bluuebunny/crossref_metadata_2025 huggingface dataset:
Person–Environment Fit: A Review of Its Basic Tenets
Authors: van Vianen Annelies E.M.
Published: January 2018

This review addresses the three basic principles of person–environment fit theory: (a) The person and the environment together predict human behavior better than each of them does separately; (b) outcomes are most optimal when personal attributes (e.g., needs, values) and environmental attributes (e.g., supplies, values) are compatible, irrespective of whether these attributes are rated as low, medium, or high; and (c) the direction of misfit between the person and the environment does not matter. My review of person–job and person–organization fit research that used polynomial regression to establish fit effects provides mixed support for the explanatory power of fit. Individuals report most optimal outcomes when there is fit on attributes they rate as highest, and they report lowest outcomes when the environment offers less than they need or desire. Linking these findings to individuals' abilities and opportunities to adapt, I reconsider fit theory and outline options for future research and practice.
Small-Molecule Activators of Protein Phosphatase 2A for the Treatment of Castration-Resistant Prostate Cancer
Authors: McClinch Kimberly , Avelar Rita A. , Callejas David , Izadmehr Sudeh , Wiredja Danica , Perl Abbey , Sangodkar Jaya , Kastrinsky David B. , Schlatzer Daniela , Cooper Maxwell , Kiselar Janna , Stachnik Agnes , Yao Shen , Hoon Divya , McQuaid Daniel , Zaware Nilesh , Gong Yixuan , Brautigan David L. , Plymate Stephen R. , Sprenger Cynthia C.T. , Oh William K. , Levine Alice C. , Kirschenbaum Alexander , Sfakianos John P. , Sears Rosalie , DiFeo Analisa , Ioannou Yiannis , Ohlmeyer Michael , Narla Goutham , Galsky Matthew D.
Published: January 2018

Primary prostate cancer is generally treatable by androgen deprivation therapy, however, later recurrences of castrate-resistant prostate cancer (CRPC) that are more difficult to treat nearly always occur due to aberrant reactivation of the androgen receptor (AR). In this study, we report that CRPC cells are particularly sensitive to the growth-inhibitory effects of reengineered tricyclic sulfonamides, a class of molecules that activate the protein phosphatase PP2A, which inhibits multiple oncogenic signaling pathways. Treatment of CRPC cells with small-molecule activators of PP2A (SMAP) in vitro decreased cellular viability and clonogenicity and induced apoptosis. SMAP treatment also induced an array of significant changes in the phosphoproteome, including most notably dephosphorylation of full-length and truncated isoforms of the AR and downregulation of its regulatory kinases in a dose-dependent and time-dependent manner. In murine xenograft models of human CRPC, the potent compound SMAP-2 exhibited efficacy comparable with enzalutamide in inhibiting tumor formation. Overall, our results provide a preclinical proof of concept for the efficacy of SMAP in AR degradation and CRPC treatment.

Significance: A novel class of small-molecule activators of the tumor suppressor PP2A, a serine/threonine phosphatase that inhibits many oncogenic signaling pathways, is shown to deregulate the phosphoproteome and to destabilize the androgen receptor in advanced prostate cancer. Cancer Res; 78(8); 2065–80. ©2018 AACR.
Selective mTORC2 Inhibitor Therapeutically Blocks Breast Cancer Cell Growth and Survival
Authors: Werfel Thomas A. , Wang Shan , Jackson Meredith A. , Kavanaugh Taylor E. , Joly Meghan Morrison , Lee Linus H. , Hicks Donna J. , Sanchez Violeta , Ericsson Paula Gonzalez , Kilchrist Kameron V. , Dimobi Somtochukwu C. , Sarett Samantha M. , Brantley-Sieders Dana M. , Cook Rebecca S. , Duvall Craig L.
Published: January 2018

Small-molecule inhibitors of the mTORC2 kinase (torkinibs) have shown efficacy in early clinical trials. However, the torkinibs under study also inhibit the other mTOR-containing complex mTORC1. While mTORC1/mTORC2 combined inhibition may be beneficial in cancer cells, recent reports describe compensatory cell survival upon mTORC1 inhibition due to loss of negative feedback on PI3K, increased autophagy, and increased macropinocytosis. Genetic models suggest that selective mTORC2 inhibition would be effective in breast cancers, but the lack of selective small-molecule inhibitors of mTORC2 have precluded testing of this hypothesis to date. Here we report the engineering of a nanoparticle-based RNAi therapeutic that can effectively silence the mTORC2 obligate cofactor Rictor. Nanoparticle-based Rictor ablation in HER2-amplified breast tumors was achieved following intratumoral and intravenous delivery, decreasing Akt phosphorylation and increasing tumor cell killing. Selective mTORC2 inhibition in vivo, combined with the HER2 inhibitor lapatinib, decreased the growth of HER2-amplified breast cancers to a greater extent than either agent alone, suggesting that mTORC2 promotes lapatinib resistance, but is overcome by mTORC2 inhibition. Importantly, selective mTORC2 inhibition was effective in a triple-negative breast cancer (TNBC) model, decreasing Akt phosphorylation and tumor growth, consistent with our findings that RICTOR mRNA correlates with worse outcome in patients with basal-like TNBC. Together, our results offer preclinical validation of a novel RNAi delivery platform for therapeutic gene ablation in breast cancer, and they show that mTORC2-selective targeting is feasible and efficacious in this disease setting.

