bluuebunny/crossref_metadata_2025 huggingface dataset:
History of the Treatment of Female Sexual Dysfunction(s)
Authors: Kleinplatz Peggy J.
Published: January 2018

This article reviews the history of the treatment of women's sexual problems from the Victorian era to the twenty-first century. The contextual nature of determining what constitutes female sexual psychopathology is highlighted. Conceptions of normal sexuality are subject to cultural vagaries, making it difficult to identify female sexual dysfunctions. A survey of the inclusion, removal, and collapsing of women's sexual diagnoses in the Diagnostic and Statistical Manual of Mental Disorders from 1952 to 2013 illuminates the biases in the various editions. Masters and Johnson's models of sexual response and dysfunction paved the way for the diagnosis and treatment of women's sexual dysfunctions. Their sex therapy paradigm is described. Conceptions of and treatments for anorgasmia, arousal difficulties, vaginismus, dyspareunia, and low desire are reviewed. The medicalization of human sexuality and the splintering of sex therapy are discussed, along with current trends and new directions in sexual health care for women.
CCR5 Governs DNA Damage Repair and Breast Cancer Stem Cell Expansion
Authors: Jiao Xuanmao , Velasco-Velázquez Marco A. , Wang Min , Li Zhiping , Rui Hallgeir , Peck Amy R. , Korkola James E. , Chen Xuelian , Xu Shaohua , DuHadaway James B. , Guerrero-Rodriguez Sandra , Addya Sankar , Sicoli Daniela , Mu Zhaomei , Zhang Gang , Stucky Andres , Zhang Xi , Cristofanilli Massimo , Fatatis Alessandro , Gray Joe W. , Zhong Jiang F. , Prendergast George C. , Pestell Richard G.
Published: January 2018

The functional significance of the chemokine receptor CCR5 in human breast cancer epithelial cells is poorly understood. Here, we report that CCR5 expression in human breast cancer correlates with poor outcome. CCR5+ breast cancer epithelial cells formed mammospheres and initiated tumors with >60-fold greater efficiency in mice. Reintroduction of CCR5 expression into CCR5-negative breast cancer cells promoted tumor metastases and induced DNA repair gene expression and activity. CCR5 antagonists Maraviroc and Vicriviroc dramatically enhanced cell killing mediated by DNA-damaging chemotherapeutic agents. Single-cell analysis revealed CCR5 governs PI3K/Akt, ribosomal biogenesis, and cell survival signaling. As CCR5 augments DNA repair and is reexpressed selectively on cancerous, but not normal breast epithelial cells, CCR5 inhibitors may enhance the tumor-specific activities of DNA damage response–based treatments, allowing a dose reduction of standard chemotherapy and radiation.

Significance: This study offers a preclinical rationale to reposition CCR5 inhibitors to improve the treatment of breast cancer, based on their ability to enhance the tumor-specific activities of DNA-damaging chemotherapies administered in that disease. Cancer Res; 78(7); 1657–71. ©2018 AACR.
2-Hydroxyglutarate-Mediated Autophagy of the Endoplasmic Reticulum Leads to an Unusual Downregulation of Phospholipid Biosynthesis in Mutant IDH1 Gliomas
Authors: Viswanath Pavithra , Radoul Marina , Izquierdo-Garcia Jose Luis , Ong Wei Qiang , Luchman Hema Artee , Cairncross J. Gregory , Huang Bo , Pieper Russell O. , Phillips Joanna J. , Ronen Sabrina M.
Published: January 2018

Tumor metabolism is reprogrammed to meet the demands of proliferating cancer cells. In particular, cancer cells upregulate synthesis of the membrane phospholipids phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdE) in order to allow for rapid membrane turnover. Nonetheless, we show here that, in mutant isocitrate dehydrogenase 1 (IDHmut) gliomas, which produce the oncometabolite 2-hydroxyglutarate (2-HG), PtdCho and PtdE biosynthesis is downregulated and results in lower levels of both phospholipids when compared with wild-type IDH1 cells. 2-HG inhibited collagen-4-prolyl hydroxylase activity, leading to accumulation of misfolded procollagen-IV in the endoplasmic reticulum (ER) of both genetically engineered and patient-derived IDHmut glioma models. The resulting ER stress triggered increased expression of FAM134b, which mediated autophagic degradation of the ER (ER-phagy) and a reduction in the ER area. Because the ER is the site of phospholipid synthesis, ER-phagy led to reduced PtdCho and PtdE biosynthesis. Inhibition of ER-phagy via pharmacological or molecular approaches restored phospholipid biosynthesis in IDHmut glioma cells, triggered apoptotic cell death, inhibited tumor growth, and prolonged the survival of orthotopic IDHmut glioma-bearing mice, pointing to a potential therapeutic opportunity. Glioma patient biopsies also exhibited increased ER-phagy and downregulation of PtdCho and PtdE levels in IDHmut samples compared with wild-type, clinically validating our observations. Collectively, this study provides detailed and clinically relevant insights into the functional link between oncometabolite-driven ER-phagy and phospholipid biosynthesis in IDHmut gliomas.

