bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance of Current Thromboembolism Risk Assessment Tools in Patients With Gastric Cancer and Validity After First Treatment
Authors: Fuentes Harry E. , Paz L. H. , Wang Y. , Oramas D. M. , Simons C. R. , Tafur A. J.
Published: September 2017

Patients with gastric cancer (GC) are at higher risk of thromboembolism when compared to other solid tumors. We aim to determine the predictive performance of current venous thromboembolism (VTE) predictive tools and their variability and validity after first treatment. Single institution cohort of GC-treated patients (2010*15). We abstracted predictive tools, validated for VTE prediction in patient with cancer; including the Khorana Score (KRS), platelet to lymphocyte ratio (PLR), and neutrophil to lymphocyte ratio (NLR). The primary outcome was CAT prediction. We included 112 patients who were predominantly men (66%), 58 (51-64)-year-olds, with adenocarcinoma (84%) and advanced disease (59%). The median follow-up was 21.3 months (9.5-42.6). The VTE occurrence was 12%. The median time from diagnosis to VTE occurrence was 59 days (36-258). In our cohort, performance status (PS; hazard ratio [HR], 8.02; 95% confidence interval [CI], 2.37-27.14; P < .01) was an independent predictor of VTE whereas KRS (univariate HR, 2.3; 95% CI, 0.7-7.4; P = .17), PLR (univariate HR, 0.8; 95% CI, 0.2-3.1; P = .8), and NLR (univariate HR, 0.8; 95% CI, 0.3-2.5; P = .8) at baseline were not associated with VTE risk. The posttreatment KRS was an independent predictor of VTE (HR, 3.69; 95% CI, 1.17-11.65; P = .25) along with PS (HR, 7.58; 95% CI, 2.27-25.33; P = .01). Posttreatment KRS appears as a valid tool to identify patients with GC at high risk of VTE after first cancer treatment.
Analysis of Risk Factors of Stroke and Venous Thromboembolism in Females With Oral Contraceptives Use
Authors: Dulicek Petr , Ivanova Eva , Kostal Milan , Sadilek Petr , Beranek Martin , Zak Pavel , Hirmerova Jana
Published: September 2017

Thrombotic diathesis has been a well-known complication of oral contraceptive use for more than 50 years. This is true not only for venous thrombosis but also for an arterial one. The etiology is usually multifactorial and depends on several additional risk factors. We analyzed the prevalence of inherited and acquired thrombophilia in a cohort of 770 females who had a thrombotic event in association with oral contraceptive use (700 women with venous thromboembolism [VTE], 70 with stroke). Moreover, we tried to identify additional risk factors. Inherited thrombophilia was found in 44.5% with higher frequency in the cohort with VTE (42%) than in females with stroke (24%). The most frequent finding was factor V Leiden. Cigarette smoking was significantly more frequent in the group with stroke (50% vs 25%). The prevalence of cigarette smoking in the group with VTE did not exceed the frequency in general population. Women on oral contraceptive pills have higher risk of venous as well as arterial thrombosis. The risk of venous thrombosis is increased in females with inherited thrombophilia, whereas those with some additional acquired risk factors (especially smoking) may be predisposed to arterial thrombosis. However, the absolute risk of thrombosis in healthy women is low, far less than the risk of unintended pregnancy. Moreover, the risk may be reduced by keeping some rules before the prescription of the pills, healthy life style, and a proper choice of contraception.
“Wearing My Spiritual Jacket”: The Role of Spirituality as a Coping Mechanism Among African American Youth
Authors: Dill LeConté J.
Published: September 2017

There is growing evidence in the theoretical literature regarding the importance of religion and religiosity in people’s lives, particularly concerning their health and well-being. Spirituality, a related but different concept, has been less well studied, especially empirically, but shows promise as a mechanism for coping with deleterious social and health circumstances. This article details a qualitative exploration of the role of spiritual coping in the lives of urban African American youth. Data were gathered through in-depth, semistructured interviews with 20 African American youth, ages 12 to 20 years. The findings indicate that urban African American youth have multifaceted dimensions of their spirituality, including the role of prayer in their lives, an unwavering faith in a higher power, and the importance of giving back to their communities. Such findings offer counterstories, generated through ethnographic research, to the dominant discourses regarding urban African American youth. Ultimately, this study’s findings have implications for research and practice related to the mechanisms of both ill-health and wellness among youth.
Body appreciation, anxiety, and depression among a racially diverse sample of women
Authors: Ramseyer Winter Virginia , Gillen Meghan M , Cahill Laura , Jones Aubrey , Ward Michaella
Published: September 2017

This study aims to explore correlates between body appreciation and mental health among a racially and ethnically diverse sample of adult women using validated measures. The sample included racially and ethnically diverse women ( N = 497) from various socioeconomic levels. Linear regression results indicated that body appreciation was significantly and inversely associated with depression ( b = −3.68; p < 0.001). In this sample, as body appreciation increased, depression scores decreased. Similarly, body appreciation was significantly and inversely associated with anxiety among this sample ( b = −1.78; p < 0.001). This article concludes with a discussion of findings and implications.
Crafting place: Women’s everyday creativity in placemaking processes
Authors: Platt Louise C
Published: September 2017