Significance: This study describes a nanomedicine to effectively inhibit the growth regulatory kinase mTORC2 in a preclinical model of breast cancer, targeting an important pathogenic enzyme in that setting that has been undruggable to date. Cancer Res; 78(7); 1845–58. ©2018 AACR.
Carcinogen Exposure among Canadian Tobacco Users: Changes in NNK Exposure from 2007–2009 through 2012–2013
Authors: Czoli Christine D. , Hammond David
Published: January 2018

Background: Tobacco-specific nitrosamines (TSNAs) are a class of carcinogens found in tobacco products, whose levels can vary considerably depending on tobacco blends and manufacturing processes. The current study examined whether recent increases in levels of the TSNA NNK [4-(methylnitrosamino-1-(3-pyridyl)-1-butanone] in Canadian cigarettes translated into differences in exposure among Canadian tobacco users.

Methods: Nationally representative data from the Canadian Health Measures Survey (CHMS) were used to measure levels of total urinary NNAL [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol], a metabolite of the TSNA NNK, among tobacco users. Data from CHMS Cycle 3 (2012–13) were used to examine NNAL, and linear regression was used to examine predictors. Data from CHMS Cycle 1 (2007–09) and Cycle 3 (2012–13) were used to examine changes in NNAL over time.

Results: From 2007–2009 through 2012–2013, levels of creatinine-corrected NNAL increased by 64% (P < 0.0001). Levels of NNAL in 2012–2013 were higher among older respondents (P = 0.04), among females (P = 0.03), among respondents identifying as “white” and “Aboriginal” (P < 0.0001), and among those with greater daily cigarette consumption (P < 0.001), as well as greater levels of urinary free cotinine (P < 0.0001) and urinary creatinine (P < 0.0001).

Conclusions: The findings indicate that exposure to the TSNA NNK among Canadian tobacco users has increased considerably from 2007–2009 through 2012–2013, in parallel to changes in TSNA levels in Canadian cigarettes. In the absence of epidemiologic data, it is unclear whether this change translates into increased risk.

Impact: The study findings have potential implications for tobacco manufacturers, who bear a responsibility to reduce levels of tobacco carcinogens to the full extent possible. Cancer Epidemiol Biomarkers Prev; 27(3); 262–7. ©2018 AACR.
Further Investigation of the Role of ACYP2 and WFS1 Pharmacogenomic Variants in the Development of Cisplatin-Induced Ototoxicity in Testicular Cancer Patients
Authors: Drögemöller Britt I. , Brooks Beth , Critchley Carol , Monzon José G. , Wright Galen E.B. , Liu Geoffrey , Renouf Daniel J. , Kollmannsberger Christian K. , Bedard Philippe L. , Hayden Michael R. , Gelmon Karen A. , Carleton Bruce C. , Ross Colin J.D.
Published: January 2018

Purpose: Adverse drug reactions such as ototoxicity, which occurs in approximately one-fifth of adult patients who receive cisplatin treatment, can incur large socioeconomic burdens on patients with testicular cancer who develop this cancer during early adulthood. Recent genome-wide association studies have identified genetic variants in ACYP2 and WFS1 that are associated with cisplatin-induced ototoxicity. We sought to explore the role of these genetic susceptibility factors to cisplatin-induced ototoxicity in patients with testicular cancer.

Experimental Design: Extensive clinical and demographic data were collected for 229 patients with testicular cancer treated with cisplatin. Patients were genotyped for two variants, ACYP2 rs1872328 and WFS1 rs62283056, that have previously been associated with hearing loss in cisplatin-treated patients. Analyses were performed to investigate the association of these variants with ototoxicity in this cohort of adult patients with testicular cancer.

Results: Pharmacogenomic analyses revealed that ACYP2 rs1872328 was significantly associated with cisplatin-induced ototoxicity [P = 2.83 × 10−3, OR (95% CI):14.7 (2.6–84.2)]. WFS1 rs62283056 was not significantly associated with ototoxicity caused by cisplatin (P = 0.39); however, this variant was associated with hearing loss attributable to any cause [P = 5.67 × 10−3, OR (95% CI): 3.2 (1.4–7.7)].

Conclusions: This study has provided the first evidence for the role of ACYP2 rs1872328 in cisplatin-induced ototoxicity in patients with testicular cancer. These results support the use of this information to guide the development of strategies to prevent cisplatin-induced ototoxicity across cancers. Further, this study has highlighted the importance of phenotypic differences in replication studies and has provided further evidence for the role of WFS1 rs62283056 in susceptibility to hearing loss, which may be worsened by cisplatin treatment. Clin Cancer Res; 24(8); 1866–71. ©2018 AACR.
Glycogen Phosphorylase: A Novel Biomarker in Doxorubicin-Induced Cardiac Injury
Authors: Zhu Yueming , Gius David
Published: January 2018

Extracellular vesicles containing glycogen phosphorylase, brain/heart (PYGB) have been demonstrated as a sensitive biomarker for normal cardiac injuries for patients after chemotherapy. Oxidative stress was suggested to be the mechanism behind the chemotherapy-induced tissue damage and augmented with mitochondrial antioxidant could be an effective means of early intervention. Clin Cancer Res; 24(7); 1516–7. ©2018 AACR.

