bluuebunny/crossref_metadata_2025 huggingface dataset:
The Transformation of Suffering in Paul of the Cross, Lonergan and Buddhism
Authors: Dadosky John D.
Published: May 2015

This paper explores St. Paul of the Cross's passion-centred spirituality as a context for avoiding the distortions of such spirituality and promoting proper praxis. These distortions are not the legacy of Paul of the Cross himself, but the fact that his contemplation of the passion was primarily performative and mystical, along with the lack of a systematic theology on the passion-death-and resurrection, there remains a context wherein distortions of passion-centred approaches can occur. The paper then presents some aspects of Bernard Lonergan's thought on lex crucis and also from his Trinitarian work in order to provide a theological framework (orthotheoria). This framework can help prevent the distortions of such a passion-centred spirituality and guide orthopraxis of passion-centred spiritualities. In the final section we explore some insights from Buddhism that are consonant with both Paul of the Cross's spirituality and Lonergan's law of the cross as fruits of the Spirit and seeds of the Word.
Extracapillary proliferation is an independent predictive factor in Immunoglobulin A nephropathy
Authors: Serriello Ilaria , Polci Rosaria , Feriozzi Sandro , Gigante Antonietta , Di Giulio Salvatore , Rosa Margherita , Galliani Marco , Morosetti Massimo , Pugliese Francesco , Petitti Tommasangelo , Onetti Muda Andrea , Giannakakis Konstantinos
Published: May 2015

Background

Oxford classification of Immunoglobulin A Nephropathy (IgAN) identifies four pathological features as predictors of renal outcome (MEST‐score): mesangial proliferation (M); endocapillary proliferation (E); segmental glomerulosclerosis (S); tubular atrophy/interstitial fibrosis (T). In particular extracapillary proliferation (Ex) was not considered as an independent histological variable predicting renal outcome. Recently the VALIGA study provided a validation of the Oxford classification in a large European cohort of IgAN patients and re‐stated that Ex is not associated with a worse renal prognosis. We propose a retrospective study to evaluate the predictive value of the MEST‐score in a multi‐centre, single region group of patients from central Italy and in addition, to investigate Ex as a marker predicting renal outcome.

Methods

One hundred and seven patients were enrolled in this study. Clinical data of each patient were available at diagnosis and follow‐up. The median age at diagnosis was 36.7 years; 72% of the patients were males. Histological parameters were those included in the MEST‐score of the Oxford classification; in addition, Ex was also assessed.

Results

Multiple linear regression models for survey were used. Statistical analysis showed a correlation between the progression of renal decline, in terms of estimated glomerular filtration rate (slope eGFR), and M, S, T. Differently from Oxford and VALIGA studies, no correlation was found with E, while Ex correlated with a decline of eGFR.

Conclusions

Our results suggest that Ex represents an additional independent variable associated with a faster decline of renal function in IgAN.
Pit membrane structure is highly variable and accounts for a major resistance to water flow through tracheid pits in stems and roots of two boreal conifer species
Authors: Schulte Paul J. , Hacke Uwe G. , Schoonmaker Amanda L.
Published: May 2015

The flow of xylem sap in conifers is strongly dependent on the presence of a low resistance path through bordered pits, particularly through the pores present in the margo of the pit membrane.

A computational fluid dynamics approach was taken, solving the Navier–Stokes equation for models based on the geometry of pits observed in tracheids from stems and roots of Picea mariana (black spruce) and Picea glauca (white spruce).

Model solutions demonstrate a close, inverse relationship between the total resistance of bordered pits and the total area of margo pores. Flow through the margo was dominated by a small number of the widest pores. Particularly for pits where the margo component of flow resistance was low relative to that of the torus, pore location near the inner edge of the margo allowed for greater flow than that occurring through similar‐sized pores near the outer edge of the margo.

Results indicate a surprisingly large variation in pit structure and flow characteristics. Nonetheless, pits in roots have lower resistance to flow than those in stems because the pits were wider and consisted of a margo with a larger area in pores.
Z‐plasty for closure of moderately sized oral defects – a case report
Authors: Weinstock R.J. , Clarkson E.I.
Published: May 2015

Following sharp excision of oral pathology, management of the residual defect is often a quandary. The oral mucosa can often be extensively undermined; however, in some instances, primary closure with local advancement is not desirable because of the potential to distort adjacent anatomy. In such circumstances, alternative treatment options include healing via secondary or tertiary intention. In this article, we present a 79 year‐old female who underwent sharp excision of an epulis fissuratum from the left maxillary labial mucosa resulting in a 3.5 cm oral defect. Using a Z‐plasty transposition flap, closure was achieved without distortion of adjacent anatomy.
Is immunoglobulin E to Staphylococcus aureus enterotoxins associated with asthma at 20 years?
Authors: Sintobin Ina , Keil Thomas , Lau Susanne , Grabenhenrich Linus , Holtappels Gabriele , Reich Andreas , Wahn Ulrich , Bachert Claus
Published: May 2015

Background

In adults, subjects sensitized to Staphylococcus aureus enterotoxins (SE) seem to have an increased risk of asthma, whereas this association is less clear in childhood and adolescence. The primary aim of the present analysis was to examine the association between sensitization to SE and asthma at the age of 20 years.

