrification is inhibited, allowing nitrate, a soluble and stable form of nitrogen (N), to accumulate. Because of its close association with municipal and agricultural wastes, nitrate is commonly used as an indicator of anthropogenic contamination. Aquifers affected by agricultural waste may contain salts from irrigation returns and herbicides in addition to nitrates. Preventing leakage from soil to deeper parts of the aquifer is thus a priority in the sustainable management of aquifers in arid and semiarid areas. Studies report a wide range of nitrate concentrations distributed non-uniformly within the aquifer, with roughly 40% and 20% of sampled wells exceeding 50 mg/L nitrate in shallow and deep parts of the aquifer respectively. In aquifers at risk of becoming contaminated, nitrate isotopes (δ 15 N, δ 18 O, Δ 17 O) can be used to identify the source of nitrogen as mineral or organic fertilizer, sewage, or atmospheric deposition. A variety of mathematical models (crop, hydrological, geochemical, or a combination of them) have been successful in identifying best practices that minimize N leakage without negatively affecting crop yield. In addition, field research in crop management, e.g., conservation agriculture, has yielded promising results in determining the adequate dosage and time of application of fertilizers to reduce N losses. Examples of key dryland aquifers impacted by nitrate are discussed, and some of the most pressing challenges to achieve sustainability are presented. [ABSTRACT FROM AUTHOR]

Background: Crohn's disease often requires intestinal resection, which is not considered curative. Repeat surgical intervention is necessary in more than half of patients after their initial operation. Although many genetic loci are implicated in Crohn's disease, few have been associated with post-resection recurrence.Study Design: A cohort of patients with Crohn's disease who underwent intestinal resection was analyzed to determine genetic and clinical factors associated with post-resection recurrence. Genotype was assessed at 8 loci associated with adaptive immunity (SMAD3, IL10RB, IL15RA, BACH2, IL12B, IL18RAP, IFNGR2, and JAK2). Univariate and multivariable survival analyses were performed using a log-rank test and Cox-proportional hazard model, respectively.Results: One hundred and ninety-one patients with Crohn's disease and 11.2 years mean postoperative follow-up were included. Forty-six percent experienced a surgical recurrence. Factors associated with increased incidence of recurrence included male sex (p = 0.05) and shortened time to first intestinal operation (5.0 vs 7.3 years; p = 0.03); inflammatory disease behavior was associated with a lower chance of repeat operation (p < 0.01). Of the loci assessed on multivariable analysis, homozygosity for a risk allele at BACH2 (rs1847472) was significantly associated with disease recurrence (hazard ratio 1.54; 95% CI 1.00 to 2.36; p < 0.05).Conclusions: We identify BACH2 as a susceptibility locus for postoperative recurrence of Crohn's disease in our cohort. BACH2 is critical in the differentiation and function of T cells, as a regulator of B-cell activity, and is associated with several dysregulated immunologic phenomena. Its identification as a risk locus in postoperative Crohn's disease recurrence suggests a potential role for regulatory T cells, effector T cells, humoral immunity, and immunologic memory in the development of this disease process. [ABSTRACT FROM AUTHOR]

Background Parenteral prostacyclin analogs that target the prostacyclin pathway have been used to treat pulmonary arterial hypertension (PAH) since the 1990s. Abrupt discontinuation of parenteral prostacyclin analogs can be associated with acute deterioration of PAH. Less is known about temporary interruption of oral therapies that target the prostacyclin pathway, such as selexipag. Methods We evaluated the frequency, duration, reasons, and consequences of temporary selexipag interruptions among PAH patients enrolled in the Prostacyclin (PGI 2 ) Receptor Agonist in Pulmonary Arterial Hypertension (GRIPHON) study. In GRIPHON, patients were randomized to selexipag or placebo and titrated to an individualized highest tolerated dose (200 to 1,600 µg twice daily) over 12 weeks, after which patients entered the maintenance phase. Treatment interruptions were allowed; if the interruption was < 3 days, treatment was restarted at the previous highest tolerated dose; if the interruption was ≥ 3 days, retitration from 200 µg twice daily was required. Descriptive analyses were performed. Results At least 1 treatment interruption occurred in 111 of 574 patients (19.3%) in the selexipag group and in 58 of 582 (10.0%) in the placebo group. Baseline characteristics were similar between patients with and without an interruption. Of the 111 patients in whom selexipag was temporarily interrupted, 94 (85%) were receiving background PAH therapy. Adverse events were the most common reason for selexipag interruption. Selexipag interruptions and reinstitution of treatment were well tolerated. There were no episodes of acute deterioration during treatment interruption. Conclusions Based on observations from GRIPHON, selexipag interruptions can be expected in clinical practice. However, temporarily interrupting selexipag was well tolerated and manageable. [ABSTRACT FROM AUTHOR]

