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There has been strong interest recently in the so-called Cooper pair density wave, subsequent to the proposition that such a state occurs in the hole-doped cuprate superconductors. As of now, there is no convincing demonstration of such a state in the cuprate theoretical literature. We present here a brief but complete review of our theoretical and computational work on the paired-electron crystal (PEC), which has also been experimentally seen in the insulating phase proximate to superconductivity (SC) in organic charge-transfer solid (CTS) superconductors. Within our theory, SC in the CTS does indeed evolve from the PEC. A crucial requirement for the finding of the PEC is that the proper carrier density of one charge carrier per two sites is taken into consideration at the outset. Following the discussion of CTS superconductors, we briefly discuss how the theory can be extended to understand the phase diagram of the cuprate superconductors that has remained mysterious after nearly four decades of the discovery of SC in this family.

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The winter and summer monsoons in Southeast Asia are important but highly variable sources of rainfall. Current understanding of the winter monsoon is limited by conflicting proxy observations, resulting from the decoupling of regional atmospheric circulation patterns and local rainfall dynamics. These signals are difficult to decipher in paleoclimate reconstructions. Here, we present a winter monsoon speleothem record from Southeast Asia covering the Holocene and find that winter and summer rainfall changed synchronously, forced by changes in the Pacific and Indian Oceans. In contrast, regional atmospheric circulation shows an inverse relation between winter and summer controlled by seasonal insolation over the Northern Hemisphere. We show that disentangling the local and regional signal in paleoclimate reconstructions is crucial in understanding and projecting winter and summer monsoon variability in Southeast Asia.

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The timing and mechanisms of past hydroclimate change in northeast Mexico are poorly constrained, limiting our ability to evaluate climate model performance. To address this, we present a multiproxy speleothem record of past hydroclimate variability spanning 62.5 to 5.1 ka from Tamaulipas, Mexico. Here we show a strong influence of Atlantic and Pacific sea surface temperatures on orbital and millennial scale precipitation changes in the region. Multiple proxies show no clear response to insolation forcing, but strong evidence for dry conditions during Heinrich Stadials. While these trends are consistent with other records from across Mesoamerica and the Caribbean, the relative importance of thermodynamic and dynamic controls in driving this response is debated. An isotope-enabled climate model shows that cool Atlantic SSTs and stronger easterlies drive a strong inter-basin sea surface temperature gradient and a southward shift in moisture convergence, causing drying in this region.

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The Pacific cold tongue annual cycle in sea surface temperature is presumed to be driven by Earth's axial tilt1-5 (tilt effect), and thus its phasing should be fixed relative to the calendar. However, its phase and amplitude change dramatically and consistently under various configurations of orbital precession in several Earth System models. Here, we show that the cold tongue possesses another annual cycle driven by the variation in Earth-Sun distance (distance effect) from orbital eccentricity. As the two cycles possess slightly different periodicities6, their interference results in a complex evolution of the net seasonality over a precession cycle. The amplitude from the distance effect increases linearly with eccentricity and is comparable to the amplitude from the tilt effect for the largest eccentricity values over the last million years (e value approximately 0.05)7. Mechanistically, the distance effect on the cold tongue arises through a seasonal longitudinal shift in the Walker circulation and subsequent annual wind forcing on the tropical Pacific dynamic ocean-atmosphere system. The finding calls for reassessment of current understanding of the Pacific cold tongue annual cycle and re-evaluation of tropical Pacific palaeoclimate records for annual cycle phase changes.

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As the world warms, there is a profound need to improve projections of climate change. Although the latest Earth system models offer an unprecedented number of features, fundamental uncertainties continue to cloud our view of the future. Past climates provide the only opportunity to observe how the Earth system responds to high carbon dioxide, underlining a fundamental role for paleoclimatology in constraining future climate change. Here, we review the relevancy of paleoclimate information for climate prediction and discuss the prospects for emerging methodologies to further insights gained from past climates. Advances in proxy methods and interpretations pave the way for the use of past climates for model evaluation-a practice that we argue should be widely adopted.