Amid a resurgence of domestic craft, this article contends that everyday creative practices of women are part of placemaking processes in the creative city. Specifically, the research focuses on Liverpool in the Northwest of England, the so-called (and self-proclaimed) ‘centre of the creative universe’. This article utilized in-depth semi-structured interviews with members of knitting groups and the city centre Women’s Institute to explore how women use craft practice to create a sense of self and attachment to place. The idea of women gathering to craft is enduring, and is examined here to understand affective labour and the role that creativity plays in the urban experience of women. It is argued that the groups demonstrate a lack of engagement with the wider market and official placemaking processes, but instead demonstrate an element of self-valorization. The article challenges thinking around culture-led placemaking in cities like Liverpool, where discourses of creativity have been used as a driver for regeneration by shifting the emphasis onto seemingly banal settings on the edges of the so-called creative city. While urban placemakers have been more recently concerned with developing hubs of creative industries, the role of these groups that are not producing a profitable ‘product’ should not be underestimated or exploited.
Hidden heirlooms: Keeping family secrets across generations
Authors: Barnwell Ashley
Published: September 2017

This article explores how wider national narratives facilitate families’ choices about what information to keep secret over time. I argue that attention to the ways family secrets operate reveals how social and moral codes are both sustained and challenged on an intimate scale. The article also makes an argument for using life writing and literature to explore the often-illusive contours of family secrets. To illustrate, I examine Lynette Russell’s memoir A Little Bird Told Me: Family Secrets, Necessary Lies and Richard Flanagan’s novel Death of a River Guide. Anchoring the analysis within the transition from colonial to postcolonial societies, these texts lend insight into the collective practices families use to manage secrets and to construct socially sanctioned identities. The discussion foregrounds the enduring impact of colonial policies upon the intimate formation of families, and the role families play in reproducing and challenging these legacies via collective secret-keeping and silences.
Journalistic interventions: The structural factors affecting the global emergence of fact-checking
Authors: Amazeen Michelle A
Published: September 2017

Since the emergence of FactCheck.org in the United States in 2003, fact-checking interventions have expanded both domestically and globally. The Duke Reporter’s Lab identified nearly 100 active initiatives around the world in 2016. Building off of previous exploratory work by Amazeen, this research utilizes the framework of critical juncture theory to examine why fact-checking interventions are spreading globally at this point in time. Seen as a professional reform movement in the journalistic community, historical research on reform movements suggests several possible factors influencing the emergence of fact-checking such as a decline in journalism, easy access to technology for the masses, and socio-political strife. This study offers empirical support that fact-checking may be understood as a democracy-building tool that emerges where democratic institutions are perceived to be weak or are under threat and examines similarities between the growth of fact-checking interventions and previous consumer reform movements. As politics increasingly adopts strategies orchestrated by marketing and advertising consultants and agencies – exemplified in the Brexit referendum – political fact-checking may benefit from examining the path of consumer reform movements. For, before fact-checking can be effective at informing individuals, it must first establish itself within a structural environment.
Advancing rigour in solicited diary research
Authors: Filep Crystal Victoria , Turner Sarah , Eidse Noelani , Thompson-Fawcett Michelle , Fitzsimons Sean
Published: September 2017

Solicited diaries/journals are increasingly popular as an innovative qualitative method in the social sciences for better understanding people’s everyday lived experiences. In this article we create a framework for maintaining rigour while using such diaries. First, we systematically evaluate 43 research papers focusing on the method, drawing on Baxter and Eyles’ (1997) seminal evaluation of rigour in qualitative human geography research. We ascertain that significant improvements could be made to procedures for obtaining and analysing diary content. Second, we develop a framework to encourage rigour in diary research. We test our framework by evaluating research conducted by two of our authors who employed solicited diaries with street vendors in Vietnam. We propose that our analysis and framework can help social scientists improve the rigour of solicited diaries as a research method, and provide a model for enhancing rigour in other emerging qualitative approaches.
A decision-making tool for building clinical ethics capacity among Irish health professionals
Authors: Campbell Louise , McCarthy Joan
Published: September 2017

Although clinical ethics support services are becoming increasingly prevalent in Europe and North America, they remain an uncommon feature of the Irish healthcare system and Irish health professionals lack formal support when faced with ethically challenging cases. We have developed a variant on existing clinical ethics decision-making tools which is designed to build capacity and confidence amongst Irish practitioners and enable them to confront challenging situations in the absence of any dedicated support structure. The tool provided below follows a transparent stepwise procedure which avoids an overcomplicated analysis while remaining sensitive to the complexity of the issues addressed. The novelty of the tool lies in the explicit association it makes between each step in the process and one or more responsibilities based on established norms of ethical decision-making in the public domain.
A Story of Becoming: Entanglement, Settler Ghosts, and Postcolonial Counterstories
Authors: Fitzpatrick Esther
Published: September 2017