Significance: Downregulation of phospholipid biosynthesis via ER-phagy is essential for proliferation and clonogenicity of mutant IDH1 gliomas, a finding with immediate therapeutic implications. Cancer Res; 78(9); 2290–304. ©2018 AACR.
Safety, Activity, and Biomarkers of SHR-1210, an Anti-PD-1 Antibody, for Patients with Advanced Esophageal Carcinoma
Authors: Huang Jing , Xu Binghe , Mo Hongnan , Zhang Weilong , Chen Xuelian , Wu Dawei , Qu Dong , Wang Xingyuan , Lan Bo , Yang Beibei , Wang Pei , Zhang Hongtu , Yang Qing , Jiao Yuchen
Published: January 2018

Purpose: The current management of advanced esophageal squamous cell carcinoma (ESCC) remains unsatisfactory. We investigated the safety, efficacy, and biomarkers of SHR-1210, an anti-PD-1 antibody, in patients with recurrent or metastatic ESCC.

Experimental Design: This study was part of a phase I trial in China. Patients with advanced ESCC who were refractory or intolerant to previous chemotherapy were enrolled. Eligible patients received intravenous SHR-1210 at a dose of 60 mg, with escalation to 200 and 400 mg (4-week interval after first dose followed by a 2-week schedule) until disease progression or intolerable toxicity. The associations between candidate biomarkers (PD-L1 and somatic mutation load) and the efficacy of SHR-1210 were also explored.

Results: Between May 11, 2016, and December 9, 2016, a total of 30 patients from one site in China were enrolled. Ten patients (33.3%) had an independently assessed objective response. Median progression-free survival was 3.6 months (95% CI, 0–7.2). Three (10.0%) treatment-related grade 3 adverse events were reported: two (6.7%) pneumonitis and one (3.3%) increased cardiac troponin I. No grade 4 or grade 5 treatment-related adverse events were reported. The exome sequencing and analysis showed that the mutational burden and the potential mutation-associated neoantigen count were associated with better responses. An objective response was more common in patients with PD-L1–positive tumors as defined by ≥5% staining (7 of 15 patients) than in those with PD-L1–negative tumors (1 of 9 patients).

Conclusions: In this population of ESCC patients, SHR-1210 had a manageable safety profile and promising antitumor activity. Clin Cancer Res; 24(6); 1296–304. ©2018 AACR.
Beyond Concurrent Chemoradiation: The Emerging Role of PD-1/PD-L1 Inhibitors in Stage III Lung Cancer
Authors: McCall Neal S. , Dicker Adam P. , Lu Bo
Published: January 2018

Concurrent chemoradiation (cCRT) with platinum-based chemotherapy is standard-of-care therapy for patients with stage III unresectable non–small cell lung cancer (NSCLC). Although cCRT is potentially curative, 5-year overall survival has hovered around 20%, despite extensive efforts to improve outcomes with increasing doses of conformal radiation and intensification of systemic therapy with either induction or consolidation chemotherapy. PD-1/PD-L1 immune checkpoint inhibitors have demonstrated unprecedented efficacy in patients with stage IV NSCLC. In addition, preclinical and early clinical evidence suggests that chemotherapy and radiation may work synergistically with anti-PD-1/PD-L1 therapy to promote antitumor immunity, which has led to the initiation of clinical trials testing these drugs in patients with stage III NSCLC. A preliminary report of a randomized phase III trial, the PACIFIC trial, demonstrated an impressive increase in median progression-free survival with consolidative durvalumab, a PD-L1 inhibitor, compared with observation after cCRT. Here, we discuss the clinical and translational implications of integrating PD-1/PD-L1 inhibitors in the management of patients with unresectable stage III NSCLC. Clin Cancer Res; 24(6); 1271–6. ©2018 AACR.
Pembrolizumab Plus Pegylated Interferon alfa-2b or Ipilimumab for Advanced Melanoma or Renal Cell Carcinoma: Dose-Finding Results from the Phase Ib KEYNOTE-029 Study
Authors: Atkins Michael B. , Hodi F. Stephen , Thompson John A. , McDermott David F. , Hwu Wen-Jen , Lawrence Donald P. , Dawson Nancy A. , Wong Deborah J. , Bhatia Shailender , James Marihella , Jain Lokesh , Robey Seth , Shu Xinxin , Homet Moreno Blanca , Perini Rodolfo F. , Choueiri Toni K. , Ribas Antoni
Published: January 2018

Purpose: Pembrolizumab monotherapy, ipilimumab monotherapy, and pegylated interferon alfa-2b (PEG-IFN) monotherapy are active against melanoma and renal cell carcinoma (RCC). We explored the safety and preliminary antitumor activity of pembrolizumab combined with either ipilimumab or PEG-IFN in patients with advanced melanoma or RCC.

Experimental Design: The phase Ib KEYNOTE-029 study (ClinicalTrials.gov, NCT02089685) included independent pembrolizumab plus reduced-dose ipilimumab and pembrolizumab plus PEG-IFN cohorts. Pembrolizumab 2 mg/kg every 3 weeks (Q3W) plus 4 doses of ipilimumab 1 mg/kg Q3W was tolerable if ≤6 of 18 patients experienced a dose-limiting toxicity (DLT). The target DLT rate for pembrolizumab 2 mg/kg Q3W plus PEG-IFN was 30%, with a maximum of 14 patients per dose level. Response was assessed per RECIST v1.1 by central review.

Results: The ipilimumab cohort enrolled 22 patients, including 19 evaluable for DLTs. Six patients experienced ≥1 DLT. Grade 3 to 4 treatment-related adverse events occurred in 13 (59%) patients. Responses occurred in 5 of 12 (42%) patients with melanoma and 3 of 10 (30%) patients with RCC. In the PEG-IFN cohort, DLTs occurred in 2 of 14 (14%) patients treated at dose level 1 (PEG-IFN 1 μg/kg/week) and 2 of 3 (67%) patients treated at dose level 2 (PEG-IFN 2 μg/kg/week). Grade 3 to 4 treatment-related adverse events occurred in 10 of 17 (59%) patients. Responses occurred in 1 of 5 (20%) patients with melanoma and 2 of 12 (17%) patients with RCC.