We define pointfree pointwise convergence, and use it to define the Baire functions on a locale. The main result is that the Baire functions on a locale coincide with the continuous functions on its P -locale coreflection. Furthermore, we show that the Baire functions on a locale constitute the epicompletion of the continuous functions in the relevant category. The relevant category is T , the category of truncated archimedean ℓ -groups, hereafter nicknamed truncs. T is closely related to the famous category W of unital archimedean ℓ -groups. The universal objects in T are of the form R 0 L , the trunc of real-valued locale maps L → R which vanish at the designated point of a pointed locale L . We provide an intuitive definition of pointwise convergence in R 0 L which extends the classical definition, and show that it has a number of nice properties: all homomorphisms and operations of T are pointwise continuous, and a pointwise dense extension is a trunc epimorphism. Conversely, we show that every epic extension G → H has an epic extension H → K such that G is pointwise dense in K . We show that the rich theory of epimorphisms in W carries over to T with only minor modification. In particular, the epicomplete truncs comprise a full monoreflective subcategory, and are characterized as those objects of the form R 0 P for a P -locale P . In light of these facts, a reformulation of the last clause of the preceding paragraph is that any trunc is pointwise dense in any epicompletion. And a trunc is epicomplete iff it is pointwise complete, i.e., has no proper extension in which it is pointwise dense. Finally, for a given pointed locale L , we define the functions of Baire class α on L in the classical fashion. A function is Baire class 0 if it lies in R 0 L , and of Baire class β if it is the pointwise limit of a sequence of functions of Baire class α < β . A Baire function on L is a function of Baire class α for some α . Our results can be summarized as follows. Theorem For a pointed locale L with P-locale coreflection P ⁎ L → L , the Baire functions on L are precisely the continuous functions on P ⁎ L , i.e., those of R 0 P ⁎ L . Theorem The embedding R 0 L → R 0 P ⁎ L is the functorial epicompletion in T . [ABSTRACT FROM AUTHOR]

Mutations in splicing factor genes ( SF3B1 , SRSF2 , U2AF1 and ZRSR2 ) are frequently found in patients with myelodysplastic syndromes (MDS), suggesting that aberrant spliceosome function plays a key role in the pathogenesis of MDS. Splicing factor mutations have been shown to result in aberrant splicing of many downstream target genes. Recent functional studies have begun to characterize the splicing dysfunction in MDS, identifying some key aberrantly spliced genes that are implicated in disease pathophysiology. These findings have led to the development of therapeutic strategies using splicing-modulating agents and rapid progress is being made in this field. Splicing inhibitors are promising agents that exploit the preferential sensitivity of splicing factor-mutant cells to these compounds. Here, we review the known target genes associated with splicing factor mutations in MDS, and discuss the potential of splicing-modulating therapies for these disorders. [ABSTRACT FROM AUTHOR]

The reduction potential of Fe(II)-Fe(III) (oxyhydr)oxide systems provides an important control on the biogeochemical cycling of redox-sensitive elements such as carbon and nitrogen as well as trace metals and organic contaminants in natural systems. As such, an in-depth understanding of the factors controlling the reduction potential of such systems is critical to predicting the likely transformation, transport and fate of these species in natural and perturbed environments. In this study the mineralogy and reduction potential of ferrihydrite suspensions at pH 6.50 and pH 7.00 were determined over the course of their Fe(II)-catalyzed transformation to lepidocrocite and goethite using X-ray absorption spectroscopy and mediated electrochemical approaches. The measured reduction potentials were compared to those of analogous Fe(II)-Fe(III) (oxyhydr)oxide suspensions reacted for 5 min containing pure ferrihydrite (Fh), lepidocrocite (L) and goethite (Gt). The reduction potentials of the pure Fe(II)-Fe(III) (oxyhydr)oxide suspensions were, respectively, +47.5, −13.5 and −122.3 mV vs. SHE at pH 6.5, and −22.9, −84.1 and −189.7 mV vs. SHE at pH 7. These values are in good agreement with reduction potentials calculated using the Nernst equation and reported thermodynamic solubility products indicating that these suspensions had reached equilibrium within 5 min. The reduction potential of the pH 6.50 Fe(II)-ferrihydrite suspension decreased from +47.4 mV to –126.4 mV over a week, and from −20.1 mV to −188.4 mV (all vs. SHE) after 24 h at pH 7. The changes in reduction potential over time matched well to those calculated from the relative proportion of each pure Fe(III) (oxyhydr)oxide present suggesting that Fe 3+ activity was influenced by the mix of iron oxides present rather than the most insoluble solid species. Finally, evidence is provided that adsorbed Fe(II) has the capacity to reduce a significantly larger fraction of a reducible species than the aqueous Fe(II) species with which it is in equilibrium. As an Fe(III) (oxyhydr)oxide suspension in equilibrium with aqueous and adsorbed Fe(II) species possesses a single, unique reduction potential, this suggests that adsorbed Fe(II) is a more facile reductant than aqueous Fe(II). [ABSTRACT FROM AUTHOR]

The cancer multidrug resistance (MDR) phenotype encompasses a myriad of molecular, genetic and cellular alterations resulting from progressive oncogenic transformation and selection. Drug efflux transporters, in particular the MDR P-glycoprotein ABCB1, play an important role in MDR but cannot confer the complete phenotype alone indicating parallel alterations are prerequisite. Sphingolipids are essential constituents of lipid raft domains and directly participate in functionalization of transmembrane proteins, including providing an optimal lipid microenvironment for multidrug transporters, and are also perturbed in cancer. Here we postulate that increased sphingomyelin content, developing early in some cancers, recruits and functionalizes plasma membrane ABCB1 conferring a state of partial MDR, which is completed by glycosphingolipid disturbance and the appearance of intracellular vesicular ABCB1. In this review, the independent and interdependent roles of sphingolipid alterations and ABCB1 upregulation during the transformation process and resultant conferment of partial and complete MDR phenotypes are discussed. [ABSTRACT FROM AUTHOR]