See related article by Yarana et al., p. 1644
Circulating MiR-146a May be a Potential Biomarker of Coronary Heart Disease in Patients with Subclinical Hypothyroidism
Authors: Quan Xiaohui , Ji Yuqiang , Zhang Chunyan , Guo Xuan , Zhang Yan , Jia Shan , Ma Weidong , Fan Yajie , Wang Congxia
Published: January 2018

Background/Aims: Subclinical hypothyroidism (SCH) plays a crucial role in the development and progression of coronary heart disease (CHD). However, any associated changes in the circulating microRNAs (miRNAs) levels and slightly elevated thyroid stimulating hormone (TSH) levels in CHD patients are unknown. miR-146a is a well known miRNA associated with inflammatory autoimmune diseases. Here, we evaluated miR-146a expression in patients, with the goal of re-evaluating the effect of SCH on CHD. Methods: A total of 192 study subjects who underwent coronary angiography for either suspected or confirmed CHD were enrolled in 3 groups: CHD with SCH, CHD alone, and healthy controls. The circulating levels of miR-146a were quantified using qRT-PCR. Results: Levels of miR-146a were positively correlated with CHD severity, as indicated by the Gensini score (r=0.354). The relative expression of miR-146a in the CHD+SCH, CHD and healthy control groups was 2.223±0.827, 1.588±0.726 and 0.632±0.309, respectively. Plasma TSH levels were positively correlated with miR-146a levels (r=0.321). According to multivariate logistic regression analyses, miR-146a levels were associated with the incidence of CHD in patients with SCH. For diagnosing CHD, the area under the ROC curve (AUC) of miR-146a and TSH was 0.779 and 0.752, respectively. When the TSH and miR-146a levels were combined to form a composite panel, the AUC of the panel was 0.858. Conclusion: Plasma miR-146a levels correlated with the severity of coronary atherosclerosis and increased with TSH slightly elevated in patients with CHD. Thus, miR-146a may have good predictive value for CHD among individuals with elevated TSH levels.
STIM2 (Stromal Interaction Molecule 2)–Mediated Increase in Resting Cytosolic Free Ca
2+
Concentration Stimulates PASMC Proliferation in Pulmonary Arterial Hypertension
Authors: Song Shanshan , Carr Shane G. , McDermott Kimberly M. , Rodriguez Marisela , Babicheva Aleksandra , Balistrieri Angela , Ayon Ramon J. , Wang Jian , Makino Ayako , Yuan Jason X.-J.
Published: January 2018

An increase in cytosolic free Ca
2+
concentration ([Ca
2+
]
cyt
) in pulmonary artery smooth muscle cells (PASMCs) triggers pulmonary vasoconstriction and stimulates PASMC proliferation leading to vascular wall thickening. Here, we report that STIM2 (stromal interaction molecule 2), a Ca
2+
sensor in the sarcoplasmic reticulum membrane, is required for raising the resting [Ca
2+
]
cyt
in PASMCs from patients with pulmonary arterial hypertension (PAH) and activating signaling cascades that stimulate PASMC proliferation and inhibit PASMC apoptosis. Downregulation of STIM2 in PAH-PASMCs reduces the resting [Ca
2+
]
cyt
, whereas overexpression of STIM2 in normal PASMCs increases the resting [Ca
2+
]
cyt
. The increased resting [Ca
2+
]
cyt
in PAH-PASMCs is associated with enhanced phosphorylation (p) of CREB (cAMP response element–binding protein), STAT3 (signal transducer and activator of transcription 3), and AKT, increased NFAT (nuclear factor of activated T-cell) nuclear translocation, and elevated level of Ki67 (a marker of cell proliferation). Furthermore, the STIM2-associated increase in the resting [Ca
2+
]
cyt
also upregulates the antiapoptotic protein Bcl-2 in PAH-PASMCs. Downregulation of STIM2 in PAH-PASMCs with siRNA (1) decreases the level of pCREB, pSTAT3, and pAKT and inhibits NFAT nuclear translocation, thereby attenuating proliferation, and (2) decreases Bcl-2, which leads to an increase of apoptosis. In summary, these data indicate that upregulated STIM2 in PAH-PASMCs, by raising the resting [Ca
2+
]
cyt
, contributes to enhancing PASMC proliferation by activating the CREB, STAT3, AKT, and NFAT signaling pathways and stimulating PASMC proliferation. The STIM2-associated increase in the resting [Ca
2+
]
cyt
is also involved in upregulating Bcl-2 that makes PAH-PASMCs resistant to apoptosis, and thus plays an important role in sustained pulmonary vasoconstriction and excessive pulmonary vascular remodeling in patients with PAH.
Determinants of Cardiometabolic Risk Factors in the First Decade of Life
Authors: Lurbe Empar , Aguilar Francisco , Álvarez Julio , Redon Pau , Torró Maria Isabel , Redon Josep
Published: January 2018