Methods

The German Multicentre Allergy Study recruited 1314 healthy newborns in 1990. We analyzed data from 61 asthmatics (based on at least two criteria: physician diagnosed asthma ever, wheezing in the last 12 months, asthma medication in the last 12 months) and 122 healthy study participants at age 20. In serum, specific Immunoglobulin E (IgE) to SE and common aeroallergens were measured. The association between asthma at age 20 and sensitization to SE was estimated by logistic regression models considering allergic, socio‐demographic, and lifestyle factors as potential confounders.

Results

Fifty‐five percent of the included participants were female. At age 20, subjects sensitized to SE were more likely to have asthma than not‐sensitized subjects: raw odds ratio (OR) 2.5, 95%‐confidence interval (95%CI) [1.3‐4.7]; adjusted OR 1.6, 95%CI [0.8‐3.4].

Conclusion

Asthmatics at age 20 were more often sensitized to SE compared to controls. Our study may indicate a moderate relationship between SE‐sensitization and asthma; however, this association attenuated after adjusting for potential confounders and was no longer statistically significant. Longitudinal investigations with SE‐IgE measurements at different time points in larger samples are needed to explore the temporal manner of this relationship.
Poorly differentiated hepatocellular carcinoma accompanied by anti‐Hu antibody‐positive paraneoplastic peripheral neuropathy
Authors: Matsui Takahiro , Hori Yumiko , Nagano Hiroaki , Eguchi Hidetoshi , Marubashi Shigeru , Wada Hiroshi , Wada Naoki , Ikeda Jun‐ichiro , Sakamoto Michiie , Morii Eiichi
Published: May 2015

The anti‐Hu antibody is one of the most famous onco‐neural antibodies related to paraneoplastic neurological syndrome, and is associated with small cell lung carcinoma in most cases. Here, we report a case of poorly differentiated hepatocellular carcinoma accompanied by paraneoplastic peripheral neuropathy positive for the anti‐Hu antibody. Image inspection before operation revealed that no tumors were found in organs other than the liver, including lung, and that the liver tumor had no metastatic lesion. The liver tumor showed histological appearance of poorly differentiated carcinoma with cartilaginous metaplasia and partial blastoid cell appearance. Most tumor cells presented trabecular‐like structure lined by sinusoidal vessels. Immunohistochemically, the tumor cells were positive for low molecular weight cytokeratin and vimentin, partially positive for cytokeratin 19 and CD56, but negative for synaptophysin, chromogranin A and alpha‐fetoprotein. Based on the trabecular‐like morphology and the results of immunohistochemical staining, we concluded that the tumor was diagnosed as poorly differentiated hepatocellular carcinoma. Anti‐Hu antibody‐positive paraneoplastic peripheral neuropathy accompanied with liver tumor is extremely rare as far as is known. The presented case indicates that poorly differentiated carcinoma has the potential to be the responsible lesion of anti‐Hu antibody‐positive paraneoplastic neurological syndrome and systemic work‐up is important for the management of this neurological disorder.
Pharmacology of Bisphosphonates in Patients with Chronic Kidney Disease
Authors: Ott Susan M.
Published: May 2015

Bisphosphonates are medications which bind strongly to mineral. They are ingested by osteoclasts and inhibit an enzyme necessary for bone resorption. The gastrointestinal absorption is poor and the only method of excretion is renal. Therefore, in patients with CKD the body accumulates a higher percentage of a dose of bisphosphonate. These medications remain attached to bone mineral for many years. Although the primary action is to inhibit bone resorption, secondarily bone formation is also inhibited, and in patients with CKD bisphosphonate use often leads to adynamic bone. In some experimental models in animals, the bisphosphonates can inhibit vascular calcification but this effect has not been seen in humans. Intravenous bisphosphonates may cause renal damage but oral doses do not reduce creatinine clearance. In stage 3 CKD, in patients who still have normal PTH, calcium, and alkaline phosphatase, randomized trials show similar benefits as in patients without CKD. Data from stage 4 and 5 CKD are very limited and no clear benefit has been shown.
Optimal PPS Sampling with Vanishing Auxiliary Variables – with Applications in Microscopy
Authors: Andersen Ina Trolle , Hahn Ute , Vedel Jensen Eva B.
Published: May 2015

Recently, non‐uniform sampling has been suggested in microscopy to increase efficiency. More precisely, proportional to size (PPS) sampling has been introduced, where the probability of sampling a unit in the population is proportional to the value of an auxiliary variable. In the microscopy application, the sampling units are fields of view, and the auxiliary variables are easily observed approximations to the variables of interest. Unfortunately, often some auxiliary variables vanish, that is, are zero‐valued. Consequently, part of the population is inaccessible in PPS sampling. We propose a modification of the design based on a stratification idea, for which an optimal solution can be found, using a model‐assisted approach. The new optimal design also applies to the case where ‘vanish’ refers to missing auxiliary variables and has independent interest in sampling theory. We verify robustness of the new approach by numerical results, and we use real data to illustrate the applicability.
Performance Management, Caseloads and the Frontline Provision of Social Services
Authors: van Berkel Rik , Knies Eva
Published: May 2015