Transplantations of various stem cells or their progeny have repeatedly improved cardiac performance in animal models of myocardial injury; however, the benefits observed in clinical trials have been generally less consistent. Some of the recognized challenges are poor engraftment of implanted cells and, in the case of human cardiomyocytes, functional immaturity and lack of electrical integration, leading to limited contribution to the heart's contractile activity and increased arrhythmogenic risks. Advances in tissue and genetic engineering techniques are expected to improve the survival and integration of transplanted cells, and to support structural, functional, and bioenergetic recovery of the recipient hearts. Specifically, application of a prefabricated cardiac tissue patch to prevent dilation and to improve pumping efficiency of the infarcted heart offers a promising strategy for making stem cell therapy a clinical reality. [ABSTRACT FROM AUTHOR]

The hippocampus is believed to be important for rapid learning of arbitrary stimulus-response contingencies, or S-R bindings. In support of this, Schnyer et al. (2006) (Experiment 2) measured priming of reaction times (RTs) to categorise visual objects, and found that patients with medial temporal lobe damage, unlike healthy controls, failed to show evidence of reduced priming when response contingencies were reversed between initial and repeated categorisation of objects (a signature of S-R bindings). We ran a similar though extended object classification task on 6 patients who appear to have selective hippocampal lesions, together with 24 age-matched controls. Unlike Schnyer et al. (2006), we found that reversing response contingencies abolished priming in both controls and patients. Bayes Factors provided no reason to believe that response reversal had less effect on patients than controls. We therefore conclude that it is unlikely that the hippocampus is needed for S-R bindings. [ABSTRACT FROM AUTHOR]

The use of leaderboards is a common approach to the gamification of employee performance, but little is known about the specific mechanisms and mediating processes by which leaderboards actually affect employee behavior. Given the lack of research in this domain, this study proposes goal-setting theory, one of the most well-established motivational theories in psychology, as a framework by which to understand these effects. In this study, a classic brainstorming task is gamified with a leaderboard in order to explore this. Participants were randomly assigned to four classic levels of goal-setting (do-your-best, easy, difficult and impossible goals) plus a leaderboard populated with initials and scores representing identical goal-setting conditions. The presence of a leaderboard was successful in motivating participants to performance levels similar to that of difficult and impossible goal-setting, suggesting participants implicitly set goals at or near the top of the leaderboard without any prompting to do so. Goal commitment, a common individual difference moderator in goal-setting theory, was also assessed and behaved similarly in the presence of the leaderboard as when traditional goals were provided. From these results, we conclude that goal-setting theory is valuable to understand the success of leaderboards, and we recommend further exploration of existing psychological theories, including goal-setting, to better explain the effects of gamification. [ABSTRACT FROM AUTHOR]

Background Gamification, the use of game elements in non-game contexts, has become a popular technique to improve instructional outcomes in both organizational and educational contexts. In the organizational context, the Technology-Enhanced Training Effectiveness Model [TETEM] provides a framework to understand how technologies, like gamification, can effect change in various instructional outcomes. Specifically, application of TETEM suggests that gamification may not effect change in instructional outcomes when learner attitudes towards game-based learning and experience with video games are low. Method In this study, we test this model in the gamification context by assigning potential learners to read scenarios describing gamified instruction or traditional, PowerPoint instruction in a random order and assessing their training valence. Results On average, participants anticipated greater value from gamified instruction, but as predicted by TETEM, this effect was moderated by both video game experience and attitudes towards game-based learning. Among potential learners with high experience and attitudes, gamification produces better outcomes than PowerPoint, but among potential learners with low experience and attitudes, gamification produces worse outcomes than PowerPoint. Implications We provide empirical support for TETEM and conclude that for gamification to be successful, the attitudes and experience of participants must be assessed and ensured before gamification is implemented. [ABSTRACT FROM AUTHOR]

The energy released by failure of rechargeable 18-mm diameter by 65-mm long cylindrical (18650) lithium ion cells/batteries was measured in a bomb calorimeter for 4 different commercial cathode chemistries over the full range of charge using a method developed for this purpose. Thermal runaway was induced by electrical resistance (Joule) heating of the cell in the nitrogen-filled pressure vessel (bomb) to preclude combustion. The total energy released by cell failure, Δ H f , was assumed to be comprised of the stored electrical energy E (cell potential × charge) and the chemical energy of mixing, reaction and thermal decomposition of the cell components, Δ U rxn . The contribution of E and Δ U rxn to Δ H f was determined and the mass of volatile, combustible thermal decomposition products was measured in an effort to characterize the fire safety hazard of rechargeable lithium ion cells. [ABSTRACT FROM AUTHOR]

The use and development of the investigative tool colloquially known as criminal profiling has steadily increased over the past five decades throughout the world. Coupled with this growth has been a diversification in the suggested range of applications for this technique. Possibly the most notable of these has been the attempted transition of the technique from a tool intended to assist police investigations into a form of expert witness evidence admissible in legal proceedings. Whilst case law in various jurisdictions has considered with mutual disinclination the evidentiary admissibility of criminal profiling, a disjunction has evolved between these judicial examinations and the scientifically vetted research testing the accuracy (i.e., validity) of the technique. This article offers an analysis of the research directly testing the validity of the criminal profiling technique and the extant legal principles considering its evidentiary admissibility. This analysis reveals that research findings concerning the validity of criminal profiling are surprisingly compatible with the extant legal principles. The overall conclusion is that a discrete form of crime behavioural analysis is supported by the profiler validity research and could be regarded as potentially admissible expert witness evidence. Finally, a number of theoretical connections are also identified concerning the skills and qualifications of individuals who may feasibly provide such expert testimony. [ABSTRACT FROM AUTHOR]