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A major research question concerning global pelagic biodiversity remains unanswered: when did the apparent tropical biodiversity depression (i.e., bimodality of latitudinal diversity gradient [LDG]) begin? The bimodal LDG may be a consequence of recent ocean warming or of deep-time evolutionary speciation and extinction processes. Using rich fossil datasets of planktonic foraminifers, we show here that a unimodal (or only weakly bimodal) diversity gradient, with a plateau in the tropics, occurred during the last ice age and has since then developed into a bimodal gradient through species distribution shifts driven by postglacial ocean warming. The bimodal LDG likely emerged before the Anthropocene and industrialization, and perhaps ∼15,000 y ago, indicating a strong environmental control of tropical diversity even before the start of anthropogenic warming. However, our model projections suggest that future anthropogenic warming further diminishes tropical pelagic diversity to a level not seen in millions of years.

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Liver abscesses in feedlot cattle are detrimental to animal performance and economic return. Tylosin, a macrolide antibiotic, is used to reduce prevalence of liver abscesses, though there is variable efficacy among different groups of cattle. There is an increased importance in better understanding the etiology and pathogenesis of this condition because of growing concern over antibiotic resistance and increased scrutiny regarding use of antibiotics in food animal production. The objective of this study was to compare the microbiomes and antimicrobial resistance genes (resistomes) of feces of feedlot cattle administered or not administered tylosin and in their pen soil in 3 geographical regions with differing liver abscess prevalences. Cattle (total of 2,256) from 3 geographical regions were selected for inclusion based on dietary supplementation with tylosin (yes/no). Feces and pen soil samples were collected before harvest, and liver abscesses were identified at harvest. Shotgun and 16S rRNA amplicon sequencing were used to evaluate the soil and feces. Microbiome and resistome composition of feces (as compared by UniFrac distances and Euclidian distances, respectively) did not differ (P > 0.05) among tylosin or no tylosin-administered cattle. However, feedlot location was associated with differences (P ≤ 0.05) of resistomes and microbiomes. Using LASSO, a statistical model identified both fecal and soil microbial communities as predictive of liver abscess prevalence in pens. This model explained 75% of the variation in liver abscess prevalence, though a larger sample size would be needed to increase robustness of the model. These data suggest that tylosin exposure does not have a large impact on cattle resistomes or microbiomes, but instead, location of cattle production may be a stronger driver of both the resistome and microbiome composition of feces.

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OBJECTIVES: The purpose of this study was to evaluate the chiral stability of clopidogrel bisulfate in an extemporaneously compounded oral suspension for a period of 60 days. METHODS: A 5 mg/mL oral suspension of clopidogrel bisulfate was prepared from commercially available Plavix tablets. The clopidogrel suspension was then evenly divided between two light-resistant prescription bottles and stored either under refrigeration (4°C) or at room temperature (25°C). Samples were drawn from the stored suspensions immediately after preparation and on days 7, 14, 28, and 60. Samples were subsequently analyzed at each time point by high-performance liquid chromatography using a reversed-phase column, with chemical stability defined as the retention of at least 90% of the initial intact clopidogrel concentration measured. To determine the chiral stability of the suspension, samples were also analyzed by high-performance liquid chromatography using a chiral column to investigate possible enantiomeric inversion. Chiral stability was defined as the retention of at least 90% of the initial concentration of the suspension as the S-enantiomer, the active moiety of Plavix. RESULTS: Regardless of storage conditions, the oral suspension of clopidogrel retained at least 98% of the active S-enantiomer for 60 days after preparation. Compared with the clopidogrel suspension stored in the refrigerator, more chiral inversion was noted in the clopidogrel suspension stored at room temperature. CONCLUSIONS: Our investigation of chiral stability indicates that a 5 mg/mL clopidogrel oral suspension stored under refrigeration and at room temperature maintains chiral stability as the active S-enantiomer.