The present prospective study assessed the association of birth weight (BW) and growth pattern on cardiometabolic risk factors in a cohort followed from birth to 10 years of age. One hundred and forty-five subjects (73 girls) who fulfilled the inclusion criteria and had all their data recorded at birth and at 5 years were enrolled. Of these, 100 (52 girls) also recorded data at 10 years. Anthropometric measurements, office and 24-hour blood pressure, and metabolic parameters were obtained. At 5 years, both BW and current weight were determinants of blood pressure and metabolic parameters; however, as the subjects got older, the impact of body size increased. Higher BW and maternal obesity increased the risk of becoming obese at 5 years while this was reduced if breastfeeding. Maternal obesity was the only factor associated with becoming obese at 10 years. Twenty-two children at 10 years had insulin values ≥15 U/L, some of whom were persistent from 5 years while in others it increased afterward. Subjects with insulin values ≥15 U/L showed significant higher values of office systolic blood pressure, triglycerides, and uric acid and lower values of high-density lipoprotein than did those with normal insulin values. Highest weight gain from 5 to 10 years and lowest BW were the main determinants of high insulin levels. In conclusion, although BW was a proxy of the events during fetal life and projected its influence later, the influence of gaining weight was a key determinant in the risk to develop obesity and metabolic abnormalities.
Boethius and No End in Sight
Authors: Classen Albrecht
Published: January 2018

Previous scholarship has not considered the continued interest in the philosophical teachings by Boethius (d. 525) by early modern thinkers and poets. This article traces the continued flood of translations and editions of Boethius’s De consolatione philosophiae in Germany far into the seventeenth century and then unearths links between his philosophy and the sonnets by Andreas Gryphius and the epigrams by Johann Scheffler (Angelus Silesius). At first sight, we might not even recognize Boethian ideas in their poems, but the close analysis of images and concepts formulated in these German Baroque texts demonstrate strong similarities. Considering that Boethius was one of the important school authors even in the seventeenth century, it does not surprise us to discover direct echoes of his ideas in these literary reflections.
Pygmy grasshoppers (Orthoptera: Tetrigidae) of Vietnam: the genus Bolivaritettix Günther, 1939
Authors: STOROZHENKO SERGEY YU.
Published: January 2018

Vietnamese species of the genus Bolivaritettix Günther, 1939 are reviewed and illustrated. Altogether ten species are reported from Vietnam, of which five are new to science, namely—B. abruptus sp. nov., B. anaglypticus sp. nov., B. constrictus sp. nov., B. similis sp. nov., and B. vietnamensis sp. nov., while three species, B. sculptus (Bolívar, 1887), B. humeralis Günther, 1939 and B. celaenotus Zheng, Zhang et Dang, 2009, are recorded from Vietnam for the first time. A key to Vietnamese species is provided.
The Anticaries Efficacy of a 1.5% Arginine and Fluoride Toothpaste
Authors: Wolff M.S. , Schenkel A.B.
Published: January 2018

Dental caries remains a world-wide disease despite the global distribution of fluoride. It has become apparent that the introduction of significant levels of sugar (fermentable carbohydrate) into the diet has resulted in a change in the biofilm, encouraging acid formation. Further, there has been a shift in the microbiota in the biofilm to a flora that produces acid, and thrives and reproduces in an acidic environment. The management of caries activity under these conditions has focused on brushing to remove the biofilm with fluoride pastes, and high-dose fluoride treatments. Kleinberg, in the 1970s, identified an arginine-containing compound in saliva that several oral biofilm bacterial species metabolize to produce base. Multiple in situ and in vivo studies have been conducted, and have discussed the ability of multiple bacteria to increase the resting pH of the biofilm and even reduce the decrease in pH when the biofilm is challenged with glucose. This shift in resting pH can shift the level of caries formation by the biofilm. Here, we present 8 clinical studies, with different clinical designs, measuring different clinical outcomes, for a diverse, world-wide population. Each of these studies demonstrates reductions in caries formation beyond that seen with fluoride alone and several demonstrate the reversal of early caries lesions. Significant clinical research has been shown that 1.5% arginine combined with fluoride toothpaste has superior anti-caries efficacy to toothpaste containing fluoride alone.
Reminova and EAER: Keeping Enamel Whole through Caries Remineralization
Authors: Pitts N.B. , Wright J.P.
Published: January 2018

This article aims to outline the early development of a King’s College London dental spinout company, Reminova, formed to commercialize a novel clinical method of caries remineralization: electrically accelerated and enhanced remineralization (EAER). This method is being developed to address the unmet clinical need identified by modern caries management strategies to keep enamel “whole” through remineralization of clinical caries as a form of nonoperative caries treatment for initial-stage and moderate lesions. A progressive movement within dentistry is shifting away from the restorative-only model, which, it is suggested, has failed. The high prevalence of initial-stage caries across populations provides a significant opportunity to prevent restorations and reduce repeat restorations over a patient’s lifetime. Reminova has set out to provide a method to repair lesions without drilling, filling, pain, or injections. The article outlines the rationale for and the chronological stages of the technology and company development. It then outlines corroborative evidence to show that EAER treatment can, in this preliminary in vitro investigation, remineralize clinically significant caries throughout the depth of the lesion as measured by Knoop microhardness and corroborated by scanning electron microscopy. Furthermore, the presented data show that EAER-treated enamel is harder than the healthy enamel measured nearby in each sample and is very similar in appearance to healthy enamel from the subjective interpretation made possible by scanning electron microscopy imagery. The data presented also show that this more “complete” remineralization to a high hardness level has been achieved with 2 remineralizing agents via in vitro human tooth samples. The broad clinical potential of this new treatment methodology seems to be very encouraging from these results. Reminova will strive to continue its mission, to ensure that, in the future, dental teams will not need to drill holes for the treatment of initial-stage and moderate caries lesions.
The Editor’s Note
Authors: Richardson Joan
Published: January 2018