Conclusions: Pembrolizumab 2 mg/kg Q3W plus ipilimumab 1 mg/kg Q3W was tolerable and provided promising antitumor activity in patients with advanced melanoma or RCC. The maximum tolerated dose of pembrolizumab plus PEG-IFN had limited antitumor activity in this population. Clin Cancer Res; 24(8); 1805–15. ©2018 AACR.
Molecular Genetic Mechanisms of Hereditary Spherocytosis: Current Perspectives
Authors: He Ben-Jin , Liao Lin , Deng Zeng-Fu , Tao Yi-Feng , Xu Yu-Chan , Lin Fa-Quan
Published: January 2018

With the widespread use of genetic diagnostic technologies, many novel mutations have been identified in hereditary spherocytosis (HS)-related genes, including SPTA1, SPTB, ANK1, SLC4A1, and EPB42. However, mutations in HS-related genes are dispersed and nonspecific in the diagnosis of some HS patients, indicating significant heterogeneity in the molecular deficiency of HS. It is necessary to provide the molecular and genetic characteristics of these 5 genes for clinicians to examine HS. Here, we reviewed the recent proposed molecular genetic mechanisms of HS.
Inflammatory Pathways Regulated by Tumor Necrosis Receptor–Associated Factor 1 Protect From Metabolic Consequences in Diet-Induced Obesity
Authors: Anto Michel Nathaly , Colberg Christian , Buscher Konrad , Sommer Björn , Pramod Akula Bala , Ehinger Erik , Dufner Bianca , Hoppe Natalie , Pfeiffer Katharina , Marchini Timoteo , Willecke Florian , Stachon Peter , Hilgendorf Ingo , Heidt Timo , von zur Muhlen Constantin , von Elverfeldt Dominik , Pfeifer Dietmar , Schüle Roland , Kintscher Ulrich , Brachs Sebastian , Ley Klaus , Bode Christoph , Zirlik Andreas , Wolf Dennis
Published: January 2018

Rationale:

The coincidence of inflammation and metabolic derangements in obese adipose tissue has sparked the concept of met-inflammation. Previous observations, however, suggest that inflammatory pathways may not ultimately cause dysmetabolism.

Objective:

We have revisited the relationship between inflammation and metabolism by testing the role of TRAF (tumor necrosis receptor–associated factor)-1, an inhibitory adapter of inflammatory signaling of TNF (tumor necrosis factor)-α, IL (interleukin)-1β, and TLRs (toll-like receptors).

Methods and Results:

Mice deficient for TRAF-1, which is expressed in obese adipocytes and adipose tissue lymphocytes, caused an expected hyperinflammatory phenotype in adipose tissue with enhanced adipokine and chemokine expression, increased leukocyte accumulation, and potentiated proinflammatory signaling in macrophages and adipocytes in a mouse model of diet-induced obesity. Unexpectedly, TRAF-1
−/−
mice were protected from metabolic derangements and adipocyte growth, failed to gain weight, and showed improved insulin resistance—an effect caused by increased lipid breakdown in adipocytes and UCP (uncoupling protein)-1–enabled thermogenesis. TRAF-1–dependent catabolic and proinflammatory cues were synergistically driven by β3-adrenergic and inflammatory signaling and required the presence of both TRAF-1–deficient adipocytes and macrophages. In human obesity, TRAF-1–dependent genes were upregulated.

Conclusions:

Enhancing TRAF-1–dependent inflammatory pathways in a gain-of-function approach protected from metabolic derangements in diet-induced obesity. These findings identify TRAF-1 as a regulator of dysmetabolism in mice and humans and question the pathogenic role of chronic inflammation in metabolism.
Surrogate Markers of Cardiovascular Risk and Chronic Obstructive Pulmonary Disease
Authors: Fisk Marie , McEniery Carmel M. , Gale Nichola , Mäki-Petäjä Kaisa , Forman Julia R. , Munnery Margaret , Woodcock-Smith Jean , Cheriyan Joseph , Mohan Divya , Fuld Jonathan , Tal-Singer Ruth , Polkey Michael I. , Cockcroft John R. , Wilkinson Ian B. , Bolton Charlotte , Calverley Peter , Lomas David , MacNee William , Marchong Mellone , Miller Bruce , Nagarajan Sridevi , Dhakam Zahid , Hickson Stacey , Howard Julia , McDonnell Barry , Miles Karen , Munnery Maggie , Pusalkar Pawan , Retallick Christopher , Smith Jane , Thomas Edna , Wallace Sharon , Williams Susannah , Yasmin
Published: January 2018