Heart failure, whether acute or chronic, remains a major health care crisis affecting almost 6 million Americans and over 23 million people worldwide. Roughly half of those affected will die within 5 years, and the annual cost exceeds $30 billion in the US alone. Although medical therapy has made some modest inroads in partially stemming the heart failure tsunami, there remains a significant population for whom medication is unsuccessful or has ceased being effective; such patients can benefit from heart transplantation or mechanical circulatory support. Indeed, in the past quarter century (and as covered in Cardiovascular Pathology over those years), significant improvements in pathologic understanding and in engineering design have materially enhanced the toolkit of options for such refractory patients. Mechanical devices, whether total artificial hearts or ventricular assist devices, have been reengineered to reduce complications and basic wear and tear. Transplant survival has also been extended through a better comprehension of and improved therapies for transplant vasculopathy and antibody-mediated rejection. Here we review the ideas and treatments from the last 25 years and highlight some of the new directions in nonpharmacologic heart failure therapy. [ABSTRACT FROM AUTHOR]

A 2011 randomized controlled trial compared the effectiveness of two brief motivation-enhancing therapy (MET) models among alcohol-positive adolescents in an urban emergency department: adolescent MET-only versus MET + Family Check-Up (FCU), a parent MET model. Results indicated that among the 97 adolescents completing the 3-month assessment, both conditions were associated with reduced drinking and MET+FCU was associated with lower rates of high volume drinking than adolescent MET-only. The goal of this study was to identify predictors and moderators of high volume drinking in the original trial. Seven candidate variables were evaluated as moderators across three domains: demographic characteristics, psychological factors, and socio-contextual factors. Analyses of covariance models identified one significant predictor and one significant moderator of outcome. Older adolescents had significantly worse drinking outcomes than younger adolescents regardless of MET condition. Adolescents whose parents screened positive for problematic alcohol use at baseline had significantly worse drinking outcomes in the MET+FCU condition than the MET-only condition. Results indicate that alcohol-positive adolescents presenting to the emergency department may respond better to MET models if they are under the age of 16. Involving parents who have problematic alcohol use in a parent-focused MET may have negative effects on adolescent high volume drinking. [ABSTRACT FROM AUTHOR]

The use and development of the investigative tool colloquially known as criminal profiling has steadily increased over the past five decades throughout the world. Coupled with this growth has been a diversification in the suggested range of applications for this technique. Possibly the most notable of these has been the attempted transition of the technique from a tool intended to assist police investigations into a form of expert witness evidence admissible in legal proceedings. Whilst case law in various jurisdictions has considered with mutual disinclination the evidentiary admissibility of criminal profiling, a disjunction has evolved between these judicial examinations and the scientifically vetted research testing the accuracy (i.e., validity) of the technique. This article offers an analysis of the research directly testing the validity of the criminal profiling technique and the extant legal principles considering its evidentiary admissibility. This analysis reveals that research findings concerning the validity of criminal profiling are surprisingly compatible with the extant legal principles. The overall conclusion is that a discrete form of crime behavioural analysis is supported by the profiler validity research and could be regarded as potentially admissible expert witness evidence. Finally, a number of theoretical connections are also identified concerning the skills and qualifications of individuals who may feasibly provide such expert testimony. [ABSTRACT FROM AUTHOR]

In operational engineering maintenance situations, limitations on time, resource or the information available often inhibit rigorous analysis on complex decision problems. Decision-makers who are compelled to act in such circumstances, may be informed by some level of analysis if available, or else may have to rely on their unsupported judgement. This paper presents three engineering risk decision-making case studies across a 20 year span from the rail, aerospace, and military aviation contexts, highlighting the fallibilities of using unsupported judgements in an unstructured manner. To help situate this type of decision situation, we provide a descriptive model of the decision space which extends an existing description from the discipline of decision analysis. Furthermore, to help make and describe the distinction between unsupported and supported thinking, we provide another descriptive model, this time drawing parallels with the distinction made between Type 1 and Type 2 reasoning. This model is an extension of the default-interventionist model from cognitive psychology. The paper concludes that there is a pressing need to provide some form of support to engineering decision-makers facing operational decisions under severe time pressure. While the ultimate aim must be to improve the quality of decision-making, improved transparency is an important additional benefit. Increased emphasis on decision justification and self-awareness are suggested as potential ways of improving this situation. A further contribution of this paper is to identify and strengthen linkages between safety science and two other relevant disciplines, decision analysis and psychology. Such linkages make it easier to communicate across traditional disciplinary boundaries and may provide opportunities for interdisciplinary learning or suggest future directions for collaborative research. • Three engineering case studies highlight operational constraints on decisions. • Attention is focused on unsupported operational decision-making. • Extended decision space model provides a linkage with decision analysis. • Extended default-interventionist model provides a linkage with psychology. • Organisational risk systems are unable to cater adequately for unsupported judgement. [ABSTRACT FROM AUTHOR]