Kappan’s outgoing editor-in-chief describes challenges faced and accomplishments enjoyed over nearly a decade at the helm of the magazine.
Comal County, Texas
Authors: Walter Frank
Published: January 2018

Comal County, Texas, may be rural but its students face many of the same challenges as students in urban districts. Communities In Schools of South Central Texas works with the local school district to identify student needs and provide critical supports to help young people prepare for life after high school.
The devil is in the detail: What do citizens mean when they support stealth or participatory democracy?
Authors: Fernández-Martínez José Luis , Font Fábregas Joan
Published: January 2018

Recent research on citizen process preferences has highlighted three different models of decision making: representation, participation and stealth democracy. However, the meanings of the two alternatives to the prevailing representative model have not been fully explored. What do citizens have in mind when distinguishing between participatory and stealth models of democracy? Using survey data from several Western European countries, the article explores one distinction within preferences for each of the models: the preference for more referendum-based versus dynamic responsiveness-based solutions on the participatory side and for expert-based versus business-based solutions on the stealth side. The article ends by exploring the impact of left-right ideology and education upon these preferences. The explanatory power of the variables is greater for understanding the internal distinction of the stealth model than the participatory one.
Offender–victim relationship and offender motivation in the context of indirect cyber abuse
Authors: Vakhitova Zarina , Webster Julianne , Alston-Knox Clair , Reynald Danielle , Townsley Michael
Published: January 2018

Cyber abuse can be executed directly (e.g. by sending derogatory emails or text messages addressed to the victim) or indirectly (e.g. by posting derogatory, private or false information, documents, images or videos about the victim online). This exploratory, mixed-method triangulated study examines cyber abuse crime events with the goal of identifying factors associated with the increased risk of personal victimization from both direct and indirect methods of cyber abuse. First, in-depth qualitative interviews with cyber abuse victims ( n = 12) were conducted. The interviews were analysed using thematic analysis to generate hypotheses. These hypotheses were then tested using content analysis of newspaper reports ( n = 110) and victims’ posts on online forums ( n = 91) describing incidents of cyber abuse. Logistic regression using Bayesian Model Averaging analysis revealed that the combination of a prior offender–victim relationship and expressive motivation best predicts the use of indirect methods of cyber abuse, while direct methods of cyber abuse are more likely to occur when the offender does not know the victim and is motivated by instrumental ends. Implications for crime prevention are also discussed.
Opioids and Social Connection
Authors: Inagaki Tristen K.
Published: January 2018

Social connection, the pleasurable, subjective experience of feeling close to and bonded with other people, is critical for well-being and continued social bonding. Despite the importance of social connection for many important outcomes, few researchers have experimentally examined how humans connect with those to whom they feel close. The strongest insights into the biological bases of social connection come from animal research, which shows that social bonds rely on the same neurochemicals that support general motivation. One class of neurochemicals, opioids, has received increased attention in recent years with the rise of pharmacological methods to manipulate opioids in humans. This article reviews emerging findings to show that opioids affect social feelings, behaviors, and perceptions in both positive and negative social experiences and concludes with the implications of such findings. Future work should consider the subjective feelings of social connection felt during interactions with close social contacts in order to further the understanding of social connection.
Variations in Velopharyngeal Structure in Adults With Repaired Cleft Palate
Authors: Perry Jamie L. , Kotlarek Katelyn J. , Sutton Bradley P. , Kuehn David P. , Jaskolka Michael S. , Fang Xiangming , Point Stuart W , Rauccio Frank
Published: January 2018

Objective:

The purpose of this study was to examine differences in velopharyngeal structures between adults with repaired cleft palate and normal resonance and adults without cleft palate.

Design:

Thirty-six English-speaking adults, including 6 adults (2 males and 4 females) with repaired cleft palate (M = 32.5 years of age, SD = 17.4 years) and 30 adults (15 males and 15 females) without cleft palate (M = 23.3 years of age, SD = 4.1 years), participated in the study. Fourteen velopharyngeal measures were obtained on magnetic resonance images and compared between groups (cleft and noncleft).

Results:

After adjusting for body size and sex effects, there was a statistically significant difference between groups for 10 out of the 14 velopharyngeal measures. Compared to those without cleft palate, participants with repaired cleft palate had a significantly shorter hard palate height and length, shorter levator muscle length, shorter intravelar segment, more acute levator angles of origin, shorter and thinner velum, and greater pharyngeal depth.

Conclusion:

Although significant differences were evident in the cleft palate group, individuals displayed normal resonance. These findings suggest that a wide variability in velopharyngeal anatomy can occur in the presence of normal resonance, particularly for those with repaired cleft palate. Future research is needed to understand how anatomic variability impacts function, such as during speech.
“I Don’t Know That I’ve Ever Felt Like I Got the Full Story”: A Qualitative Study of Courtroom Interactions Between Judges and Litigants in Domestic Violence Protective Order Cases
Authors: Person Cara J. , Moracco Kathryn E. (Beth) , Agnew-Brune Christine , Bowling J. Michael
Published: January 2018