“Ūkaipo,” she tells me. “Your place of contentment.” And there it is—a gift. The gift of a word to story my “belonging” to my place. The gift from my friend, a Māori scholar. The gift of an indigenous Māori word to a Pākehā, the descendent of a colonial New Zealander. I receive this gift as a taonga, a treasure. As a critical autoethnography, this article demonstrates the process of layering the personal story alongside the wider historical and social story, and alongside stories of other peoples, through a Critical Family History. As a strategy of decolonization, the stories are interrogated using critical theory. Cognizant of Smith’s seminal work on decolonizing methodologies, this work illuminates the power dynamics embedded in my family stories and indigenous stories and histories are central to the work. I create a factionalized script drawing on data generated through my critical family history research to provide a coherent story and generate the conditions for deep emotional understandings.
Ex Vivo and In Vivo Noninvasive Imaging of Epidermal Growth Factor Receptor Inhibition on Colon Tumorigenesis Using Activatable Near-Infrared Fluorescent Probes
Authors: Ding Shengli , Blue Randall E. , Moorefield Emily , Yuan Hong , Lund Pauline K.
Published: September 2017

Background:

Near-infrared fluorescence (NIRF) imaging combined with enzyme-activatable NIRF probes has yielded promising results in cancer detection.

Objective:

To test whether 3-dimensional (3-D) noninvasive in vivo NIRF imaging can detect effects of epidermal growth factor receptor (EGFR) inhibitor on both polypoid and flat tumor load in azoxymethane (AOM)-induced colon tumors or tumors in ApcMin/+ mice.

Methods:

The AOM-injected KK-HIJ mice received EGFR inhibitor diet or chow diet. These and ApcMin/+ mice were given cathepsin-activatable probes (ProSense 680) before imaging. In vivo imaging was performed using quantitative tomographic NIRF imaging. Ex vivo imaging and histologic examination were performed. Dual imaging by micro computed tomography (CT) and 3D NIRF imaging was used to verify tumor location.

Results:

Tumor load reduction by EGFR inhibition was detected ex vivo using cathepsin B probes. In vivo imaging revealed intense activation of probes only in large tumors. Dual imaging with microCT and 3D NIRF imaging improved tumor detection in vivo.

Conclusions:

The 3-D NIRF imaging with ProSense 680 can detect and quantify drug effects on colon tumors ex vivo. The NIRF imaging with ProSense 680 probe has limitations as a valid nonendoscopic method for intestinal tumor detection. Combing with other imaging modalities will improve the specificity and sensitivity of intestinal tumor detection in vivo.
Success in national level junior tennis: Tactical perspectives
Authors: Klaus Anne , Bradshaw Ryan , Young Warren , O’Brien Brendan , Zois James
Published: September 2017

Purpose

Point duration in competitive tennis is becoming shorter, highlighting a greater emphasis on performance of the first strokes of each point, in particular, the performance of the server.

Methods

Descriptive measures of the video-based analysis included stroke type, point outcome and stroke position of the first two strokes of the server (service and first shot) during 10 randomly selected sets of competition on hard court. All participants (male; n = 8) were of the age group 14 years and below and competed in national level events.

Results

The performance of the first serve is characterized by an “in-percentage” of 54.6% and an improved chance of winning the point (for the server) following a first serve (55.9%; P < 0.001) compared to a second serve (42.9%). The majority of stroke positions for first-shot winners were located in the central zone of the court (52.1%; P < 0.01). In comparison to the error rate of all examined strokes, we observed an increased error rate of the first shot (16.5% vs. 22.4%; P < 0.01).

Conclusion

Contrasting to professionals, juniors produce more first-serve errors and win fewer points directly via the serve. Success in junior tennis relies in minimizing errors within short rallies specifically on the first shot of the server. Coaches of national level junior tennis players should focus on strategies to optimize court position following the serve and service percentage to increase competitive success rate. To achieve this, the server should utilize the serve as a “set-up” tool, dictating the direction of the returner’s return of serve within the central zones of the court.
Clinical Psychology of Oral Health: The Link Between Teeth and Emotions
Authors: Settineri Salvatore , Rizzo Amelia , Liotta Marco , Mento Carmela
Published: September 2017

The effects of oral health conditions on physical and psychosocial dimensions have been a matter of interest for several authors over the last decades. Nevertheless, literature lacks studies that address the relationship between the oral health–related quality of life (OHRQoL) and emotions. The present study aimed to investigate the psychological impact of oral disorders on people’s emotional well-being, with a particular attention to gender and age differences. Two hundred twenty-nine dental patients in care at private dental clinics were individually tested. One hundred thirty of them were females (56.8%) and 99 males (43.2%), aged between 18 and 83 years ( M = 38.11; SD = 16.7). For the evaluation, the Profile of Mood States (POMS) and the Oral Health Impact Profile (OHIP-14) were used. Data were analyzed using Pearson’s correlations, the ANOVA, and the Kruskal–Wallis test. OHRQoL showed several correlations with all the emotions explored, overcoming the well-known relationship with anxiety and depression ( p < .05). The degree of OHRQoL produced differences on mood states, which could appear normal, moderately altered, or psychopathological ( p < .03). Furthermore, in different life stages, patients showed specific OHRQoL and emotions.
Etanercept-Induced Hypoglycemia in a Patient With Psoriatic Arthritis and Diabetes
Authors: Pfeifer Emily C. , Saxon David R , Janson Robert W
Published: September 2017