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A frustrated, effective ½-filled band Hubbard-Heisenberg model has been proposed for describing the strongly dimerized charge-transfer solid families κ-(ET)2X and Z[Pd(dmit)2]2. In addition to showing unconventional superconductivity, these materials also exhibit antiferromagnetism, candidate spin-liquid phases, and, in the case of Z=EtMe3P, a spin-gapped phase that has sometimes been referred to as a valence bond solid. We show that neither superconductivity nor the valence bond order phase occurs within the Hubbard-Heisenberg model. We suggest that a description based on »-filling, that is reached when the carrier concentration per molecule instead of per dimer is considered, thus may be appropriate.

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INTRODUCTION: Physicians are continually encouraged to be more productive while providing higher levels of patient satisfaction. It is a common presumption that the two goals are somewhat exclusive-that higher productivity must entail a sacrifice in patient satisfaction or vice versa. Moreover, physicians seeking tested, evidence-based approaches to improving satisfaction have had relatively little to go on, and they commonly have justifiable concerns about how ineffective changes may hurt their productivity for no benefit. METHODS: For our large specialty practice, we plotted physicians into quadrants on a scattergram: strong performers on productivity and patient satisfaction, those who are weak in both areas, and those who are strong in one and weak in the other. We performed an observational study to investigate behaviors and work processes associated with a range of performance levels in productivity and patient satisfaction. RESULTS: The observation yielded clear, discrete sets of common characteristics for physicians and staff in each quadrant. In our organization, these findings have provided practical assistance for physicians performing at any level to assess their own situation and chart a path, on their own or with coaching, that leads to improvement. CONCLUSIONS: The findings help dispel commonly held myths about the exclusivity of productivity and patient satisfaction, suggesting that 1) there are many physicians who excel in both areas simultaneously, and 2) there are different characteristics associated with varying levels of performance. The study encourages the further development of evidence-based methods for improving the patient experience while enhancing-not sacrificing-productivity.

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A natural explanation for the carrier concentration-dependent electronic behavior in the layered cobaltates emerges within correlated-electron Hamiltonians with finite on-site and significant nearest neighbor hole-hole Coulomb repulsions. The nearest neighbor repulsion decreases hole double occupancy below hole density 1/3, but increases the same at higher hole densities. Our conclusion is valid for both single-band and three-band extended Hubbard Hamiltonians, and sheds light on concentration dependent e'(g) hole occupancy within the latter.

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Recent case reports of acute pancreatitis in patients with type 2 diabetes (T2DM) treated with incretin-based therapies have triggered interest regarding the possibility of a mechanism-based association between pancreatitis and glucagon-like peptide-1 mimetics or dipeptidyl peptidase-4 (DPP-4) inhibitors. The objective of this review was to describe the controlled preclinical and clinical trial data regarding the incidence of pancreatitis with sitagliptin, the first DPP-4 inhibitor approved for use in patients with T2DM. Tissue samples from multiple animal species treated with sitagliptin for up to 2 years at plasma exposures substantially in excess of human exposure were evaluated to determine whether any potential gross or histomorphological changes suggestive of pancreatitis occurred. Sections were prepared by routine methods, stained with haematoxylin and eosin and examined microscopically. A pooled analysis of 19 controlled clinical trials, comprising 10,246 patients with T2DM treated for up to 2 years, was performed using patient-level data from each study for the evaluation of clinical and laboratory adverse events. Adverse events were encoded using the Medical Dictionary for Regulatory Activities (MedDRA) version 12.0 system. Incidences of adverse events were adjusted for patient exposure. Tissue samples from preclinical studies in multiple animal species did not reveal any evidence of treatment-related pancreatitis. The pooled analysis of controlled clinical trials revealed similar incidence rates of pancreatitis in patients treated with sitagliptin compared with those not treated with sitagliptin (0.08 events per 100 patient-years vs. 0.10 events per 100 patient-years, respectively). Preclinical and clinical trial data with sitagliptin to date do not indicate an increased risk of pancreatitis in patients with T2DM treated with sitagliptin.