Cardiovascular disease is a common comorbidity and cause of mortality in chronic obstructive pulmonary disease. A better understanding of mechanisms of cardiovascular risk in chronic obstructive pulmonary disease patients is needed to improve clinical outcomes. We hypothesized that such patients have increased arterial stiffness, wave reflections, and subclinical atherosclerosis compared with controls and that these findings would be independent of smoking status and other confounding factors. A total of 458 patients with a diagnosis of chronic obstructive pulmonary disease and 1657 controls (43% were current or ex-smokers) with no airflow limitation were matched for age, sex, and body mass index. All individuals underwent assessments of carotid–femoral (aortic) pulse wave velocity, augmentation index, and carotid intima–media thickness. The mean age of the cohort was 67±8 years and 58% were men. Patients with chronic obstructive pulmonary disease had increased aortic pulse wave velocity (9.95±2.54 versus 9.27±2.41 m/s;
P
<0.001), augmentation index (28±10% versus 25±10%;
P
<0.001), and carotid intima–media thickness (0.83±0.19 versus 0.74±0.14 mm;
P
<0.001) compared with controls. Chronic obstructive pulmonary disease was associated with increased levels of each vascular biomarker independently of physiological confounders, smoking, and other cardiovascular risk factors. In this large case-controlled study, chronic obstructive pulmonary disease was associated with increased arterial stiffness, wave reflections, and subclinical atherosclerosis, independently of traditional cardiovascular risk factors. These findings suggest that the cardiovascular burden observed in this condition may be mediated through these mechanisms and supports the concept that chronic obstructive pulmonary disease is an independent risk factor for cardiovascular disease.
A new species of Puddle Frog, genus Phrynobatrachus (Amphibia: Anura: Phrynobatrachidae) from Ghana
Authors: OFORI-BOATENG CALEB , LEACHÉ ADAM D. , OBENG-KANKAM BRIGHT , KOUAMÉ N’GORAN GERMAIN , HILLERS ANNIKA , RÖDEL MARK-OLIVER
Published: January 2018

We describe a new species of Phrynobatrachus from the eastern part of the Upper Guinea forest region, Ghana, West Africa. Morphologically, the new species can be distinguished from all of its congeners by the combination of a slender body, short and pointed snout, a relatively warty dorsum, a black-spotted throat in both sexes, a gular flap in males, a dark spotted chest, a white-greyish venter with occasional blackish spots, rudimentary pedal webbing, none to slightly dilated finger tips and strongly delated toe tips, presence of both inner and outer metatarsal tubercles and absence of a dark face mask, eyelid tubercles and longer dorsal ridges. We collected mitochondrial DNA (mtDNA) sequence data from the 16S rRNA gene to measure the genetic diversity of the new species, and to estimate phylogenetic relationships. The new species is a distinct and monophyletic evolutionary lineage most closely related to Phrynobatrachus gutturosus, P. fraterculus and P. maculiventris. The discovery of this new species highlights that the biodiversity of West African forests is still incompletely known and that the few remaining forests need urgent protection.
The Sky in Edvard Munch’s The Scream
Authors: Prata Fred , Robock Alan , Hamblyn Richard
Published: January 2018

The Scream is a well-known painting by Edvard Munch (1863–1944). The Norwegian word used by Munch is “skrik,” which can be translated as “shriek” or “scream.” The Scream may be of interest to meteorologists because of the quite striking representation of the sky. It has been suggested that the dramatic red-colored sky was inspired by a volcanic sunset seen by Munch after the Krakatau eruption in 1883 and by a sighting of stratospheric nacreous clouds, and also that it is part of the artist’s expression of a scream from nature. The evidence for the volcanic sunset theory and Munch’s psyche are briefly reviewed. We provide support that Munch’s inspiration may have been from a sighting of nacreous clouds, observable from southern Norway during the winter months. We show that the colors and patterns of the sky in Munch’s painting match the sunset colors better if nacreous clouds are present. Their sudden appearance around and after sunset creates an impressive and dramatic effect. By comparing the color content of photographs and paintings of regular sunsets, volcanic sunsets, and nacreous clouds after sunset with the color content of the sky in The Scream, the match is better with nacreous clouds present. If this conjecture is correct, then Munch’s sky in The Scream represents one of the earliest visual documentations of a nacreous cloud display.
Precipitation Susceptibility and Aerosol Buffering of Warm- and Mixed-Phase Orographic Clouds in Idealized Simulations
Authors: Glassmeier Franziska , Lohmann Ulrike
Published: January 2018

The sensitivity of warm- and mixed-phase orographic precipitation to the aerosol background with simultaneous changes in the abundance of cloud condensation nuclei and ice nucleating particles is explored in an idealized, two-dimensional modeling study. The concept of precipitation susceptibility dlnP/dlnN, where P is the precipitation mixing ratio and N the cloud droplet number, is adapted for orographic clouds. Precipitation susceptibility is found to be low because perturbations to different precipitation formation pathways compensate each other. For mixed-phase conditions, this in particular means a redistribution between warm and cold pathways. The compensating behavior is described as a consequence of a balance equation for the cloud water along parcel trajectories that constrains the total precipitation formation to match the drying from condensation and vapor deposition on ice-phase hydrometeors caused by the mountain flow. For an aerosol-independent condensation rate (saturation adjustment), this balance requirement limits aerosol impacts on orographic precipitation (i) to the evaporation of hydrometeors and (ii) to the glaciation state of the cloud, which controls the contribution of vapor deposition to drying. The redistribution of precipitation formation pathways is coupled to a redistribution of the total hydrometeor mass between hydrometeor categories. Aerosol effects on the glaciation state of the cloud enhance this redistribution effect such that liquid and ice adjustments do not compensate. For the externally constrained, fully adjusted steady-state situation studied, precipitation susceptibility quantifies the redistribution effect rather than changes in precipitation production as in previous studies.
Toward Predicting Changes in the Land Monsoon Rainfall a Decade in Advance
Authors: Wang Bin , Li Juan , Cane Mark A. , Liu Jian , Webster Peter J. , Xiang Baoqiang , Kim Hye-Mi , Cao Jian , Ha Kyung-Ja
Published: January 2018