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis and inflammation involving the axial skeleton and/or peripheral joints. It is more likely to be associated with metabolic syndrome and diabetes when compared with other inflammatory arthritides. Tumor necrosis factor-α (TNF-α) is one of several cytokines often elevated in rheumatologic disorders including PsA and has also been found to be elevated in patients with obesity, metabolic syndrome, diabetes, and/or atherosclerotic disease. We describe the case of a patient with PsA as well as poorly controlled type 2 diabetes mellitus who experienced not only improvement in his psoriasis and arthritis with the anti-TNF-α agent etanercept but also recurrent hypoglycemia and significant improvement in hemoglobin A1c despite discontinuation of all conventional therapy for diabetes.
Fatal Pulmonary Embolism in the Setting of Immune Reconstitution Inflammatory Syndrome Attributed to Ovarian Tuberculosis
Authors: Ugalde Israel , Pirela Daniela , Lo Presti Saberio , Bilderback Molly , Pirela Andrés , Chan Joseph
Published: September 2017

In developed countries, tuberculosis remains a health care challenge due to human immunodeficiency virus (HIV) and immigration from endemic regions. The Centers for Disease Control and Prevention reported 9557 new cases in 2015, with extrapulmonary involvement in 20.2% of the cases. We present a 33-year-old woman from Cape Town, South Africa, who developed abdominal pain and fever while working on a cruise ship. She sought medical where she underwent computed tomography of her chest, abdomen, and pelvis with findings suggestive of pulmonary tuberculosis and an 8.9-cm pelvic mass. HIV testing was positive and the patient was started on antiretroviral therapy. Bronchoscopy confirmed the presence of acid-fast bacilli, and she was started on rifampin, isoniazid, pyrazinamide, and ethambutol. She remained persistently febrile, raising suspicion for immune reconstitution inflammatory syndrome. However, despite empiric antibiotics, the patient remained persistently febrile, tachycardic, and on day 10 of admission she went into ventricular fibrillation and expired. Autopsy revealed an occlusive thrombus in the left main pulmonary artery in addition to necrotizing granulomata in multiple organs and bilateral tubo-ovarian abscesses. Postmortem cultures for were positive for Mycobacterium tuberculosis, all consistent with disseminated Mycobacterium tuberculosis. Although previous reports underscore the association between tuberculosis and hypercoagulability, the exact mechanism remains unknown. In this article, we report a case of disseminated tuberculosis complicated by bilateral tubo-ovarian abscesses with fatal pulmonary thrombus formation.
Contextualizing Identity and Exclusion and the Unheard Voices of Kolkata’s Migrant Hand-rickshaw-pullers
Authors: Bagchi Subrata
Published: September 2017

The intrigues of global capital are certain to drive out thousands of atrociously marginalized Dalit and Muslim hand-rickshaw-pullers from their livelihood in Kolkata (previously Calcutta) on the ground that not only are hand-rickshaws outdated, but their plying on the city-roads is an indication of retrogression as well as antithetical to development while global capital needs fast-paced smart-cities, supportive to unhindered capitalist development. In line with such exclusionary course of action, the State intends to rule out their continuance which would evict those marginal people from their livelihood. But this is utterly in contrast with the policy of inclusive growth. The plan is likely to play havoc with their livelihood since most of the pullers, belonging to the Hindi-and Urdu-speaking Dalit and Muslim groups are unskilled and old-aged. How would they survive when the government imposes overall ban on the hand-rickshaws, only to be replaced by motorized vehicles. Amidst the controversies, the vulnerable rickshaw-pullers meekly raise their voice of protest. But their voice fails to reach the portals of power.
Adaptive stabilization forQ-compensated reverse time migration
Authors: Wang Yufeng , Zhou Hui , Chen Hanming , Chen Yangkang
Published: September 2017

Reverse time migration (RTM) for attenuating media should take amplitude compensation and phase correction into consideration. However, attenuation compensation during seismic propagation suffers from numerical instability because of the boosted high-frequency ambient noise. We have developed a novel adaptive stabilization method for [Formula: see text]-compensated RTM ([Formula: see text]-RTM), which exhibits superior properties of time variance and [Formula: see text] dependence over conventional low-pass filtering-based method. We derive the stabilization operator by first analytically deriving [Formula: see text]-space Green’s functions for a constant-[Formula: see text] wave equation with decoupled fractional Laplacians and its compensated equation. The time propagator of Green’s function for the viscoacoustic wave equation decreases exponentially, whereas that of the compensated equation is exponentially divergent at a high wavenumber, and it is not stable after the wave is extrapolated for a long time. Therefore, the Green’s functions theoretically explain how the numerical instability existing in [Formula: see text]-RTM arises and shed light on how to overcome this problem pertinently. The stabilization factor required in the proposed method can be explicitly identified by the specified gain limit according to an empirical formula. The [Formula: see text]-RTM results for noise-free data using low-pass filtering and adaptive stabilization are compared over a simple five-layer model and the BP gas chimney model to verify the superiority of the proposed approach in terms of fidelity and stability. The [Formula: see text]-RTM result for noisy data from the BP gas chimney model further demonstrates that our method enjoys a better antinoise performance and helps significantly to enhance the resolution of seismic images.
From Ergodic to Region- and Site-Specific Probabilistic Seismic Hazard Assessment: Method Development and Application at European and Middle Eastern Sites
Authors: Kotha Sreeram Reddy , Bindi Dino , Cotton Fabrice
Published: September 2017