Caseloads and performance management are important working conditions of workers delivering public social services in street‐level organizations. The literature on these working conditions argues that high caseloads and performance management have considerable consequences for workers' performance in terms of the quality of services they provide and the results they realize. This article empirically investigates and compares these consequences, drawing on the results of a quantitative study of frontline workers in 14 local welfare agencies in the Netherlands. These workers are responsible for the delivery of welfare‐to‐work policies to social assistance recipients. The findings show that high caseloads do, indeed, have a detrimental effect on workers' performance, whereas the impact of performance management is more modest, though confirming some of the findings reported in other studies on performance management. The results also show that by focusing service provision on a proportion of their caseload, workers are able to reduce the negative impact of high caseloads somewhat. Overall, the article finds that the negative impact of high caseloads is more pervasive than that of performance management. The article concludes that the recent focus in the literature on performance management and its consequences for public services should not turn scholars' attention away from the ‘traditional’ public administration problem of high caseload sizes.
What's in a Frame? How Professionals Assess Clients in Dutch Work Reintegration Practice
Authors: Eikenaar Teun , de Rijk Angelique E. , Meershoek Agnes
Published: May 2015

With the increased attention on labour market participation, the field of work reintegration support has grown dramatically. In order to improve professionals' performance, standards and performance measures are introduced in this field. We question whether this will improve the quality of their work. Closer scrutiny needs to be paid to the inherently normative and structuring role of professional judging. We applied the concept of ‘frames of reference’ to the process of professional judgement in work reintegration. This concept helped us to understand how a work reintegration professional structures a client's story through implicit rules that escape formalization and control mechanisms. On the basis of 24 in‐depth interviews with diverse work reintegration professionals in the Netherlands, we distinguish five of these frames: a procedural, a work‐focused, a caring, a learning and a facilitating frame of reference. Furthermore, we show that professionals differ widely in the images they have of clients, leading to a large variety in judgement of, and interaction with, clients. Though differences between professionals are inherent to a complex and dynamic field as work reintegration, the current variety in professional‐client contact in work reintegration seems to depend too much on arbitrary professional preferences. Therefore, reflection on these differences, both among professionals and by policymakers, is needed in order to improve the professional practice of work reintegration service.
Assessment of the FAO traditional land evaluation methods, A case study: Iranian Land Classification method
Authors: Bagheri Bodaghabadi M. , Martínez‐Casasnovas J. A. , Khakili P. , Masihabadi M. H. , Gandomkar A.
Published: May 2015

Land evaluation is a critical step in land‐use planning. Although many methods have been developed since the formulation of the FAO framework for land evaluation, several of the more traditional approaches still remain in widespread use but have not been adequately evaluated. Contrary to more recent land evaluation systems, which need considerable data, these systems only require basic soil and landscape information to provide a general view of land suitability for major types of land use. As the FAO initially presented its qualitative framework for land‐use planning, based on two previous methods developed in Iran and Brazil, in this study we assessed the reliability and accuracy of a traditional land evaluation method used in Iran, called land classification for irrigation (LCI), comparing its results with several qualitative and quantitative methods and actual yield values. The results showed that, although simpler than more recently developed methods, LCI provided reliable land suitability classes and also showed good relationships both with other methods analysed and with actual yields. Comparisons between qualitative and quantitative methods produced similar results for common crops (a barley–alfalfa–wheat–fallow rotation). However, these methods performed differently for opportunist crops (such as alfalfa) that are more dependent on income and market conditions than on land characteristics. In this work, we also suggest that using the FAO method to indicate LCI subclasses could help users or managers to recognize limitations for land‐use planning.
Ebola virus disease – gaps in knowledge and practice among healthcare workers in Lagos, August 2014
Authors: Oladimeji Abisola M. , Gidado Saheed , Nguku Patrick , Nwangwu Iruoma Genevieve , Patil Nikhil D. , Oladosu Femi , Roberts Alero Ann , Waziri Ndadilnasiya E. , Shuaib Faisal , Oguntimehin Olukayode , Musa Emmanuel , Nasidi Abdulsalami , Adewuyi Peter , Olayinka Adebola , Odubanjo Oladoyin ,   N‐FELTP Residents, Poggensee Gabriele
Published: May 2015

Objective

Healthcare workers (HCWs) play pivotal roles in outbreak responses. Ebola virus disease (EVD) outbreak spread to Lagos, Nigeria, in July 2014, infecting 11 HCWs (case fatality rate of 45%). This study was conducted during the outbreak to assess HCWs' EVD‐related knowledge and practices.

Methods

A health facility‐based cross‐sectional study was conducted among HCWs across Lagos State using stratified sampling technique. An interviewer‐administered questionnaire was administered to elicit respondents' socio‐demographic characteristics, knowledge and practices. A checklist assessing health facility's level of preparedness and HCWs' EVD‐related training was employed. HCWs' knowledge and practices were scored and classified as either good or poor. Multivariate analysis was performed with confidence interval set at 95%.