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The competition between antiferromagnetic and spin-singlet ground states within quantum spin models and the ½-filled band Hubbard model has received intense scrutiny. Here we demonstrate a frustration-induced transition from Néel antiferromagnetism to a spin-singlet state in the interacting »-filled band on an anisotropic triangular lattice. While the antiferromagnetic state has equal charge densities, 0.5, on all sites, the spin-singlet state is a paired-electron crystal, with pairs of charge-rich sites separated by pairs of charge-poor sites. The paired-electron crystal provides a natural description of the spin-gapped state proximate to superconductivity in many organic charge transfer solids. Pressure-induced superconductivity in these correlated-electron systems is likely a result of a transition from the »-filled band valence bond solid to a valence bond liquid.

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Introdução: A escrita é instrumento e material importante para a construção de conhecimento de mundo e pode exercer papel fundamental no processo de desenvolvimento da linguagem de crianças e jovens com deficiência de audição. Objetivo: Discutir o processo de produção de textos de um jovem surdo. Material e método: Com base em um estudo de caso, foram consideradas as informações do histórico do caso, registros do processo terapêutico e o material produzido no atendimento realizado no Serviço de Audiologia Educacional da DERDIC - Divisão de Educação e Reabilitação dos Distúrbios da Comunicação. No método clínico, para a construção da memória discursiva, foram valorizados fatos ou acontecimentos trazidos à terapia espontaneamente ou relacionados à leitura de textos, bem como comentários e explicações que pudessem significar os temas abordados nas leituras e conversas que tivessem potencial para contribuir no processo de autoria e de estruturação da escrita de um livro. Resultados: Observou-se a partir deste caso que a prática discursiva: despertou a curiosidade sobre os recursos expressivos da escrita; deu textura às conversas produzidas; despertou prazer pela leitura e produção de textos bem como pelo diálogo oral; levou a uma relação mais criativa e partcipativa com conhecimento; desenvolveu maior autonomia discursiva. Conclusão: Com base neste estudo consideramos que a prática clínica fonoaudiológica estruturada no uso social da escrita pode alavancar o processo geral de desenvolvimento da linguagem.

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We report exact calculations of magnetic and superconducting pair-pair correlations for the half-filled band Hubbard model on an anisotropic triangular lattice. Our results for the magnetic phases are similar to those obtained with other techniques. The superconducting pair-pair correlations at distances beyond nearest neighbor decrease monotonically with increasing Hubbard interaction U for all anisotropy, indicating the absence of frustration-driven superconductivity within the model.

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OBJECTIVE: To evaluate development of components of polycystic ovary syndrome (PCOS) and PCOS in women with epilepsy initiating valproate or lamotrigine therapy. METHODS: Female individuals with epilepsy and regular menstrual cycles were eligible for this prospective study. Participants were randomized to 12 months of valproate (n = 225) or lamotrigine (n = 222) therapy. Serum androgen levels were measured every 3 months. Urinary pregnanediol glucuronide levels were measured weekly for two 3-month periods. The primary end point was development of PCOS components (ie, hyperandrogenism or ovulatory dysfunction). A post hoc analysis was conducted in women more than 2 years after menarche (177 lamotrigine, (HA) 186 valproate) to exclude OD the confounding effect of puberty. RESULTS: More women in the valproate group than the lamotrigine group developed (OD) in the prospective (54% valproate, 38% lamotrigine; p = 0.010) and the post hoc (HA) analyses (36% valproate, 23% lamotrigine; p = 0.007). More women in the valproate group than the lamotrigine group developed PCOS (9 vs 2%; p = 0.007). Development of HA was more frequent with OD valproate than lamotrigine among those initiating treatment at age younger than 26 years (44% valproate, 23% lamotrigine; p = 0.002) but was similar if treatment was started at age 26 years or older (24% valproate, 22% lamotrigine). INTERPRETATION: Development of HA occurred more frequently with valproate than lamotrigine, especially if medication was started at age younger than 26 years.