The increasing numbers of recordings at individual sites allows quantification of empirical linear site-response adjustment factors ( δS2 S s) from the ground motion prediction equation (GMPE) residuals. The δS2 S s are then used to linearly scale the ergodic GMPE predictions to obtain site-specific ground motion predictions in a partially non-ergodic Probabilistic Seismic Hazard Assessment (PSHA). To address key statistical and conceptual issues in the current practice, we introduce a novel empirical region- and site-specific PSHA methodology wherein, (1) site-to-site variability ( φ S2 S) is first estimated as a random-variance in a mixed-effects GMPE regression, (2) δS2 S s at new sites with strong motion are estimated using the a priori φ S2 S, and (3) the GMPE site-specific single-site aleatory variability σ ss,s is replaced with a generic site-corrected aleatory variability σ0. Comparison of region- and site-specific hazard curves from our method against the traditional ergodic estimates at 225 sites in Europe and Middle East shows an approximate 50% difference in predicted ground motions over a range of hazard levels—a strong motivation to increase seismological monitoring of critical facilities and enrich regional ground motion data sets.
Site-Corrected Magnitude- and Region-Dependent Correlations of Horizontal Peak Spectral Amplitudes
Authors: Kotha Sreeram Reddy , Bindi Dino , Cotton Fabrice
Published: September 2017

Empirical correlations of horizontal peak spectral amplitudes (PSA) are modeled using the total-residuals obtained in a ground motion prediction equation (GMPE) regression. Recent GMPEs moved toward partially non-ergodic region- and site-specific predictions, while the residual correlation models remained largely ergodic. Using mixed-effects regression, we decompose the total-residuals of a pan-European GMPE into between-event, between-site, and event-and-site corrected residuals to investigate the ergodicity in empirical PSA correlations. We first observed that the between-event correlations are magnitude-dependent, partially due to the differences in source spectra, and influence of stress-drop parameter on small and large events. Next, removing the between-site residuals from within-event residuals yields the event-and-site corrected residuals which are found to be region-dependent, possibly due to the regional differences in distance-decay of short period PSAs. Using our site-corrected magnitude- and region-dependent correlations, and the between-site residuals as empirical site-specific ground motion adjustments, we compute partially non-ergodic conditional mean spectra at four well-recorded sites in Europe and Middle Eastern regions. 09_EERI_33_4_Suppl_ES1_Online.xlsx
Changes in Insurance Coverage and Stage at Diagnosis Among Nonelderly Patients With Cancer After the Affordable Care Act
Authors: Jemal Ahmedin , Lin Chun Chieh , Davidoff Amy J. , Han Xuesong
Published: September 2017

Purpose

To examine change in the percent uninsured and early-stage diagnosis among nonelderly patients with newly diagnosed cancer after the Affordable Care Act (ACA).

Patients and Methods

By using the National Cancer Data Base, we estimated absolute change (APC) and relative change in percent uninsured among patients with newly diagnosed cancer age 18 to 64 years between 2011 to the third quarter of 2013 (pre-ACA implementation) and the second to fourth quarter of 2014 (post-ACA) in Medicaid expansion and nonexpansion states by family income level. We also examined demographics-adjusted difference in differences in APC between Medicaid expansion and nonexpansion states. We similarly examined changes in insurance and early-stage diagnosis for the 15 leading cancers in men and women (top 17 cancers total).

Results

Between the pre-ACA and post-ACA periods, percent uninsured among patients with newly diagnosed cancer decreased in all income categories in both Medicaid expansion and nonexpansion states. However, the decrease was largest in low-income patients who resided in expansion states (9.6% to 3.6%; APC, −6.0%; 95% CI, −6.5% to −5.5%) versus their counterparts who resided in nonexpansion states (14.7% to 13.3%; APC, −1.4%; 95% CI, −2.0% to −0.7%), with an adjusted difference in differences of −3.3 (95% CI, −4.0 to −2.5). By cancer type, the largest decrease in percent uninsured occurred in patients with smoking- or infection-related cancers. A small but statistically significant shift was found toward early-stage diagnosis for colorectal, lung, female breast, and pancreatic cancer and melanoma in patients who resided in expansion states.

Conclusion

Percent uninsured among nonelderly patients with newly diagnosed cancer declined substantially after the ACA, especially among low-income people who resided in Medicaid expansion states. A trend toward early-stage diagnosis for select cancers in expansion states also was found. These results reinforce the importance of policies directed at providing affordable coverage to low-income, vulnerable populations.
Leverage of an Existing Cervical Cancer Prevention Service Platform to Initiate Breast Cancer Control Services in Zambia: Experiences and Early Outcomes
Authors: Pinder Leeya F. , Henry-Tillman Ronda , Linyama David , Kusweje Victor , Nzayisenga Jean-Baptiste , Shibemba Aaron , Sahasrabuddhe Vikrant , Lishimpi Kennedy , Mwanahamuntu Mulindi , Hicks Michael , Parham Groesbeck P.
Published: September 2017

Purpose

In 2005, the Cervical Cancer Prevention Program in Zambia (CCPPZ) was implemented and has since provided cervical cancer screen-and-treat services to more than 500,000 women. By leveraging the successes and experiences of the CCPPZ, we intended to build capacity for the early detection and surgical treatment of breast cancer.