Predictions of changes of the land monsoon rainfall (LMR) in the coming decades are of vital importance for successful sustainable economic development. Current dynamic models, though, have shown little skill in the decadal prediction of the Northern Hemisphere (NH) LMR (NHLMR). The physical basis and predictability for such predictions remain largely unexplored. Decadal change of the NHLMR reflects changes in the total NH continental precipitation, tropical general circulation, and regional land monsoon rainfall over northern Africa, India, East Asia, and North America. Using observations from 1901 to 2014 and numerical experiments, it is shown that the decadal variability of the NHLMR is rooted primarily in (i) the north–south hemispheric thermal contrast in the Atlantic–Indian Ocean sector measured by the North Atlantic–south Indian Ocean dipole (NAID) sea surface temperature (SST) index and (ii) an east–west thermal contrast in the Pacific measured by an extended El Niño–Southern Oscillation (XEN) index. Results from a 500-yr preindustrial control experiment demonstrate that the leading mode of decadal NHLMR and the associated NAID and XEN SST anomalies may be largely an internal mode of Earth’s climate system, although possibly modified by natural and anthropogenic external forcing. A 51-yr, independent forward-rolling decadal hindcast was made with a hybrid dynamic conceptual model and using the NAID index predicted by a multiclimate model ensemble. The results demonstrate that the decadal changes in the NHLMR can be predicted approximately a decade in advance with significant skills, opening a promising way forward for decadal predictions of regional land monsoon rainfall worldwide.
Atmospheric Patterns over the Antarctic Peninsula
Authors: Gonzalez Sergi , Vasallo Francisco , Recio-Blitz Cayetana , Guijarro José A. , Riesco Jesús
Published: January 2018

Using clustering analysis for the sea level pressure field of the ERA-Interim reanalysis between 1979 and 2016, five synoptic pressure patterns have been obtained for the Drake area and Antarctic Peninsula (AP) region (45°–75°S, 20°–120°W), and the resulting daily series has been made available to the scientific community. The five patterns have been named according to their most important features as follows: low over the Weddell Sea (LWS), low over the Amundsen and Bellingshausen Seas (LAB), low over the Drake Passage (LDP), zonal flow over the Drake Passage (ZDP), and ridge over the Antarctic Peninsula (RAP). Each atmospheric pattern is described after analyzing its development and evolution. A frequency analysis shows that the five atmospheric patterns present a similar annual frequency but a large seasonal variability. The transitions from one pattern to another tend to follow a cycle in which synoptic atmospheric waves are displaced eastward by a quarter wavelength. Four of the five atmospheric patterns (all except RAP) are very influenced by the southern annular mode (SAM); however, only LAB and LWS are influenced to some degree by ENSO. The occurrence of the LAB pattern presents a positive trend showing agreement with other studies that indicate an enhancement of the Amundsen–Bellingshausen Seas low. Finally, atmospheric circulation patterns have been related to the airmass advection and precipitation in Livingston Island, showing the potential application for studying the changes in the surface mass balance on the AP cryosphere.
Optimizing the Definition of a Sudden Stratospheric Warming
Authors: Butler Amy H. , Gerber Edwin P.
Published: January 2018

Various criteria exist for determining the occurrence of a major sudden stratospheric warming (SSW), but the most common is based on the reversal of the climatological westerly zonal-mean zonal winds at 60° latitude and 10 hPa in the winter stratosphere. This definition was established at a time when observations of the stratosphere were sparse. Given greater access to data in the satellite era, a systematic analysis of the optimal parameters of latitude, altitude, and threshold for the wind reversal is now possible. Here, the frequency of SSWs, the strength of the wave forcing associated with the events, changes in stratospheric temperature and zonal winds, and surface impacts are examined as a function of the stratospheric wind reversal parameters. The results provide a methodical assessment of how to best define a standard metric for major SSWs. While the continuum nature of stratospheric variability makes it difficult to identify a decisively optimal threshold, there is a relatively narrow envelope of thresholds that work well—and the original focus at 60° latitude and 10 hPa lies within this window.
The Time Delay of Flow and Sediment in the Middle and Lower Yangtze River and Its Response to the Three Gorges Dam
Authors: Li Yangyang , Zhu Yingxin , Chen Lei , Shen Zhenyao
Published: January 2018

As the largest hydropower project in the world, the Three Gorges Dam (TGD) has drawn extensive concern in terms of its impact on downstream areas. In this study, an improved time delay estimation and wavelet analysis were used to investigate the influence of the TGD on the streamflow and sediment in the middle and lower Yangtze River, using time series of the daily discharge and sediment concentration data from three hydrological stations downstream of the dam. The results indicated that all of the time series at the three stations have prominent annual cycles, but the cycle of daily mean sediment concentration was nearly nonexistent after the impoundment of the TGD. Changes in discharge and sediment between the Yichang and the Hankou stations are larger than those between the Hankou and the Datong stations, which is mainly attributed to the streamflows of tributaries and Dongting Lake and the flood diversion area of Jingjiang. The transmission time of discharge for the whole Yichang–Datong river section is approximately 6 days. In addition, the attenuation of discharge from the Yichang station to the Datong station is 20%–30%. In contrast, the transmission of suspended sediment is slower than that of discharge, which takes 7–7.5 days to move from the Yichang station to the Datong station. The attenuation of sediment is approximately 30% in the Yichang–Datong river section and shows a clear increasing trend after 2006, mainly because a large amount of sediment was trapped by the TGD, and the dynamic balance of sediment was disturbed.
In Sickness and in Health—What Does the Oral Microbiome Mean to Us? An Ecological Perspective
Authors: Marsh P.D.
Published: January 2018