Results

A total of 112 health facilities with 637 HCWs were recruited. Mean age of respondents was 40.1 ± 10.9 years. Overall, 72.5% had good knowledge; doctors knew most. However, only 4.6% of HCWs reported good practices. 16.6% reported having been trained in identifying suspected EVD patient(s); 12.2% had a triaging area for febrile patients in their facilities. Higher proportions of HCWs with good knowledge and training reported good practices. HCWs with EVD‐related training were three times more likely to adopt good practices.

Conclusion

Lagos State HCWs had good knowledge of EVD without a corresponding level of good practices. Training was a predictor of good practices.
Lifestyle, attitudes and needs of uncured XDR‐TB patients living in the communities of South Africa: a qualitative study
Authors: Senthilingam Meera , Pietersen Elize , McNerney Ruth , te Riele Julian , Sedres Pat , Wilson Ruth , Dheda Keertan
Published: May 2015

Objective

Patient‐level data are required to inform strategies interrupting transmission and default in patients with extensively drug‐resistant TB (XDR‐TB) to improve models of care and identify potential routes of transmission. We therefore explored the experiences, lifestyle, attitudes and needs of patients with uncured XDR‐TB, who failed or interrupted therapy, living without treatment in the community.

Methods

We conducted in‐depth interviews with 12 community‐based patients from South Africa. Family members were interviewed when patients were unavailable. Interviews were analysed using inductive thematic analysis.

Results

The thematic experiences identified from the interviews were as follows: (i) living with but not being cured of XDR‐TB, (ii) altered lifestyle in the community, (iii) experiences with community health care, (iv) local community members, and (v) wants and needs. Patients identified mistrust in health care, futility of treatment regimens, a need for a purpose in life and subsistence as major concerns. Restriction of living in the community for patients whose treatment had failed resulted in self‐imposed isolation. Defaulters focused more on the never‐ending drug regimen and bad experiences with health care contributing to non‐adherence. Family members emphasised an under‐recognised experience of unforeseen burden, obligation, worry and discomfort. Lack of knowledge and lack of concern about transmission was evident.

Conclusion

Current models of care are not adequately meeting the needs of patients with uncured XDR‐TB and relatives. These data inform the need for community‐based palliative care, vocational facilities to improve economic opportunities, home‐based infection control and improved psychosocial support to increase patient adherence, reduce transmission, provide income and relieve the burden on family members.
Modelling chlorine residual decay as influenced by temperature
Authors: Monteiro Laura , Viegas Rui M.C. , Covas Dídia I.C. , Menaia José
Published: May 2015

Temperature is one of the most important factors affecting chlorine decay rates in drinking water systems. In this article, temperature effect on chlorine decay rates in raw and treated waters was studied. Results show that temperature affects differently the fast and slow decay phases, the latter being more sensitive to temperature variations, as higher values of the activation energy parameter were obtained. Accordingly, an improvement to the temperature dependent two reactant model (a parallel second order model), in which the activation energies of each decay phase are distinct, is proposed and successfully used for chlorine decay modelling. In waters from transport and distribution systems, however, the fast decay phase is mostly negligible. In such cases, a single phase second‐order model in which the activation energy parameter is given by the slow phase reaction, is likely to describe temperature effect on chlorine decay accurately.
Fast and accurate solution of inverse problem in optical scatterometry using heuristic search and robust correction
Authors: Zhu Jinlong , Jiang Hao , Shi Yating , Zhang Chuanwei , Chen Xiuguo , Liu Shiyuan
Published: May 2015

Library search is one of the most commonly used methods in optical scatterometry, which consists of the beforehand construction of a signature library and the grid search. The efficiency of existing search algorithms such as k-dimensional tree method and locality-sensitive hashing heavily depends on the size of the signature library and usually is inversely proportional to the library scale. Additionally, since the two-norm based objective function is quite sensitive to the outliers, the abnormally distributed measurement errors will bias the solution of the traditional chi-square or maximum likelihood function. In the present paper, the authors propose a heuristic search algorithm and a robust correction method to realize the fast library search and to achieve the more accurate results, respectively. Instead of searching in the signature library, the authors perform the search procedure in an extra constructed Jacobian library using the principle of gradient-based iteration algorithms, by which the fast search speed can be achieved for an arbitrary scale library. After the search, a robust correction procedure is performed on the basis of the searched optimal parameter set to obtain the more accurate results. Simulations and experiments performed on an etched silicon grating have demonstrated the feasibility of the proposed heuristic search algorithm and robust correction method.
Modeling blurring effects due to continuous gantry rotation: Application to region of interest tomography
Authors: Cant Jeroen , Palenstijn Willem Jan , Behiels Gert , Sijbers Jan
Published: May 2015

Purpose:

Projections acquired with continuous gantry rotation may suffer from blurring effects, depending on the rotation speed and the exposure time of each projection. This leads to blurred reconstructions if conventional reconstruction algorithms are applied. In this paper, the authors propose a reconstruction method for fast acquisitions based on a continuously moving and continuously emitting x‐ray source. They study the trade‐off between total acquisition time and reconstruction quality and compare with conventional reconstructions using projections acquired with a stepwise moving x‐ray source.

Methods:

The authors introduce the algebraic reconstruction technique with angular integration concept, which models the angular integration due to the relative motion of the x‐ray source during the projection.