Using a novel combination of in situ potentiometric experiments and quick-scanning XAS we present Fe K-edge XAS spectra (to k = 12 Å −1 ) during Fe III hydrolysis and precipitation in 0.33 M Fe(ClO 4 ) 3 , Fe(NO 3 ) 3 , FeCl 3 and Fe 2 (SO 4 ) 3 solutions up to pH 4.8. Edge-sharing Fe III polymers appeared almost immediately upon hydrolysis with strong evidence for a μ-oxo dimer species forming in the Fe(ClO 4 ) 3 , Fe(NO 3 ) 3 and FeCl 3 solutions. The effects of SO 4 on hydrolysis and polymerization pathways included inhibition of both the formation of the μ-oxo dimer and double corner Fe III bonding, ultimately resulting in the precipitation of schwertmannite. As such, under these experimental conditions, double corner Fe III bonding appears to be critical to the formation of ferrihydrite. The spectral trends indicated that the decomposition/transformation of the dimer was sudden and broadly coincident with shortening average Fe–O bond distances, increased Fe neighbors at ∼3.43 Å and a pre-edge energy transformation suggestive of decreased ligand field strength as well as increasing proportions of tetrahedral Fe III . This result suggests that the incorporation of tetrahedral Fe III into ferrihydrite occurs only at the latter stages of extended polymerization. [ABSTRACT FROM AUTHOR]

Processes leading to the development of coastal hypoxia are usually attributed to anthropogenic nutrient loading. We present new evidence documenting a natural process capable of producing large-scale water masses undersaturated with respect to dissolved oxygen, independent of human-caused nutrient loading and subsequent nutrient-enhanced productivity. Along the heavily developed coastline of Myrtle Beach, South Carolina, the offshore discharge of saline, anoxic groundwater generates undersaturated bottom water masses which can be advected into nearshore waters. Highly elevated radium isotope activities measured in low-oxygen bottom waters cannot be supported by any known terrestrial source. Rather, discharge of cold, anoxic, high-radium water from offshore carbonate aquifers is the likely source. Density stratification inhibits mixing of these discharged waters during inshore transport. During a low-oxygen event in August 2012, this restricted mixing is likely the mechanism for the observed oxygen deficit in bottom waters. This discovery suggests benthic layers undersaturated with respect to dissolved oxygen may be considerably more prevalent than currently recognized, particularly around the carbonate-platform of the US East Coast. [ABSTRACT FROM AUTHOR]

We generalize the concept of the pointwise supremum of real-valued functions to the pointfree setting. The concept itself admits a direct and intuitive formulation which makes no mention of points. But our aim here is to investigate pointwise suprema of subsets of R L , the family of continuous real valued functions on a locale, or pointfree space. Thus our setting is the category W of archimedean lattice-ordered groups ( ℓ -groups) with designated weak order unit, with morphisms which preserve the group and lattice operations and take units to units. This is an appropriate context for this investigation because every W -object can be canonically represented as a subobject of some R L . We show that the suprema which are pointwise in the Madden representation can be characterized purely algebraically. They are precisely the suprema which are context-free, in the sense of being preserved by every W homomorphism out of G . We show that closure under such suprema characterizes the W -kernels among the convex ℓ -subgroups. Finally, we prove that all existing joins in a W -object G are pointwise iff its Madden frame L is boolean, and that all existing countable joins in G are pointwise if L is a P -frame, but not conversely. This leads up to the appropriate analog of the Nakano–Stone Theorem: a (completely regular) locale L has the feature that R L is conditionally pointwise complete ( σ -complete), i.e., every bounded (countable) family from R L has a pointwise supremum in R L , iff L is boolean (a P -locale). We adopt a maximally broad definition of unconditional pointwise completeness ( σ -completeness): a divisible W -object G is pointwise complete ( σ -complete) if it contains a pointwise supremum for every subset which has a supremum in any extension. We show that the pointwise complete ( σ -complete) W -objects are those of the form R L for L a boolean locale ( P -locale). Finally, we show that a W -object G is pointwise σ -complete iff it is epicomplete. [ABSTRACT FROM AUTHOR]

Objective The majority of scales to measure family member distress in dementia are designed for community settings and do not capture the unique burdens of the nursing home (NH) environment. We report the psychometric properties of a new Family Distress in Advanced Dementia Scale for use in the NH setting. Design, Setting, Participants Cross-sectional questionnaire of 130 family member health care proxies of NH residents with advanced dementia in 31 Boston-area NHs. Methods Thirty-one initial items were evaluated, measuring the frequency over the past 3 months of sources of distress. Exploratory factor analysis identified domains of distress; Cronbach's alpha was computed for each domain. Associations between the domains and other measures were evaluated using Pearson correlation coefficients, including measures of depression (PHQ-9), satisfaction with care (Satisfaction with Care at the End-of-Life in Dementia [SWC-EOLD]), and caregiver burden (Zarit Burden Interview short version). Results Factor analysis suggested 3 domains: emotional distress (9 items), dementia preparedness (5 items), and NH relations (7 items). Cronbach's alpha coefficients were 0.82, 0.75, and 0.83 respectively. The PHQ-9 correlated most strongly with the emotional distress factor (r = 0.34), the SWC-EOWD correlated most strongly with the NH relations factor (r = 0.35), as did the Zarit Burden Scale (r = 0.50). Conclusions The Family Distress in Advanced Dementia Scale encompasses 3 domains of distress. This scale represents a much needed tool to assess distress among family members of NH residents with advanced dementia and provides a metric to evaluate interventions in the population. [ABSTRACT FROM AUTHOR]