The oral microbiome is natural and has a symbiotic relationship with the host by delivering important benefits. In oral health, a dynamic balance is reached between the host, the environment, and the microbiome. However, the frequent intake of sugar and/or reductions in saliva flow results in extended periods of low pH in the biofilm, which disrupts this symbiotic relationship. Such conditions inhibit the growth of beneficial species and drive the selection of bacteria with an acid-producing/acid-tolerating phenotype, thereby increasing the risk of caries (dysbiosis). A more detailed understanding of the interdependencies and interactions that exist among the resident microbiota in dental biofilms, and an increased awareness of the relationship between the host and the oral microbiome, is providing new insights and fresh opportunities to promote symbiosis and prevent dysbiosis. These include modifying the oral microbiome (e.g., with prebiotics and probiotics), manipulating the oral environment to selectively favor the growth of beneficial species, and moderating the growth and metabolism of the biofilm to reduce the likelihood of dysbiosis. Evidence is provided to suggest that the regular provision of interventions that deliver small but relevant benefits, consistently over a prolonged period, can support the maintenance of a symbiotic oral microbiome.
Rebalancing the Caries Microbiome Dysbiosis: Targeted Treatment and Sugar Alcohols
Authors: Zhan L.
Published: January 2018

Dental caries is a disease that results from microbiome dysbiosis with the involvement of multiple cariogenic species, including mutans streptococci (MS), lactobacilli, Scardovia wiggsiae, and several Actinomyces species that have the cariogenic traits of acid production and acid tolerance. Sugar consumption also plays an important role interacting with microbiome dysbiosis, determining the fate of caries development. In addition, the MS transmission that encompasses multiple sources can have long-term impacts on the oral microbiome and caries development in children. Intervention in MS transmission in early childhood may promote effective long-term caries prevention. Anticaries regimens aimed against the above mechanisms will be important for successful caries management. Xylitol and erythritol may serve as good components of anticaries regimens as oral microbiome modifiers, sugar substitutes, and agents to prevent MS transmission in early childhood with both oral and systemic benefits. Further studies are needed to elucidate the mechanism of the anticaries effects of xylitol and erythritol with consideration of their impacts on the microbiome and bacterial virulence, in addition to cariogenic bacteria levels as well as their benefits for overall health. On the other hand, the anticaries agent C16G2, specifically targeting Streptococcus mutans, the most common cariogenic bacterial species, has shown good safety for short-term oral topical use and promising effects in reducing S. mutans in vitro and in vivo with the promotion of oral commensal bacteria. Future study on its anticaries effect will need to include its long-term impact on the oral microbiome and effects on other important cariogenic bacteria.
Dentist-Perceived Barriers and Attractors to Cognitive-Behavioral Treatment Provided by Mental Health Providers in Dental Practices
Authors: Heyman R.E. , Wojda A.K. , Eddy J.M. , Haydt N.C. , Geiger J.F. , Slep A.M. Smith
Published: January 2018

Over 1 in 5 dental patients report moderate to severe dental fear. Although the efficacy of cognitive-behavioral treatment (CBT) for dental fear has been examined in over 20 randomized controlled trials—with 2 meta-analyses finding strong average effect sizes ( d > 1)—CBT has received almost no dissemination beyond the specialty clinics that tested it. The challenge, then, is not how to treat dental fear but how to disseminate and implement such an evidence-based treatment in a way that recognizes the rewards and barriers in the US health care system. This mixed-method study investigated the potential of disseminating CBT through care from a mental health provider from within the dental home, a practice known as evidence-based collaborative care (EBCC). Two preadoption studies were conducted with practicing dentists drawn from a self-organized Practice-Based Research Network in the New York City metropolitan area. The first comprised 3 focus groups ( N = 17), and the second involved the administration of a survey ( N = 46). Focus group participants agreed that CBT for dental fear is worthy of consideration but identified several concerns regarding its appeal, feasibility, and application in community dental practices. Survey participants indicated endorsement of factors promoting the use of EBCC as a mechanism for CBT dissemination, with no factors receiving less than 50% support. Taken together, these findings indicate that EBCC may be a useful framework through which an evidence-based treatment for dental fear treatment can be delivered.
Moving from survival to fulfillment
Authors: Shaia Wendy E. , Finigan-Carr Nadine
Published: January 2018

Community schooling is an effective tool for combating the effects of poverty by integrating academic, social service, health, and economic supports for students, families, and community members. But this is complex work, requiring extraordinarily careful planning and assessment. This article suggests a planning framework that can help community schools succeed in coordinating wide-ranging program activities designed to support basic survival needs, help clients build power and self-determination, and support them in developing healthy relationships and hope for the future.
A powerful convergence
Authors: Jacobson David
Published: January 2018

Communities around the country are converging on a new approach to raising achievement for low-income children. This approach draws on two reform movements: (1) full-service community schools that provide wraparound health and social services to children and families, and (2) Prenatal through Grade 3 initiatives to improve quality, alignment, and coordination across early childhood and early elementary education. Examples in Cincinnati, Omaha, and Multnomah County demonstrate how communities can develop effective, results-oriented partnerships among elementary schools, community-based preschools, and other early childhood organizations.
Districts embrace the community to benefit all students
Authors: Weinzapfel Patricia
Published: January 2018