Results:

Compared to conventional reconstruction from projections acquired with pulsed x‐ray emission, the proposed method results in substantially improved reconstruction quality around the center of rotation. Outside this region, the proposed method results in improved radial resolution and a decreased tangential resolution. For a fixed reconstruction quality of this region of interest, the proposed method enables a lower number of projections and thus a faster acquisition.

Conclusions:

The modeling of the continuous gantry rotation in the proposed method substantially improves the reconstruction quality in a region of interest around the rotation center. The proposed method shows potential for fast region of interest tomography.
Coping Strategies of Female Peer Leaders Participating in College Club Sports
Authors: Bryant Leigh A. , Clement Damien
Published: May 2015

Leadership positions on club sports teams can be valuable roles for undergraduate students, providing the opportunity to develop leadership skills, maintain healthy habits, build friendships, and foster organizational connections in the college setting. Nevertheless, involvement in club sports has the potential to create stress over and above the many demands that college students often experience. The purpose of this study was to identify and explore the ways in which female club sports peer leaders cope with perceived stress. Interviews were conducted with participants ( N = 7) using a semi-structured interview guide comprised of five questions grounded in the existing literature on stress and coping. The findings revealed that participants primarily used emotion-focused strategies to cope with stress; strategies such as seeking emotional social support and avoidance were used more frequently than seeking instrumental/information social support. Five specific coping strategies are examined and practical implications are discussed.
Examining Leadership Development through Student Leader Outdoor Recreation Training
Authors: Boettcher Michelle Lea , Gansemer-Topf Ann M.
Published: May 2015

Since their inception, student leadership development has been a consistent goal of outdoor recreation programs (ORPs). However, little research has been conducted to better understand how these experiences contribute to leadership development for college students. Using the Komives et al. (2005) model of leadership identity development, this qualitative research study examined leadership identity development in the context of a training trip for student employees of an ORP. By focusing on this particular training program, the study sought to answer the following research question: How does participating in an outdoor recreation training trip impact students' leadership identity development? The study found that the participants were navigating through the final three stages of Komives et al.'s (2005) leadership model: leadership differentiated, generativity, and integration/synthesis stages. Participants understood the role of positional leaders and that there were others who were able to lead without holding titles or positions; participants were able to articulate the role of leaders in helping others and sustaining the program; and participants also articulated how these experiences related to their lives beyond ORP trips, achieving the reflective goals of the integration and synthesis. The results highlight the importance of communication and teamwork in leadership development. The findings provide evidence of the role of ORP in enhancing student leadership identity and make the case for continued or expanded support for these programs. The findings of this study provide insight into how student leadership identity development takes place when students are involved in ORP experiences.
Benefits of Collegiate Recreational Sports Participation: Results from the 2013 NASPA Assessment and Knowledge Consortium Study
Authors: Forrester Scott
Published: May 2015

This study reports the results from the 2013 National Association of Student Personnel Administrators (NASPA) Assessment and Knowledge Consortium. Students ( N = 33,522) from 38 different colleges and universities across the United States completed the Recreation and Wellness Benchmark instrument. Using Astin's Theory of Student Involvement (1984), this study sought to determine if there were significant differences between different depth and breadth levels of participants' campus recreational sports involvement/participation on student retention, health and wellness, and student learning outcomes. Heavy Users placed significantly more importance on campus recreational sports facilities and programs when deciding to continue at their college/university, and felt they had increased or improved every health and wellness and student learning outcome from their participation in campus recreation significantly more when compared with Moderate, Light, and Non-Users. Findings from this nationwide study demonstrate the value of collegiate recreation to the college and university experience.
Nitrate sensing and uptake in
Arabidopsis
are enhanced by ABI2, a phosphatase inactivated by the stress hormone abscisic acid
Authors: Léran Sophie , Edel Kai H. , Pervent Marjorie , Hashimoto Kenji , Corratgé-Faillie Claire , Offenborn Jan Niklas , Tillard Pascal , Gojon Alain , Kudla Jörg , Lacombe Benoît
Published: May 2015

The phosphatase ABI2 enables plants to efficiently uptake and respond to changes in nitrogen availability.
Giving T cells the NOD
Authors: Foley John F.
Published: May 2015

The intracellular sensor NLRP12 inhibits inflammatory T cell responses and T cell–dependent diseases.
Uncrossing covalently linked DNA strands
Authors: Riddihough Guy
Published: May 2015

Surveying the battery of proteins required to repair covalently linked DNA strands reveals a new repair pathway.
Metabolic signals in the hypoxic response
Authors: Gough Nancy R.
Published: May 2015

NDRG3 binds to lactate produced in hypoxic cells and stimulates proliferation and angiogenesis.
Determination of Appropriate Weight-Based Cutoffs for Empiric Cefazolin Dosing Using Data from a Phase 1 Pharmacokinetics and Safety Study of Cefazolin Administered for Surgical Prophylaxis in Pediatric Patients Aged 10 to 12 Years
Authors: Schmitz Michael L. , Blumer Jeffrey L. , Cetnarowski Wes , Rubino Christopher M.
Published: May 2015