In older patients, delirium after surgery is associated with long-term cognitive decline (LTCD). The neural substrates of this association are unclear. Neurodegenerative changes associated with dementia are possible contributors. We investigated the relationship between brain atrophy rates in Alzheimer's disease (AD) and cognitive aging signature regions from magnetic resonance imaging before and one year after surgery, LTCD assessed by the general cognitive performance (GCP) score over 6 years post-operatively, and delirium in 117 elective surgery patients without dementia (mean age = 76). The annual change in cortical thickness was 0.2(1.7) % (AD-signature p = 0.09) and 0.4(1.7) % (aging-signature p = 0.01). Greater atrophy was associated with LTCD (AD-signature: beta(CI) = 0.24(0.06–0.42) points of GCP/mm of cortical thickness; p < 0.01, aging-signature: beta(CI) = 0.55(0.07–1.03); p = 0.03). Atrophy rates were not significantly different between participants with and without delirium. We found an interaction with delirium severity in the association between atrophy and LTCD (AD-signature: beta(CI) = 0.04(0.00–0.08), p = 0.04; aging-signature: beta(CI) = 0.08(0.03–0.12), p < 0.01). The rate of cortical atrophy and severity of delirium are independent, synergistic factors determining postoperative cognitive decline in the elderly. • Postoperative delirium is an independent risk factor for dementia. • Cortical brain atrophy may represent a substrate of the link delirium-dementia. • Patients with more severe delirium and greater atrophy had faster cognitive decline. • Delirium and cortical atrophy increase the risk of postoperative cognitive decline. [ABSTRACT FROM AUTHOR]

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy characterized by fibro-fatty replacement of predominantly the right ventricle (Rv), which predisposes patients to life-threatening ventricular arrhythmias and usually slowly progressive ventricular dysfunction. The disease is inherited as an autosomal dominant trait with incomplete penetrance and variable expressivity. Increased appreciation of ARVD/C as a "disease of the desmosome" has fueled research into possible disease mechanisms, and insights into ARVD/C pathogenesis are rapidly advancing. Although ARVD/C is known to preferentially affect the RV, early and/or predominant left ventricular involvement is increasingly recognized. Diagnosis is made by combining multiple sources of diagnostic information as prescribed by the consensus-based Task Force criteria. Affected individuals typically present in the third to fifth decade of life with palpitations, lightheadedness, or syncope due to frequent ventricular ectopy or arrhythmias originating from the RV. However, disease expression is highly variable, even among subjects from the same family or those carrying the same mutation. since sudden cardiac death can be the first manifestation of the disease, optimizing the approach to early detection and risk stratification of ARVD/C is of utmost importance. This review will discuss the changing spectrum of ARVD/C based on recent advances in diagnosis, genetics, and improved understanding of disease pathophysiology. [ABSTRACT FROM AUTHOR]

A microscale combustion calorimeter (MCC) was modified to study gas phase combustion of polymers and flame-retardant plastics by adding carbon monoxide (CO) and carbon dioxide (CO 2 ) analyzers to the standard oxygen (O 2 ) analyzer. Experiments were conducted on 22 hydrocarbon, heteroatom and halogen-containing polymers of known composition over a wide range of combustion temperatures and oxygen concentrations. At high temperatures and excess oxygen when combustion was complete, the oxygen consumed (ΔO 2 ) and CO 2 produced by combustion of the pyrolysis gases were in quantitative agreement with theoretical values for all of these charring and non-charring polymers. At lower combustor temperatures, halogen-containing polymers exhibited significantly reduced fuel oxidation rates, as evidenced by a shift in maximum ΔO 2 , CO and CO 2 yields to much higher temperatures. [ABSTRACT FROM AUTHOR]

Cores MAR02-45 and MAR05-03 were raised from 68–69 m water depth on the SW Black Sea shelf and indicate transgression and submergence beneath several tens of metres of water before 11.0 cal ka. Those who postulate a Black Sea lowstand below − 100 m until the approximately 9.1 cal ka reconnection with the world ocean have suggested that sites like MAR02-45 and MAR05-03 must have been located in perched lakes on what is now the modern shelf. However, the silt- and clay-fraction mineralogy of samples from MAR02-45 provides no evidence for a shift in provenance at 9.1 cal ka, with earlier input from local rivers and later input from a broader region. Sedimentary abundances of Sc, Fe, Co, Ce, La, Th and Y also show no significant downcore trends. These elements likely reside in aluminosilicate mineral grains shed from terrestrial sources, so negligible downcore variation suggests long-term continuity in the composition of the detrital supply. More critically, the volume of pre-9.1 cal ka sediment around the MAR02-45 and MAR05-03 sites is > 25 times the expected yield from local rivers over a 5000 year period, so other more substantial sources are required. The predominant silt size of the recovered sediments, the configuration of late Holocene currents in the western Black Sea, and analogies with dispersal systems elsewhere suggest that the bulk of the fine-grained muds at these sites likely came from the Danube and Kamchiya drainage basins where thick deposits of unconsolidated Pleistocene loess have been strongly dissected. To reach core sites on the SW Black Sea shelf, this material must have been advected from the Danube and Kamchiya deltas by unobstructed marine currents. Only thin event beds (tempestites) of fine sand and silt in the lower part of cores MAR02-45 and MAR05-03 are interpreted to have a local source in the Strandja Mountains of Thrace. Comparison of the palynology of surface samples from the Danube Delta and its associated coastal lagoons with the pre-9.1 cal ka sediments of core MAR02-45 confirms that the hypothesis of deposition in a perched ancient lake is untenable. [ABSTRACT FROM AUTHOR]