Moving from a traditional school district to one that embraces a community schools model requires fundamental shifts in organizational structure and practices. Evansville Vanderburgh School Corporation in southern Indiana and Vancouver Public Schools in Vancouver, Wash., are two districts that have navigated this change. Leaders from those districts describe their efforts to learn from data, build community support and staff buy in, leverage assets, build infrastructure, develop policies and procedures, and plan for sustaining their initiative.
The power of hmm…
Authors: Glazer Jeremy
Published: January 2018

Structured academic discussions can focus too much on academic language to the detriment of actual discussion, disempowering students with the very tools intended to enhance student voice. The author suggests a new goal for such classroom talk: encouraging students to generate ideas and questions that engage their peers by focusing on the unexpected, provoking them to reconsider their assumptions about the world.
Never too early to learn
Authors: Hooven Jennifer , Runkle Katherine , Strouse Laurie , Woods Misty , Frankenberg Erica
Published: January 2018

Four early childhood educators, along with a university researcher, describe their efforts to implement an antiracist, antibias curriculum in a daycare and preschool setting. Even very young children can learn important lessons about race, diversity, and equity, they argue, and teachers should not shy away from addressing these issues at staff meetings and in the classroom.
Leadership
Authors: Starr Joshua P.
Published: January 2018

Changing how we select school board members and how we approve district budgets could address long-standing challenges of local school governance.
Under the Law
Authors: Underwood Julie
Published: January 2018

The right to an education is guaranteed by international law in the Universal Declaration of Human Rights. Similarly, UNESCO’s Constitution sets out the right to an education as necessary to “prepare the children of the world for the responsibilities of freedom.” No such right is mentioned in the U.S. Constitution, though. Perhaps Congress or the Supreme Court would be sympathetic, however, to an argument for educational rights based on the 14th Amendment’s guarantee of the rights of citizenship.
Evaluating transportation infrastructure investment on a regional level: a system dynamics simulation
Authors: Wang Zhong , Zhang Yingying , Lian Lian , Chu Chenglong
Published: January 2018

Transportation infrastructure investment (TII) has significant influence on regional economic development. This paper aims to measure the potential economic impact of TII and to help policymakers to evaluate different alternatives and strategies at the regional level through a system dynamics (SD) approach. First, an SD model is established to simulate the impact of TII on the economy and employment. The relationship between transportation investments and economic development is examined and the relevant employment and economic indicators are identified. Second, the variables, flow diagrams, and structural equations of the SD model are defined. Third, the program Vensim is employed to establish the SD model with economy, transportation, and employment subsystems. It is then calibrated based on the historical statistics data in Liaoning Province, China. Finally, scenario analysis of different transportation investment plans is presented. The results will help investors, policymakers, and government agencies to estimate the potential outcomes of proposed transportation investment plans and to further develop optimal policies for transportation investment.
Leisure-Time Physical Activity, Subjective Age, and Self-Rated Memory in Middle-Aged and Older Adults
Authors: Chen Yen T. , Holahan Carole K. , Holahan Charles J. , Li Xiaoyin
Published: January 2018

Memory concerns are common in middle-aged and older adults. This study investigated the relation of leisure-time physical activity to self-rated memory and the possible mediating role of subjective age in this relationship in middle-aged and older adults. Cross-sectional analyses were conducted with a sample of 1,608 middle-aged and older adults from the second wave of the National Survey of Midlife Development in the United States (MIDUS2). In a path analysis conducted with Mplus, a higher level of leisure-time physical activity was associated with a more positive appraisal of memory compared to others of one’s age; younger subjective age partially mediated this relationship. Neither gender nor age-group moderated the association. Age, race, education, marital status, health status, and negative affect were controlled for in the analyses. These findings suggest a possible role of physical activity in countering the effects of age stereotypes on perceived memory.
Co-milled silica and coppiced wood biochars improve elongation and toughness in styrene-butadiene elastomeric composites while replacing carbon black
Authors: Peterson Steven C , Joshee Nirmal
Published: January 2018

Carbon black (CB) is a petroleum by-product with a million ton market in the US tire industry. Finding renewable substitutes for CB reduces dependence on oil and alleviates global warming. Biochar is a renewable source of carbon that has been studied previously as a replacement for CB in styrene-butadiene rubber (SBR) composites. However, biochar typically has lower carbon content, higher ash content, and larger particle size, which are all significant detractors to making biochar a viable drop-replacement for CB. In this study, high carbon and low ash biochars made from fast-growing Paulownia elongata and Populus tremuloides were co-milled with small amounts of silica in order to reduce the particle size, and the biochar/silica blends were then used to partially replace CB in SBR composites. Using this method both Paulownia and poplar biochars were able to replace 30% of the CB filler and improve elongation and toughness with virtually no loss of tensile strength, compared to the 100% CB-filled control composite.
Committed critical theory
Authors: Forst Rainer
Published: January 2018

In this article, I comment on Stephen White’s version of critical theory as presented in A Democratic Bearing. I specifically focus on his version of the “colonization thesis” and the social analysis this leads to. I also scrutinize his normative framework, especially the claim of non-foundationalism and the difference between his view and Kantian discourse theory.
Cigarette smoking and cerebral blood flow in a cohort of middle-aged adults
Authors: Elbejjani Martine , Auer Reto , Dolui Sudipto , Jacobs David R , Haight Thaddeus , Goff David C , Detre John A , Davatzikos Christos , Bryan R Nick , Launer Lenore J
Published: January 2018