Despite over 40 years of worldwide usage, relatively few data have been published on the pharmacokinetics of cefazolin in pediatric surgical patients. The primary objectives of this study were to examine the pharmacokinetics and safety of cefazolin in children 10 to 12 years of age (inclusive) receiving 1 or 2 g of cefazolin, based on body weight. This multiple-center, open-label study enrolled pediatric patients electively scheduled for surgical procedures who required cefazolin as part of their routine clinical management. Patients weighing ≥25 to <50 kg received a 1-g dose, and patients weighing ≥50 to ≤85 kg received a 2-g dose. Postdose pharmacokinetic and safety assessments were conducted following drug administration. Cefazolin concentration-time data were analyzed by using both noncompartmental and population pharmacokinetics methods. Monte Carlo simulations were performed to identify appropriate weight-based cutoffs for the dosing of children aged 10 to 17 years of age. Twelve patients were enrolled in this study and provided the requisite pharmacokinetic data. In general, cefazolin was well tolerated. The mean cefazolin terminal elimination half-life, clearance, and area under the concentration-time curve from time zero to infinity in this population were 1.95 h, 0.804 ml/min/kg, and 607 mg · h/liter, respectively. Patients weighing 50 to 60 kg exhibited elevated cefazolin exposures. Observed pharmacokinetic parameters and simulation results indicated that a weight-based cutoff of 60 kg is predicted to provide cefazolin exposure consistent with that observed in normal, healthy adults at recommended doses for surgical prophylaxis. (This study has been registered at ClinicalTrials.gov under registration no. NCT01904357.)
A Sterilizing Tuberculosis Treatment Regimen Is Associated with Faster Clearance of Bacteria in Cavitary Lesions in Marmosets
Authors: Via Laura E. , England Kathleen , Weiner Danielle M. , Schimel Daniel , Zimmerman Matthew D. , Dayao Emmanuel , Chen Ray Y. , Dodd Lori E. , Richardson Mike , Robbins Katherine K. , Cai Ying , Hammoud Dima , Herscovitch Peter , Dartois Véronique , Flynn JoAnne L. , Barry Clifton E.
Published: May 2015

Shortening the lengthy treatment duration for tuberculosis patients is a major goal of current drug development efforts. The common marmoset develops human-like disease pathology and offers an attractive model to better understand the basis for relapse and test regimens for effective shorter duration therapy. We treated
Mycobacterium tuberculosis
-infected marmosets with two drug regimens known to differ in their relapse rates in human clinical trials: the standard four-drug combination of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) that has very low relapse rates and the combination of isoniazid and streptomycin that is associated with higher relapse rates. As early as 2 weeks, the more sterilizing regimen significantly reduced the volume of lung disease by computed tomography (
P
= 0.035) and also significantly reduced uptake of [
18
F]-2-fluoro-2-deoxyglucose by positron emission tomography (
P
= 0.049). After 6 weeks of therapy, both treatments caused similar reductions in granuloma bacterial load, but the more sterilizing, four-drug regimen caused greater reduction in bacterial load in cavitary lesions (
P
= 0.009). These findings, combined with the association in humans between cavitary disease and relapse, suggest that the basis for improved sterilizing activity of the four-drug combination is both its faster disease volume resolution and its stronger sterilizing effect on cavitary lesions. Definitive data from relapse experiments are needed to support this observation.
Splenic Retention of Plasmodium falciparum Gametocytes To Block the Transmission of Malaria
Authors: Duez Julien , Holleran John P. , Ndour Papa Alioune , Loganathan Sasdekumar , Amireault Pascal , Français Olivier , El Nemer Wassim , Le Pioufle Bruno , Amado Inês F. , Garcia Sylvie , Chartrel Nathalie , Le Van Kim Caroline , Lavazec Catherine , Avery Vicky M. , Buffet Pierre A.
Published: May 2015

Plasmodium falciparum
is transmitted from humans to
Anopheles
mosquito vectors via the sexual erythrocytic forms termed gametocytes. Erythrocyte filtration through microsphere layers (microsphiltration) had shown that circulating gametocytes are deformable. Compounds reducing gametocyte deformability would induce their splenic clearance, thus removing them from the blood circulation and blocking malaria transmission. The hand-made, single-sample prototype for microsphiltration was miniaturized to a 96-well microtiter plate format, and gametocyte retention in the microsphere filters was quantified by high-content imaging. The stiffening activity of 40 pharmacological compounds was assessed in microtiter plates, using a small molecule (calyculin) as a positive control. The stiffening activity of calyculin was assessed in spleen-mimetic microfluidic chips and in macrophage-depleted mice. Marked mechanical retention (80% to 90%) of mature gametocytes was obtained in microplates following exposure to calyculin at concentrations with no effect on parasite viability. Of the 40 compounds tested, including 20 antimalarials, only 5 endoperoxides significantly increased gametocyte retention (1.5- to 2.5-fold; 24 h of exposure at 1 μM). Mature gametocytes exposed to calyculin accumulated in microfluidic chips and were cleared from the circulation of macrophage-depleted mice as rapidly as heat-stiffened erythrocytes, thus confirming results obtained using the microsphiltration assay. An automated miniaturized approach to select compounds for their gametocyte-stiffening effect has been established. Stiffening induces gametocyte clearance both
in vitro
and
in vivo
. Based on physiologically validated tools, this screening cascade can identify novel compounds and uncover new targets to block malaria transmission. Innovative applications in hematology are also envisioned.
Anti-Pneumococcal Capsular Polysaccharide Antibody Response and CD5 B Lymphocyte Subsets
Authors: Moens Leen , Verbinnen Bert , Covens Kris , Wuyts Greet , Johnson Marina , Roalfe Lucy , Goldblatt David , Meyts Isabelle , Bossuyt Xavier
Published: May 2015