One in three U.S. women has experienced intimate partner violence (IPV) and many seek domestic violence protective orders (DVPOs) for secondary IPV prevention. Because judges have considerable autonomy making DVPO decisions, there is a need to describe how courtroom interactions and information available to judges may influence DVPO dispositions. We conducted DVPO hearing observations and phone interviews with District Court Judges. Qualitative themes emerged that may influence judges’ decision making in DVPO hearings: case information availability, judge engagement level, and litigant credibility. Recommendations include more time for judges to review case files, IPV-related training for judges, and increased court advocate use.
Biochemical, Oxidative, and Physiological Changes Caused by Acute Exposure of Fentanyl and Its 3 Analogs in Rodents
Authors: Yadav Shiv Kumar , Kumar Deo , Kumar Pravin , Gupta Pradeep Kumar , Bhattacharya Rahul
Published: January 2018

Synthesis and bioefficacy of fentanyl and its 8 new 1-substituted analogs (1-8) were earlier reported by us. Of these 8 compounds, N-(1-(2-phenoxyethyl)-4-piperidinyl)propionanilide (2), N-isopropyl-3-(4-( N-phenylpropionamido)piperidin-1-yl)propanamide (5), and N- t-butyl-3-(4-( N-phenylpropionamido)piperidin-1-yl) propanamide (6) were found to be more effective and less toxic compared to fentanyl. The present study reports the acute effect of fentanyl (0.50 Median Lethal Dose (LD50); intraperitoneal) and its 3 analogs (2, 5, and 6) on various biochemical and oxidative parameters in mice and various physiological parameters in rats. Blood alkaline phosphatase (1 hour and 7 days) and urea levels (1 hour) were significantly elevated by fentanyl, while alanine aminotransferase levels (1 hour) were increased by both fentanyl and analog 2 compared to the corresponding control. Increase in partial pressure of carbon dioxide and decrease in partial pressure of oxygen were also caused by fentanyl and analog 2 (1 hour). Analog 6 alone elevated malondialdehyde levels in the brain, liver, and kidney tissues (7 days). The LD50 of fentanyl and analogs 2, 5, and 6 were found to be 0.879, 87.88, 69.80, and 55.44 mg/kg, respectively, in rats. Significant decrease in heart rate, mean arterial pressure, respiratory rate (RR), and neuromuscular transmission was produced by fentanyl and analog 2, while analog 5 decreased the RR alone. The changes, particularly the respiratory depression, were found to be reversed by naloxone, a μ-receptor antagonist. Thereby, indicating involvement of μ-receptor mediated effects of the compounds. To conclude, all the analogs were found to be less toxic compared to fentanyl, suggesting their possible role in pain management.
Sydney as an Indigenous place: “Goanna walking” brings people together
Authors: Rey Jo , Harrison Neil
Published: January 2018

Sydney, Australia, is rarely seen as an Indigenous place, yet over 52,000 Indigenous people live here. “Indigeneity” persists in educational discourse as a remote phenomenon, but the research reveals otherwise for many Indigenous people who continue to live in Sydney. This is reflected in the contemporary lives of seven Dharug women who constitute the basis of a doctoral project. The seven women disclose how caring and connectivity to place and people continue to be important markers of belonging to Country in the city. This article also draws on Judith Butler’s work to investigate the conditions of possibility for sustained collaboration between Indigenous and non-Indigenous people in Sydney. Through a collaborative project between local Dharug artists and teacher education students, we find that cross-cultural understandings are built through vulnerabilities, as much as they are through reason. Shared vulnerability provides the conditions for meeting on Country, and “goanna walking” takes us there.
Type 1 long QT syndrome and psychological stress in a laboratory setting
Authors: Määttänen Ilmari , Ravaja Niklas , Henttonen Pentti , Puttonen Sampsa , Paavonen Kristian , Swan Heikki , Hintsa Taina
Published: January 2018

Trait-like sensitivity to stress in long QT syndrome patients has been documented previously. In addition, mental stress has been associated with symptomatic status of long QT syndrome. We examined whether the symptomatic type 1 long QT syndrome patients would be more sensitive to mental stress compared to asymptomatic patients and whether there would be differences in task-related physiological stress reactions between type 1 long QT syndrome patients and healthy individuals. The study population consisted of 21 symptomatic and 23 asymptomatic molecularly defined KCNQ1 mutation carriers, their 32 non-carrier relatives and 46 non-related healthy controls, with mean ages of 37, 39, 35 and 23 years, respectively. Electrocardiography was utilised to calculate inter-beat interval and high frequency and low frequency heart rate variability. Blood pressure was measured and mean arterial pressure and pulse pressure were calculated. Stress was induced using three different tasks: mental arithmetic, reaction time and public speech. Stress responses of symptomatic and asymptomatic type 1 long QT syndrome patients were not statistically different in any of the stress tasks. Short-term physiological stress reactivity of symptomatic type 1 long QT syndrome patients appears to be normal and does not enhance the risk assessment of asymptomatic mutation carriers.
Beyond Boundaries: The Development and Potential of Ethnography in the Study of Sport and Physical Culture
Authors: Gibson Kass , Atkinson Michael
Published: January 2018

Ethnographic approaches to the study of sport and physical culture have developed primarily within physical education and kinesiology programs and are typically framed in dialogue with sociological theorizing of agency, structure, power, and inequality. Beginning with reference to anthropology and sociology, we review the emergence, development, and subsequent transdisciplinary travels of ethnographic study of sport and physical culture. In doing so, we underscore the importance of theory, context, and disciplinary tradition in the development of sporting ethnographies. We then critically outline the place of ethnography in physical cultural studies (PCS). Rather than exhuming existing debates about the originality and uniqueness of the PCS enterprise, we highlight the need to decenter the hyper-reflexive researcher and advocate for the consideration of pleasure in ethnographic studies to achieve the interventionist goals PCS protagonists set themselves.
Volumetric abnormalities of the brain in a rat model of recurrent headache
Authors: Jia Zhihua , Tang Wenjing , Zhao Dengfa , Hu Guanqun , Li Ruisheng , Yu Shengyuan
Published: January 2018