Methods

Our initiative sought to build capacity for breast cancer care through the (1) formation of a breast cancer advocacy alliance to raise awareness, (2) creation of resource-appropriate breast cancer care training curricula for mid- and high-level providers, and (3) implementation of early detection and treatment capacity within two major health care facilities.

Results

Six months after the completion of the initiative, the following outcomes were documented: Breast health education and clinical breast examination (CBE) services were successfully integrated into the service platforms of four CCPPZ clinics. Two new breast diagnostic centers were opened, which provided access to breast ultrasound, ultrasound-guided core needle biopsy, and needle aspiration. Breast health education and CBE were provided to 1,955 clients, 167 of whom were evaluated at the two diagnostic centers; 55 of those evaluated underwent core-needle biopsy, of which 17 were diagnosed with invasive cancer. Newly trained surgeons performed six sentinel lymph node mappings, eight sentinel lymph node dissections, and 10 breast conservation surgeries (lumpectomies).

Conclusion

This initiative successfully established clinical services in Zambia that are critical for the early detection and surgical management of breast cancer.
Quantitative analysis of mechanical force required for cell extrusion in zebrafish embryonic epithelia
Authors: Yamada Sohei , Iino Takanori , Bessho Yasumasa , Hosokawa Yoichiro , Matsui Takaaki
Published: September 2017

When cells in epithelial sheets are damaged by intrinsic or extrinsic causes, they are eliminated by extrusion from the sheet. Cell extrusion, which is required for maintenance of tissue integrity, is the consequence of contraction of actomyosin rings, as demonstrated by both molecular/cell biological experimentation and numerical simulation. However, quantitative evaluation of actomyosin contraction has not been performed because of the lack of a suitable direct measurement system. In this study, we developed a new method using a femtosecond laser to quantify the contraction force of the actomyosin ring during cell extrusion in zebrafish embryonic epithelia. In this system, an epithelial cell in zebrafish embryo is first damaged by direct femtosecond laser irradiation. Next, a femtosecond laser-induced impulsive force is loaded onto the actomyosin ring, and the contraction force is quantified to be on the order of kPa as a unit of pressure. We found that cell extrusion was delayed when the contraction force was slightly attenuated, suggesting that a relatively small force is sufficient to drive cell extrusion. Thus, our method is suitable for the relative quantitative evaluation of mechanical dynamics in the process of cell extrusion, and in principle the method is applicable to similar phenomena in different tissues and organs of various species.
Influence of a GSK3β phosphorylation site within the proximal C-terminus of neurofilament-H on neurofilament dynamics
Authors: Vohnoutka Rishel Brenna , Boumil Edward F. , Liu Yuguan , Uchida Atsuko , Pant Harish C. , Shea Thomas B.
Published: September 2017

Phosphorylation of the C-terminal tail of the heavy neurofilament subunit (NF-H) impacts NF axonal transport and residence within axons by fostering NF-NF associations that compete with transport. We tested the role of phosphorylation of a GSK-3β consensus site (S493) located in the proximal portion of the NF-H tail, in NF dynamics by transfection of NB2a/d1 cells with NF-H where S493 was mutated to aspartic acid (S493D) or to alanine (S493A) to mimic constitutive phosphorylation and non-phosphorylation. S493D underwent increased transport into axonal neurites, while S493A displayed increased perikaryal NF aggregates that were decorated by anti-kinesin. Increased levels of S493A co-precipitated with anti-kinesin indicating that reduced transport of S493A was not due to reduced kinesin association but due to premature NF-NF interactions within perikarya. S493D displayed increased phospho-immunoreactivity within axonal neurites at downstream C-terminal sites attributable to mitogen-activated protein kinase and cyclin-dependent kinase 5. However, S493D was more prone to proteolysis following kinase inhibition, suggesting that S493 phosphorylation is an early event that alters sidearm configuration in a manner that promotes appropriate NF distribution. We propose a novel model for sidearm configuration.
RhoB blockade selectively inhibits autoantibody production in autoimmune models of rheumatoid arthritis and lupus
Authors: Mandik-Nayak Laura , DuHadaway James B. , Mulgrew Jennifer , Pigott Elizabeth , Manley Kaylend , Sedano Summer , Prendergast George C. , Laury-Kleintop Lisa D.
Published: September 2017