The role of CD19
+
CD5
+
and CD19
+
CD5
−
B cell subpopulations in the antibody response to pneumococcal capsular polysaccharides (caps-PSs) is controversial. In the present study, we evaluated the role of human CD19
+
CD5
+
and CD19
+
CD5
−
cell populations in the serotype-specific antibody response to caps-PS. After vaccination of 5 healthy human adults with Pneumovax (23-valent pneumococcal polysaccharide vaccine [PPV23]), IgG anti-caps-PS serotype 4 antibody-producing cells resided mainly in the CD19
+
CD5
−
B cell subset, as assessed by enzyme-linked immunosorbent spot (ELISpot) analysis. Moreover, in a humanized SCID mouse model, CD19
+
CD5
−
B cells were more effective than CD19
+
CD5
+
cells in producing IgG anti-cap-PS antibodies. Finally, an association was found between the level of IgG anti-caps-PS antibodies and the number of CD19
+
CD5
−
B cells in 33 humans vaccinated with PPV23. Taken together, our data suggest that CD5 defines a functionally distinct population of B cells in humans in the anti-caps-PS immune response.
Comparison of Models for Bubonic Plague Reveals Unique Pathogen Adaptations to the Dermis
Authors: Gonzalez Rodrigo J. , Weening Eric H. , Lane M. Chelsea , Miller Virginia L.
Published: May 2015

Vector-borne pathogens are inoculated in the skin of mammals, most likely in the dermis. Despite this, subcutaneous (s.c.) models of infection are broadly used in many fields, including
Yersinia pestis
pathogenesis. We expand on a previous report where we implemented intradermal (i.d.) inoculations to study bacterial dissemination during bubonic plague and compare this model with an s.c. model. We found that i.d. inoculations result in faster kinetics of infection and that bacterial dose influenced mouse survival after i.d. but not s.c. inoculation. Moreover, a deletion mutant of
rovA
, previously shown to be moderately attenuated in the s.c. model, was severely attenuated in the i.d. model. Lastly, based on previous observations where a population bottleneck from the skin to lymph nodes was observed after i.d., but not after s.c., inoculations, we used the latter model as a strategy to identify an additional bottleneck in bacterial dissemination from lymph nodes to the bloodstream. Our data indicate that the more biologically relevant i.d. model of bubonic plague differs significantly from the s.c. model in multiple aspects of infection. These findings reveal adaptations of
Y. pestis
to the dermis and how these adaptations can define the progression of disease. They also emphasize the importance of using a relevant route of infection when addressing host-pathogen interactions.
Infection of Interleukin 17 Receptor A-Deficient C3H Mice with Borrelia burgdorferi Does Not Affect Their Development of Lyme Arthritis and Carditis
Authors: Lasky Carrie E. , Jamison Kara E. , Sidelinger Darcie R. , Pratt Carmela L. , Zhang Guoquan , Brown Charles R.
Published: May 2015

Recently, a number of studies have reported the presence of interleukin 17 (IL-17) in patients with Lyme disease, and several murine studies have suggested a role for this cytokine in the development of Lyme arthritis. However, the role of IL-17 has not been studied using the experimental Lyme borreliosis model of infection of C3H mice with
Borrelia burgdorferi
. In the current study, we investigated the role of IL-17 in the development of experimental Lyme borreliosis by infecting C3H mice devoid of the common IL-17 receptor A subunit (IL-17RA) and thus deficient in most IL-17 signaling. Infection of both C3H and C3H IL-17RA
−/−
mice led to the production of high levels of IL-17 in the serum, low levels in the heart tissue, and no detectable IL-17 in the joint tissue. The development and severity of arthritis and carditis in the C3H IL-17RA
−/−
mice were similar to what was seen in wild-type C3H mice. In addition, development of antiborrelia antibodies and clearance of spirochetes from tissues were similar for the two mouse strains. These results demonstrate a limited role for IL-17 signaling through IL-17RA in the development of disease following infection of C3H mice with
B. burgdorferi
.
Interaction analysis of the new pooled cohort equations for 10-year atherosclerotic cardiovascular disease risk estimation: a simulation analysis
Authors: Schiros Chun G , Denney Thomas S , Gupta Himanshu
Published: May 2015

Objectives

To evaluate the individual and interacting impacts of the continuous variables (age, total cholesterol (total-C), high-density lipoprotein cholesterol (HDL-C) and systolic blood pressure(BP)) on 10-year atherosclerotic cardiovascular disease (ASCVD) risk and better understand the pattern of predicted 10-year risk with change of each variable using recently published new pooled cohort equations.

Design

Simulation analysis was performed across the whole range of the boundary limits suggested for the continuous variables for groupings based on race and gender in the pooled cohort 10-year risk equations.