Cigarette smoking is often associated with dementia. This association is thought to be mediated by hypoperfusion; however, how smoking behavior relates to cerebral blood flow (CBF) remains unclear. Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort (mean age = 50; n = 522), we examined the association between smoking behavior (status, cumulative pack-years, age at smoking initiation, and years since cessation) and CBF (arterial spin labeling) in brain lobes and regions linked to dementia. We used adjusted linear regression models and tested whether associations differed between current and former-smokers. Compared to never-smokers, former-smokers had lower CBF in the parietal and occipital lobes, cuneus, precuneus, putamen, and insula; in contrast, current-smokers did not have lower CBF. The relationship between pack-years and CBF was different between current and former-smokers ( p for interaction < 0.05): Among current-smokers, higher pack-years were associated with higher occipital, temporal, cuneus, putamen, insula, hippocampus, and caudate CBF; former-smokers had lower caudate CBF with increasing pack-years. Results show links between smoking and CBF at middle-age in regions implicated in cognitive and compulsive/addictive processes. Differences between current and former smoking suggest that distinct pathological and/or compensatory mechanisms may be involved depending on the timing and history of smoking exposure.
Topiramate-Induced Chest Pain: A Case Report
Authors: Ostroff Jared L. , LeClair (Barnet) Jessica N. , Ostroff Marissa L. , Laskey Corey S.
Published: January 2018

Background:

Topiramate, an anticonvulsant used for prophylaxis of migraines and epilepsy, is commonly associated with adverse effects of cognitive dulling and fatigue. Chest pain is a potential adverse effect that to our knowledge has not been reported with the use of topiramate.

Case Presentation:

We present the case of a 38-year-old female with a seizure disorder who experienced chest pain after the first dose of topiramate. On day 1, she presented to the emergency department, was admitted, and over the course of 3 days had a chest X-ray, electrocardiogram (ECG), and echocardiogram, and her vitals, basic metabolic panel, complete blood counts, troponin, and d-dimer levels were monitored. The chest pain improved when the topiramate was held. No identifiable causes of chest pain were apparent, other than the topiramate.

Discussion:

The Naranjo probability scale was utilized to determine the causality of topiramate. The resulting score of 3 indicates that it is possible that the chest pain was due to the topiramate.

Conclusion:

This report demonstrates an example of a patient who experienced chest pain possibly caused by the initiation of topiramate. The objective of this case report is to increase the awareness of chest pain as an adverse effect of topiramate.
Carbon-fibre-reinforced modified cyanate ester winding composites and their thermomechanical properties
Authors: Cui Yu Qing , Yin Zhong Wei
Published: January 2018

Although the extensive research has expanded on the modification of cyanate ester (CE) resins and the mechanical properties of CE composites, very few studies have been conducted on carbon fibre (CF)/modified CE winding composites and the thermomechanical properties of the composites. In this research, epoxy (EP)-modified novolac cyanate ester (NCE) and bismaleimide (BMI)-modified NCE resins were prepared. The CF/modified CE winding composites were manufactured, and their thermomechanical properties were tested. The optimal winding process was determined, and a preheating technique was implemented. Then, the EP/CE resin (10:90) and the BMI–DBA/CE resin (10:90) were selected as the resin matrix of the winding composite based on the viscosity properties, mechanical properties and thermal analysis (using thermogravimetric analysis and differential scanning calorimetry) of the modified CE resin. The selected resin exhibited good manufacturability at 70°C, good thermal stability and high Tg (above 370°C). The thermomechanical property tests indicate that the modified CE resin composite exhibits an outstanding mechanical strength at room temperature and at high temperatures (130°C, 150°C and 180°C) compared with that of the pure CE resin composite. The reasons for this enhancement can be attributed to a toughening mechanism and the effect of sizing agents on the CFs.
Primary Liver Cancers, Part 2
Authors: Jiang Kun , Centeno Barbara A.
Published: January 2018

Hepatocellular carcinoma (HCC) and primary intrahepatic cholangiocarcinoma (ICC) have been increasing in incidence worldwide and are leading causes of cancer death. Studies of the molecular alterations leading to these carcinomas provide insights into the key mechanisms involved. A literature review was conducted to identify articles with information relevant to current understanding of the etiologies and molecular pathogenesis of HCC and ICC. Chronic inflammatory diseases are the key etiological risk factors for both HCC and ICC, although other diseases play a role, and for many ICCs, an underlying risk factor is not identified. Mutations in catenin beta 1 ( CTNBB1) and tumor protein 53 (P53) are the main genetic alterations in HCC. Isocitrate dehydrogenases 1 and 2 (IDH1/2), KRAS protooncogene GTPase (KRAS), a RAS Viral Oncogene Homolog in neoroblastoma (NRAS) and P53 are primary genetic alterations in ICC. In both diseases, the mutational landscape is dependent on the underlying etiology. The most significant etiologies and genetic processes involved in the carcinogenesis of HCC and ICC are reviewed.
A Trauma-Informed Analysis of the Violence Against Women Act’s Provisions for Undocumented Immigrant Women
Authors: Murshid Nadine Shaanta , Bowen Elizabeth A.
Published: January 2018

Immigrant women in the United States are among the groups disproportionately affected by intimate partner violence (IPV). Undocumented immigrants generally have fewer resources for coping with violence and may experience a range of personal, cultural, and immigration status–related barriers to reporting violence and accessing help. Thus, undocumented immigrant victims of IPV could benefit significantly from policies that promote access to trauma-informed services and legal options. This article applies a trauma-informed policy analysis framework to the Violence Against Women Act’s immigration protections to demonstrate how the Act’s U-Visa provisions and implementation practices could be improved by incorporating trauma-informed principles of trustworthiness and transparency, empowerment, choice, safety, collaboration, and intersectionality.