During the development of autoimmune disease, a switch occurs in the antibody repertoire of B cells favoring the production of pathogenic versus non-pathogenic autoantibodies. However, there is limited knowledge concerning how this pivotal step occurs. Here we present genetic and pharmacological evidence of a positive modifier function for the vesicular small GTPase RhoB in specifically mediating the generation of pathogenic autoantibodies and disease progression in the K/BxN preclinical model of inflammatory arthritis. Genetic deletion of RhoB abolished the production of pathogenic autoantibodies and ablated joint inflammation in the model. In like manner, administration of a novel RhoB-targeted monoclonal antibody was sufficient to ablate autoantibody production and joint inflammation. In the MRL/lpr mouse model of systemic lupus erythematosus (SLE), another established preclinical model of autoimmune disease associated with autoantibody production, administration of the anti-RhoB antibody also reduced serum levels of anti-dsDNA antibodies. Notably, the therapeutic effects of RhoB blockade reflected a selective deficiency in response to self antigens, insofar as RhoB-deficient mice and mice treated with anti-RhoB Ig both mounted comparable productive antibody responses after immunization with a model foreign antigen. Overall, our results highlight a novel function for RhoB in supporting the specific production of pathogenic autoantibodies, and offer a preclinical proof of concept for use of anti-RhoB Ig as a disease-selective therapy to treat autoimmune disorders driven by pathogenic autoantibodies.
Renal scar formation and kidney function following antibiotic-treated murine pyelonephritis
Authors: Olson Patrick D. , McLellan Lisa K. , Liu Alice , Briden Kelleigh L. , Tiemann Kristin M. , Daugherty Allyssa L. , Hruska Keith A. , Hunstad David A.
Published: September 2017

We present a new preclinical model to study treatment, resolution, and sequelae of severe ascending pyelonephritis. Urinary tract infection (UTI), primarily caused by uropathogenic Escherichia coli (UPEC), is a common disease in children. Severe pyelonephritis is the primary cause of acquired renal scarring in childhood, which may eventually lead to hypertension and chronic kidney disease in a small but important fraction of patients. Preclinical modeling of UTI utilizes almost exclusively females, which (in most mouse strains) exhibit inherent resistance to severe ascending kidney infection; consequently, no existing preclinical model has assessed the consequences of recovery from pyelonephritis following antibiotic treatment. We recently published a novel mini-surgical bladder inoculation technique, with which male C3H/HeN mice develop robust ascending pyelonephritis, highly prevalent renal abscesses, and evidence of fibrosis. Here, we devised and optimized an antibiotic treatment strategy within this male model to more closely reflect the clinical course of pyelonephritis. A 5-day ceftriaxone regimen initiated at the onset of abscess development achieved resolution of bladder and kidney infection. A minority of treated mice displayed persistent histologic abscess at the end of treatment, despite microbiologic cure of pyelonephritis; a matching fraction of mice 1 month later exhibited renal scars featuring fibrosis and ongoing inflammatory infiltrates. Successful antibiotic treatment preserved renal function in almost all infected mice, as assessed by biochemical markers 1 and 5 months post treatment; hydronephrosis was observed as a late effect of treated pyelonephritis. An occasional mouse developed chronic kidney disease, generally reflecting the incidence of this late sequela in humans. In total, this model offers a platform to study the molecular pathogenesis of pyelonephritis, response to antibiotic therapy, and emergence of sequelae including fibrosis and renal scarring. Future studies in this system may inform adjunctive therapies that may reduce the long-term complications of this very common bacterial infection.
Integrin α8 and Pcdh15 act as a complex to regulate cilia biogenesis in sensory cells
Authors: Goodman Linda , Zallocchi Marisa
Published: September 2017

The way an organism perceives its surroundings depends on sensory systems and the highly specialized cilia present in the neurosensory cells. Here, we describe the existence of an integrin α8 (Itga8) and protocadherin-15a (Pcdh15a) ciliary complex in neuromast hair cells in a zebrafish model. Depletion of the complex via downregulation or loss-of-function mutation leads to a dysregulation of cilia biogenesis and endocytosis. At the molecular level, removal of the complex blocks the access of Rab8a into the cilia as well as normal recruitment of ciliary cargo by centriolar satellites. These defects can be reversed by the introduction of a constitutively active form of Rhoa, suggesting that Itga8–Pcdh15a complex mediates its effect through the activation of this small GTPase and probably by the regulation of actin cytoskeleton dynamics. Our data points to a novel mechanism involved in the regulation of sensory cilia development, with the corresponding implications for normal sensory function.
Lipopolysaccharide modulates p300 and Sirt1 to promote PRMT1 stability via an SCFFbxl17-recognized acetyldegron
Authors: Lai Yandong , Li Jin , Li Xiuying , Zou Chunbin
Published: September 2017

E3 ubiquitin ligase recognizes its protein substrates via specific molecular signatures for ubiquitin proteasomal degradation. However, the role of acetylation/deacetylation in the process of E3 ubiquitin ligase recognizing its protein substrates is not fully studied. Here, we report that a tandem IK motif in protein arginine methyltransferase 1 (PRMT1) forms an acetyldegron to recruit the F-box/LRR-repeat protein 17 (FBXL17), a component of the SKP1–CUL1–F-box protein (SCF)-type E3 ubiquitin ligase complex. PRMT1 is polyubiquitylated for proteasome degradation with a half-life of approximately 4 h in lung epithelial cells. SCFFbxl17 mediates PRMT1 polyubiquitylation at K117. SCFFbxl17 specifically binds PRMT1 via a unique motif IKxxxIK. Strikingly, the acetylation/deacetylation status of the lysine residues within the motif determines Fbxl17 binding. Deacetylation on both K200 and K205 by Sirtuin 1 (Sirt1) and acetylation of p300 (EP300) on K205 collaboratively prepare the motif for SCFFbxl17 binding thereby triggering PRMT1 protein degradation. Pathogen-derived lipopolysaccharide (LPS) downregulates Sirt1 and p300 to protect PRMT1 from degradation. This study demonstrates that LPS promotes PRMT1 stability by blockade of PRMT1 and SCFFbxl17 binding via an acetylation/deacetylation-modified acetyldegron; and LPS-elevated levels of PRMT1 lead to bronchial epithelial cell overgrowth in pulmonary inflammatory diseases.
COG7 deficiency in Drosophila generates multifaceted developmental, behavioral and protein glycosylation phenotypes
Authors: Frappaolo Anna , Sechi Stefano , Kumagai Tadahiro , Robinson Sarah , Fraschini Roberta , Karimpour-Ghahnavieh Angela , Belloni Giorgio , Piergentili Roberto , Tiemeyer Katherine H. , Tiemeyer Michael , Giansanti Maria Grazia
Published: September 2017