Voxel-based morphometry is used to detect structural brain changes in patients with migraine. However, the relevance of migraine and structural changes is not clear. This study investigated structural brain abnormalities based on voxel-based morphometry using a rat model of recurrent headache. The rat model was established by infusing an inflammatory soup through supradural catheters in conscious male rats. Rats were subgrouped according to the frequency and duration of the inflammatory soup infusion. Tactile sensory testing was conducted prior to infusion of the inflammatory soup or saline. The periorbital tactile thresholds in the high-frequency inflammatory soup stimulation group declined persistently from day 5. Increased white matter volume was observed in the rats three weeks after inflammatory soup stimulation, brainstem in the in the low-frequency inflammatory soup-infusion group and cortex in the high-frequency inflammatory soup-infusion group. After six weeks’ stimulation, rats showed gray matter volume changes. The brain structural abnormalities recovered after the stimulation was stopped in the low-frequency inflammatory soup-infused rats and persisted even after the high-frequency inflammatory soup stimulus stopped. The changes of voxel-based morphometry in migraineurs may be the result of recurrent headache. Cognition, memory, and learning may play an important role in the chronification of migraines. Reducing migraine attacks has the promise of preventing chronicity of migraine.
Involvement of neutrophils and interleukin-18 in nociception in a mouse model of muscle pain
Authors: Yoshida Shinichirou , Hagiwara Yoshihiro , Tsuchiya Masahiro , Shinoda Masamichi , Koide Masashi , Hatakeyama Hiroyasu , Chaweewannakorn Chayanit , Yano Toshihisa , Sogi Yasuhito , Itaya Nobuyuki , Sekiguchi Takuya , Yabe Yutaka , Sasaki Keiichi , Kanzaki Makoto , Itoi Eiji
Published: January 2018

Muscle pain is a common condition that relates to various pathologies. Muscle overuse induces muscle pain, and neutrophils are key players in pain production. Neutrophils also play a central role in chronic pain by secreting interleukin (IL)-18. The aim of this study was to investigate the involvement of neutrophils and IL-18 in a mouse model of muscle pain. The right hind leg muscles of BALB/c mice were stimulated electrically to induce excessive muscle contraction. The left hind leg muscles were not stimulated. The pressure pain threshold, number of neutrophils, and IL-18 levels were investigated. Furthermore, the effects of the IL-18-binding protein and Brilliant Blue G on pain were investigated. In stimulated muscles, pressure pain thresholds decreased, and neutrophil and IL-18 levels increased compared with that in non-stimulated muscles. The administration of IL-18-binding protein and Brilliant Blue G attenuated hyperalgesia caused by excessive muscle contraction. These results suggest that increased IL-18 secretion from larger numbers of neutrophils elicits mechanical hyperalgesia.
Defining the relationship between COPD and CVD: what are the implications for clinical practice?
Authors: Morgan Ann D , Zakeri Rosita , Quint Jennifer K
Published: January 2018

Cardiovascular diseases (CVDs) are arguably the most important comorbidities in chronic obstructive pulmonary disease (COPD). CVDs are common in people with COPD, and their presence is associated with increased risk for hospitalization, longer length of stay and all-cause and CVD-related mortality. The economic burden associated with CVD in this population is considerable and the cumulative cost of treating comorbidities may even exceed that of treating COPD itself.

Our understanding of the biological mechanisms that link COPD and various forms of CVD has improved significantly over the past decade. But despite broad acceptance of the prognostic significance of CVDs in COPD, there remains widespread under-recognition and undertreatment of comorbid CVD in this population. The reasons for this are unclear; however institutional barriers and a lack of evidence-based guidelines for the management of CVD in people with COPD may be contributory factors.

In this review, we summarize current knowledge relating to the prevalence and incidence of CVD in people with COPD and the mechanisms that underlie their coexistence. We discuss the implications for clinical practice and highlight opportunities for improved prevention and treatment of CVD in people with COPD. While we advocate more active assessment for signs of cardiovascular conditions across all age groups and all stages of COPD severity, we suggest targeting those aged under 65 years. Evidence indicates that the increased risks for CVD are particularly pronounced in COPD patients in mid-to-late-middle-age and thus it is in this age group that the benefits of early intervention may prove to be the most effective.
The gap between behavioral risk status and willingness to change behavior among healthcare professionals
Authors: Kasila K , Hallman M , Kautiainen H , Vanhala M , Kettunen T
Published: January 2018

Aims:

This study explored behavioral health risk factors among healthcare professionals and investigated the at-risk persons’ satisfaction with their health habits and ongoing change attempts.

Methods:

The study was based on a cross-sectional web-based survey directed at the nurses and physicians ( N = 1233) in Finnish healthcare. Obesity, low physical activity, smoking, and risky alcohol drinking were used as behavioral health risk factors.

Results:

In all, 70% of the participants had at least one behavioral risk factor, and a significant number of at-risk persons were satisfied with their health habits and had no ongoing change process. Good self-rated health and good self-rated work ability were significantly associated with whether a participant had a behavioral health risk factor.