This is the second of three articles on the topic of truncation as an operation on divisible abelian lattice-ordered groups, or simply ℓ -groups. This article uses the notation and terminology of the first article and assumes its results. In particular, we refer to an ℓ -group with truncation as a truncated ℓ -group, or simply a trunc, and denote the category of truncs with truncation homomorphisms by AT . Here we develop the analog for AT of Madden's pointfree representation for W , the category of archimedean ℓ -groups with designated order unit. More explicitly, for every archimedean trunc A there is a regular Lindelöf frame L equipped with a designated point ⁎ : L → 2 , a subtrunc A ˆ of R 0 L , the trunc of pointed frame maps O 0 R → L , and a trunc isomorphism A → A ˆ . A pointed frame map is just a frame map between frames which commutes with their designated points, and O 0 R stands for the pointed frame which is the topology O R of the real numbers equipped with the frame map of the insertion 0 → R . ( L , ⁎ ) is unique up to pointed frame isomorphism with respect to its properties. Finally, we reprove an important result from the first article, namely that W is a non-full monoreflective subcategory of AT . [ABSTRACT FROM AUTHOR]

As demand for mobile broadband services continues to explode, mobile wireless networks must expand greatly their capacities. This paper describes and quantifies the economic and technical challenges associated with deepening wireless networks to meet this growing demand. Methods of capacity expansion divide into three general categories: the deployment of more radio spectrum; more intensive geographic reuse of spectrum; and increasing the throughput capacity of each MHz of spectrum within a given geographic area. The paper describes these several basic methods to deepen mobile wireless capacity. It goes on to measure the contribution of each of these methods to historical capacity growth within U.S. networks. The paper then describes the capabilities of 4G LTE wireless technology, and further innovations off of it, to further improve network capacity. These capacity expansion capabilities of LTE-Advanced along with traditional spectrum reuse are quantified and compared to forecasts of future demand to evaluate the ability of U.S. networks to match future demand. Without significantly increasing current spectrum allocations by 560 MHz over the 2014–2022 period, the presented model suggests that U.S. wireless capacity expansion will be inadequate to accommodate expected demand growth. This conclusion is in contrast to claims that the U.S. faces no spectrum shortage. [ABSTRACT FROM AUTHOR]

Resistance to anti-estrogen therapies is a prominent challenge in the treatment of ovarian cancer. Tumors develop endocrine resistance by acquiring adaptations that help them rely on alternative oncogenic signaling cascades, which crosstalk with estrogen signaling pathways. An understanding of estrogen signaling crosstalk with these growth promoting cascades is essential in order to maximize efficacy of anti-estrogen treatments in ovarian cancer. Herein, we provide an overview of estrogen signaling in ovarian cancer and discuss the major challenges associated with anti-estrogen therapies. We also review what is currently known about how genomic and non-genomic estrogen signaling pathways crosstalk with several major oncogenic signaling cascades. The insights provided here illustrate existing strategies for targeting endocrine resistant ovarian tumors and may help identify new strategies to improve the treatment of this disease. [ABSTRACT FROM AUTHOR]

Prevalence of Type 2 diabetes has increased at an alarming rate, highlighting the need to correctly predict the development of this disease in order to allow intervention and thus, slow progression of the disease and resulting metabolic derangement. There have been many recent 'advances' geared toward the detection of pre-diabetes, including genome wide association studies and metabolomics. Although these approaches generate a large amount of data with a single blood sample, studies have indicated limited success using genetic and metabolomics information alone for identification of disease risk. Clinical assessment of the disposition index (DI), based on the hyperbolic law of glucose tolerance, is a powerful predictor of Type 2 diabetes, but is not easily assessed in the clinical setting. Thus, it is evident that combining genetic or metabolomic approaches for a more simple assessment of DI may provide a useful tool to identify those at highest risk for Type 2 diabetes, allowing for intervention and prevention. [ABSTRACT FROM AUTHOR]

The recent pig heart transplant in a patient at the University of Maryland Medical Center has stimulated renewed interest in the xenotransplantation of organs from genetically engineered pigs. The barriers to the use of pigs as sources of organs have largely been overcome by 2 approaches – (1) the deletion of expression of the three known pig carbohydrate xenoantigens against which humans have preformed antibodies, and (2) the transgenic introduction of human 'protective' proteins, such as complement-regulatory proteins. These gene modifications, coupled with immunosuppressive therapy based on blockade of the CD40/CD154 costimulation pathway, have resulted in survival of baboons with life-supporting pig heart grafts for almost 9 months. The initial clinical success at the University of Maryland reinforces encouraging preclinical results. It suggests that pig hearts are likely to provide an effective bridge to an allotransplant, but their utility for destination therapy remains uncertain. Because of additional complex immunobiological problems, the same approach has been less successful in preclinical lung xenograft transplantation, where survival is still measured in days or weeks. The first formal clinical trials of pig heart transplantation may include patients who do not have access to an allotransplant, those with contraindications for mechanical circulatory support, those in need of retransplantation or with a high level of panel-reactive antibodies. Infants with complex congenital heart disease, should also be considered. [ABSTRACT FROM AUTHOR]