Congenital disorders of glycosylation (CDG) comprise a family of human multisystemic diseases caused by recessive mutations in genes required for protein N-glycosylation. More than 100 distinct forms of CDGs have been identified and most of them cause severe neurological impairment. The Conserved Oligomeric Golgi (COG) complex mediates tethering of vesicles carrying glycosylation enzymes across the Golgi cisternae. Mutations affecting human COG1, COG2 and COG4–COG8 cause monogenic forms of inherited, autosomal recessive CDGs. We have generated a Drosophila COG7-CDG model that closely parallels the pathological characteristics of COG7-CDG patients, including pronounced neuromotor defects associated with altered N-glycome profiles. Consistent with these alterations, larval neuromuscular junctions of Cog7 mutants exhibit a significant reduction in bouton numbers. We demonstrate that the COG complex cooperates with Rab1 and Golgi phosphoprotein 3 to regulate Golgi trafficking and that overexpression of Rab1 can rescue the cytokinesis and locomotor defects associated with loss of Cog7. Our results suggest that the Drosophila COG7-CDG model can be used to test novel potential therapeutic strategies by modulating trafficking pathways.
Humeral loads during swimming and walking in turtles: implications for morphological change during aquatic reinvasions
Authors: Young Vanessa K Hilliard , Wienands Charlotte E. , Wilburn Brittany P. , Blob Richard W.
Published: September 2017

During evolutionary reinvasions of water by terrestrial vertebrates, ancestrally tubular limb bones often flatten to form flippers. Differences in skeletal loading between land and water might have facilitated such changes. In turtles, femoral shear strains are significantly lower during swimming than during walking, potentially allowing a release from loads favoring tubular shafts. However, flipper-like morphology in specialized tetrapod swimmers is most accentuated in the forelimbs. To test if the forelimbs of turtles also experience reduced torsional loading in water, we compared strains on the humerus of river cooters (Pseudemys concinna) between swimming and terrestrial walking. Humeral shear strains are also lower during swimming compared to terrestrial walking; however, this appears to relate to reduction in overall strain magnitudes, rather than a specific reduction in twisting. These results indicate that shear strains show similar reductions between swimming and walking for forelimb and hindlimb, but these reductions are produced through different mechanisms.
Fibromax-based nonalcoholic fatty liver disease in chronic obstructive pulmonary disease patients with obstructive sleep apnea: Methodological considerations
Authors: Monneret Denis
Published: September 2017

The relationship between nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) has been well demonstrated, but remains to be evidenced in chronic obstructive pulmonary disease (COPD). Recently, Viglino et al. (Eur Respir J, 2017) attempted to determine the prevalence of liver fibrosis, steatosis and nonalcoholic steatohepatitis (NASH) in COPD patients, some of whom had OSA, basing the NAFLD diagnostic on three circulating biomarker-based liver scores: the FibroTest, SteatoTest and NashTest, from the Fibromax® panel. Among the main findings, the absence of OSA treatment emerged as independently associated with liver fibrosis and steatosis, when compared to effective treatment. However, besides the low number of treated patients, no polysomnographic respiratory data was provided, making it difficult to differentiate the impact of OSA from that of COPD in NAFLD prevalence. Furthermore, NAFLD diagnosis relied exclusively on circulating biomarker-based liver scores, without histological, imagery or other liver exploratory methods. Therefore, in this article, some methodological points are reminded and discussed, including the choice of OSA measurements, and the significance of ActiTest and AshTest scores from Fibromax® in this pathophysiological context.
Achieving prescribing competencies
Authors: Lowery-Brady Hannah
Published: September 2017

To gain the independent and supplementary prescribing qualification, it is essential to meet the competencies within the ‘Single Competency Framework’ for prescribers and the professional standards set out by the Nursing and Midwifery Council (NMC). The NMC are currently reviewing the ‘Standards of Proficiency for Nurse and Midwife Prescribers’ and are looking to move to using the Royal Pharmaceutical Society's ‘Single Competency Framework’.

There is limited literature and guidance available to support the use of the competencies for prescribing. Relevant sources of information that were found useful for assisting prescribing practice have been identified.

Reflections on how each competency has been achieved and how this has been evidenced are discussed. This includes reflective practice, supervised practice and case studies, which are identified as essential for achieving competence in prescribing.