Conclusion:

Overall, unhealthy behaviors and a lack of ongoing change attempts were commonly observed among healthcare professionals. Work in healthcare is demanding, and healthy lifestyles can support coping. Thus, healthy lifestyle programs should also be targeted to healthcare professionals.
Diverse cutaneous adverse eruptions caused by anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) immunotherapies: clinical features and management
Authors: Shen John , Chang Jason , Mendenhall Melody , Cherry Grace , Goldman Jonathan W. , Kulkarni Rajan P.
Published: January 2018

Background:

The anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) immunotherapies have shown exceptional activity in many cancers. However, these immunotherapies can also result in diverse adverse cutaneous eruptions that need to be better characterized for ongoing management. The objective was to provide clinical and histopathologic descriptions of the variety of cutaneous adverse events seen in patients who received anti-PD-1/PD-L1 treatment and discuss their management.

Methods:

Patients with advanced cancers in clinical trials at University of California Los Angeles (UCLA), receiving anti-PD-1/PD-L1 treatment between 2012 and 2016 who developed cutaneous eruptions and were evaluated in the dermatology clinic were included in this retrospective case series study. A total of 16 patients were included in this study; of these, five were treated with pembrolizumab alone, two with avelumab alone, eight with nivolumab plus ipilimumab and one with nivolumab plus T-Vec. Of these 16 patients, eight had received systemic chemotherapy, six had received radiotherapy, and one had received trememlimumab prior to the immunotherapies described in this study.

Results:

Cutaneous eruptions occurred at variable times, from week 1 to 88, with a median of 11.5 weeks; the morphologies included lichenoid, bullous, psoriasiform, macular, morbiliform appearances, and alopecia which were confirmed histopathologically in several of the cases. All cutaneous immune-related adverse events were either grade 1 or 2. Ten patients were treated with topical corticosteroids, and one also received NBUVB. Four patients eventually required systemic steroids. Three required discontinuation of their anti-PD-1/PD-L1 therapy secondary to the cutaneous eruptions.

Conclusions:

There are several different types of adverse cutaneous morphologies that may be seen with administration of PD-1 and PD-L1 inhibitors. Identifying the patterns of eruption may assist in prompt treatment. Most eruptions could be managed with topical corticosteroids and without discontinuation of the systemic treatment.
Updating a Classic: A New Generation of Vignette Experiments Involving Iterative Decision Making
Authors: Freedman Gili , Seidman Max , Flanagan Mary , Green Melanie C. , Kaufman Geoff
Published: January 2018

Although the vignette method is widely used in psychology, it is often implemented without the key feature of iterative decision making that can affect the eventual outcome of the vignettes. This Tutorial provides an explanation of how to use Twine, an interactive narrative platform, to create vignettes with iterative decision making. Twine is an especially useful tool for experiments involving branching narratives, spatial navigation, and resource allocation. We provide code for creating exemplar experiments in social and cognitive psychology, as well as behavioral economics, and explain how to integrate Twine projects with survey-management platforms, such as Qualtrics. After following this Tutorial, researchers will be able to use Twine in their experiments to update the classic vignette method by incorporating iterative decision-making tasks.
Multi-drug resistant Acinetobacter species: a seven-year experience from a tertiary care center in Lebanon
Authors: Kanafani Zeina A. , Zahreddine Nada , Tayyar Ralph , Sfeir Jad , Araj George F. , Matar Ghassan M. , Kanj Souha S.
Published: January 2018

Background

Acinetobacter species have become increasingly common in the intensive care units (ICU) over the past two decades, causing serious infections. At the American University of Beirut Medical Center, the incidence of multi-drug resistant Acinetobacter baumannii (MDR-Ab) infections in the ICU increased sharply in 2007 by around 120%, and these infections have continued to cause a serious problem to this day.

Methods

We conducted a seven-year prospective cohort study between 2007 and 2014 in the ICU. Early in the epidemic, a case-control study was performed that included MDR-Ab cases diagnosed between 2007 and 2008 and uninfected controls admitted to the ICU during the same time.

Results

The total number of patients with MDR-Ab infections diagnosed between 2007 and 2014 was 128. There were also 99 patients with MDR-Ab colonization without evidence of active infection between 2011 and 2014. The incidence of MDR-Ab transmission was 315.4 cases/1000 ICU patient-days. The majority of infections were considered hospital-acquired (84%) and most consisted of respiratory infections (53.1%). The mortality rate of patients with MDR-Ab ranged from 52% to 66%.

Conclusion

MDR-Ab infections mostly consisted of ventilator-associated pneumonia and were associated with a very high mortality rate. Infection control measures should be reinforced to control the transmission of these organisms in the ICU.
A scheme to analyze agent-based social simulations using exploratory data mining techniques
Authors: Patel M. Hammad , Abbasi Mujtaba Ahmed , Saeed M. , Alam Shah Jamal
Published: January 2018

Exploring and understanding outputs from agent-based models is challenging due to a relatively higher number of parameters and multidimensionality of the generated data. We use a combination of exploratory and data mining techniques to understand data generated from an existing agent-based model to understand the model’s behavior and its sensitivity to initial configurations of its parameters. This is a step in the direction of an ongoing research in the social simulation community to incorporate more sophisticated techniques to better understand how different parameters and internal processes influence outcomes of agent-based models.