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This open-label study was designed to evaluate the long-term tolerability and efficacy of lamotrigine in 1- to 24-month-old infants with partial seizures. The study enrolled both lamotrigine-naïve patients and patients who had been previously exposed to lamotrigine in a randomized, double-blind, placebo-controlled study. Patients (n = 204) received lamotrigine according to a dosing schedule that depended on prior experience with lamotrigine and concurrent antiepileptic drug therapy for up to 48 weeks or their second birthday, whichever occurred last. Total duration of lamotrigine exposure (which included exposure during the placebo-controlled study in lamotrigine-experienced patients) was >/=24 weeks in 92% of patients, >/=48 weeks in 70% of patients, and >/=72 weeks in 20% of patients. A total of 20 (10%) patients (8 lamotrigine-naïve patients and 12 lamotrigine-experienced patients) transitioned to lamotrigine monotherapy. The most common adverse events were pyrexia (45% of patients), upper-respiratory tract infection (28%), and ear infection (22%). The only adverse event considered reasonably attributable to study medication in >2% of patients was irritability (n = 10; 5% of patients). No cases of serious rash were reported. The median percent reduction from baseline in partial seizure frequency in the sample as a whole was 74%. Seizure frequency was reduced by >/=50% from pre-lamotrigine baseline in 62% of patients in the sample as a whole, 60% of the lamotrigine-naïve subgroup, and 63% of the lamotrigine-experienced subgroup. In the sample as a whole, 13% of patients were seizure free during the Treatment Phase. Investigators considered clinical status at the last clinic visit to be improved (mildly, moderately, or markedly) relative to prelamotrigine clinical status in 76% of patients (150/197) and to be unchanged in 19% (37/197). In this study-the first large prospective investigation of the long-term tolerability and efficacy of an antiepileptic drug in a patient population 2 years and younger-lamotrigine administered for up to approximately 72 weeks was well tolerated and associated with good seizure control.

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We present a numerical study of the Hubbard-Holstein model in one dimension at half filling, including finite-frequency quantum phonons. At half filling, the effects of the electron-phonon and electron-electron interactions compete with the Holstein phonon coupling acting as an effective negative Hubbard on-site interaction U that promotes on-site electron pairs and a Peierls charge-density wave state. Most previous work on this model has assumed that only Peierls or Mott phases are possible at half filling. However, there has been speculation that a third metallic phase exists between the Peierls and Mott phases. We confirm the intermediate phase, and show that the Luttinger liquid correlation exponent K(rho) >1 in this region, indicating dominant superconducting pair correlations. We explore the full phase diagram as a function of Hubbard U, phonon coupling constant, and phonon frequency.

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PURPOSE: The purpose of the study was to evaluate the angiographic findings and results of embolotherapy in the management of lumbar artery trauma. METHODS: All patients with lumbar artery injury who underwent angiography and percutaneous embolization in a state trauma center within a 10-year period were retrospectively reviewed. Radiological information and procedural reports were reviewed to assess immediate angiographic findings and embolization results. Long-term clinical outcome was obtained by communication with the trauma physicians as well as with chart review. RESULTS: In a 10-year period, 255 trauma patients underwent abdominal aortography. Eleven of these patients (three women and eight men) suffered a lumbar artery injury. Angiography demonstrated active extravasation (in nine) and/or pseudoaneurysm (in four). Successful selective embolization of abnormal vessel(s) was performed in all patients. Coils were used in six patients, particles in one and gelfoam in five patients. Complications included one retroperitoneal abscess, which was treated successfully. One patient returned for embolization of an adjacent lumbar artery due to late pseudoaneurysm formation. CONCLUSIONS: In hemodynamically stable patients, selective embolization is a safe and effective method for immediate control of active extravasation, as well as to prevent future hemorrhage from an injured lumbar artery.

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