Healthy aging is typically accompanied by cognitive decline. Previous work has shown that engaging in multiple, non-work activities during midlife can have a protective effect on cognition several decades later, rendering it less dependent on brain structural health; the definition of "cognitive reserve". Other work has shown that increasing age is associated with reduced segregation of large-scale brain functional networks. Here we tested the hypothesis that functional segregation (SyS) mediates this effect of middle-aged lifestyle on late-life cognition. We used fMRI data from three tasks in the CamCAN dataset, together with cognitive data on fluid intelligence, episodic memory, and retrospective lifestyle data from the Lifetime of Experiences Questionnaire (LEQ). In all three tasks, we showed that SyS related to fluid intelligence even after adjusting for the (nonlinear) age effects. However, we found no evidence that SyS in late-life mediated the relationship between non-specific (non-occupation) midlife activities and either measure of cognition in late-life. Thus, the brain correlates of cognitive reserve arising from mid-life activities remain to be discovered. • System segregation (SyS) is stable across different brain states. • SyS is negatively associated with age. • Fluid intelligence, but not episodic memory, was robustly predicted by SyS. • Late life SyS was not associated with midlife outside of work activities. [ABSTRACT FROM AUTHOR]

A key question in studies of cognitive development is whether bilingual environments impact higher-cognitive functions. Inconclusive evidence in search of a "bilingual cognitive advantage" has sparked debates on the reliability of these findings. Few studies with infants have examined this question, but most of them include small samples. The current study presents evidence from a large sample of 6- and 10-month-old monolingual- and bilingual-exposed infants (N = 152), which includes a longitudinal subset (n = 31), who completed a cueing attentional orienting task. The results suggest bilingual infants showed significant developmental gains in latency performance during the condition that was most cognitively demanding (Incongruent). The results also revealed bilingual infants' performance was associated with their parents' dual-language switching behavior. Taken together, these results provide support that bilingual experiences (i.e., dual-language mixing) influence infants' shifting and orienting of attention. [ABSTRACT FROM AUTHOR]

Abstract: Anthropogenically disturbed coastal acid sulfate soils along the east coast of Australia, and worldwide, periodically result in the discharge of acid waters containing high concentrations of metals. Identifying priority sites (hotspots) within a catchment for acid sulfate soil remediation activities typically involves long-term monitoring of drainwater chemistry, including the capture of data on unpredictable rain-induced groundwater discharge events. To improve upon this monitoring approach, this study investigated using the water lily (Nymphaea capensis) as a biomonitor of drainage waters to identify hotspots in three acid sulfate soil impacted catchments (83km2) in north-eastern New South Wales, Australia. In one catchment where the location of hotspots was known, water lily lamina concentrations of a suite of metal(loid)s were significantly (p< 0.05) higher than plants collected from an unpolluted ‘reference’ drainage channel, thus validating the concept of using this species as a biomonitor. A catchment-scale water lily sampling program undertaken in catchments with unidentified hotspots revealed within catchment variation of plant metal concentrations up to 70-fold. High resolution maps produced from these results, therefore, provided strong evidence for the location of potential hotspots which were confirmed with measurements of drainwater chemistry during rain-induced groundwater discharge events. Median catchment lily accumulation was ca. 160mgAlkg−1 and 1300mgFekg−1, with hotspots containing up to 6- and 10-fold higher Al and Fe concentrations. These findings suggest that biomonitoring with N. capensis can be an important tool to rapidly identify priority sites for remediation in acid sulfate soil impacted landscapes. [Copyright &y& Elsevier]

Highlights: [•] S–R bindings are more flexible and pervasive than previously thought. [•] S–R bindings can simultaneously encode multiple stimulus and response representations. [•] S–R bindings can be encoded or retrieved in the absence of attention or awareness. [•] S–R bindings complicate interpretations of priming, but are interesting in their own right. [•] S–R bindings enable rapid yet context-dependent behaviors. [ABSTRACT FROM AUTHOR]

Abstract: We prove that the category of unital hyperarchimedean vector lattices is equivalent to the category of Boolean algebras. The key result needed to establish the equivalence is that, via the Yosida representation, such a vector lattice is naturally isomorphic to the vector lattice of all locally constant real-valued continuous functions on a Boolean (= compact Hausdorff totally disconnected) space. We give two applications of our main result. [Copyright &y& Elsevier]

Abstract: The molecular mechanisms operating on a seasonal time-scale and regulating functions such as reproduction are poorly understood in animals living in desert environments. Kisspeptin, the product of the KiSS-1 gene, plays a critical role in control of the hypothalamic-pituitary-gonad axis that orchestrates the reproductive system in vertebrates. We report a sequence analysis of KiSS-1 and the pituitary luteinising hormone-beta (LHβ) and follicle-stimulating hormone-beta (FSHβ) in the Libyan jird (Meriones libycus), a seasonal breeding rodent that is sexually active during spring and quiescent in fall. We also assessed gene expression by quantitative real-time reverse transcription-polymerase chain reaction during the non-breeding and breeding seasons. The KiSS-1 cDNA sequence analysis showed high homology between M. libycus and all other rodents (94%) and humans (92%). KiSS-1 expression was higher during the breeding season than that during the non-breeding season. In contrast, LHβ and FSHβ expression levels were higher during the non-breeding season in autumn and varied in an opposite manner with testicular, seminal vesicle weights and plasma testosterone levels. Our results extend the role for KiSS-1 in activating the HPG axis in this desert rodent in its natural biotope by relaying environmental cues as in other seasonal non-desert rodent models. [Copyright &y& Elsevier]