Setting

Computer-based simulation analysis.

Participants

Data were generated by simulation using prespecified variable ranges.

Intervention

Data simulation and visual display of the hazard analysis.

Main outcome measures

Interactions of age with other variables were analysed using multidimensional visualisation and hazard analysis.

Results

In African–American females, due to the interaction of age with HDL-C, treated BP and untreated BP, increasing age may not always increase 10-year risk. Furthermore, in the same cohort, increasing HDL-C level may result in higher 10-year risk for older individuals. For Caucasian females, due to square of Ln (age) term in the equation, the age-risk curve does not monotonically increase with age. The vertex is within the given age range of 40–79 years for a certain range of total-C and HDL-C, indicating that age may not always result in increased predicted 10-year risk.

Conclusions

The new pooled cohort equations are sophisticated as they take into account the interactions of the continuous variables in predicting 10-year risk. We find situations where the estimated 10-year risk does not follow the general secular trends. The impact of such interesting patterns may be substantial and therefore further exploration is needed as it has direct implications in clinical management for primary prevention.
Disparities in the receipt of robot-assisted radical prostatectomy: between-hospital and within-hospital analysis using 2009–2011 California inpatient data
Authors: Kim Jungyoon , ElRayes Wael , Wilson Fernando , Su Dejun , Oleynikov Dmitry , Morien Marsha , Chen Li-Wu
Published: May 2015

Objectives

Despite the rapid proliferation of robot-assisted radical prostatectomy (RARP), little attention has been paid to patient utilisation of this newest surgical innovation and barriers that may result in disparities in access to RARP. The goal of this study is to identify demographic and economic factors that decrease the likelihood of patients with prostate cancer (PC) receiving RARP.

Design, setting and participants

A retrospective, pooled, cross-sectional study was conducted using 2009–2011 California State Inpatient Data and American Hospital Association data. Patients who were diagnosed with PC and underwent radical prostatectomy (RP) from 225 hospitals in California were identified, using ICD-9-CM diagnosis and procedure codes.

Primary outcome measures

Patients’ likelihood of receiving RARP was associated with patient and hospital characteristics using the two models: (1) between-hospital and (2) within-hospital models. Multivariate binomial logistic regression was used for both models. The first model predicted patient access to RARP-performing hospitals versus non-RARP-performing hospitals, after adjusting for patient and hospital-level covariates (between-hospital variation). The second model examined the likelihood of patients receiving RARP within RARP-performing hospitals (within-hospital variation).

Results

Among 20 411 patients who received RP, 13 750 (67.4%) received RARP, while 6661 (32.6%) received non-RARP. This study found significant differences in access to RARP-performing hospitals when race/ethnicity, income and insurance status were compared, after controlling for selected confounding factors (all p<0.001). For example, Hispanic, Medicare and Medicaid patients were more likely to be treated at non-RARP-performing hospitals versus RARP-performing hospitals. Within RARP-performing hospitals, Medicaid patients had 58% lower odds of receiving RARP versus non-RARP (adjusted OR 0.42, p<0.001). However, there were no significant differences by race/ethnicity or income within RARP-performing hospitals.

Conclusions

Significant differences exist by race/ethnicity and payer status in accessing RARP-performing hospitals. Furthermore, payer status continues to be an important predictor of receiving RARP within RARP-performing hospitals.
Diagnosed diabetes and premature death among middle-aged Japanese: results from a large-scale population-based cohort study in Japan (JPHC study)
Authors: Kato Masayuki , Noda Mitsuhiko , Mizoue Tetsuya , Goto Atsushi , Takahashi Yoshihiko , Matsushita Yumi , Nanri Akiko , Iso Hiroyasu , Inoue Manami , Sawada Norie , Tsugane Shoichiro
Published: May 2015

Objective

To examine the association between diabetes and premature death for Japanese general people.

Design

Prospective cohort study.

Setting

The Japan Public Health Center-based prospective study (JPHC study), data collected between 1990 and 2010.

Population

A total of 46 017 men and 53 567 women, aged 40–69 years at the beginning of baseline survey.

Main outcome measures

Overall and cause specific mortality. Cox proportional hazards models were used to calculate the HRs of all cause and cause specific mortality associated with diabetes.

Results

The median follow-up period was 17.8 years. During the follow-up period, 8223 men and 4640 women have died. Diabetes was associated with increased risk of death (856 men and 345 women; HR 1.60, (95% CI 1.49 to 1.71) for men and 1.98 (95% CI 1.77 to 2.21) for women). As for the cause of death, diabetes was associated with increased risk of death by circulatory diseases (HR 1.76 (95% CI 1.53 to 2.02) for men and 2.49 (95% CI 2.06 to 3.01) for women) while its association with the risk of cancer death was moderate (HR 1.25 (95% CI 1.11 to 1.42) for men and 1.04 (95% CI 0.82 to 1.32) for women). Diabetes was also associated with increased risk of death for ‘non-cancer, non-circulatory system disease’ (HR 1.91 (95% CI 1.71 to 2.14) for men and 2.67 (95% CI 2.25 to 3.17) for women).

Conclusions

Diabetes was associated with increased risk of death, especially the risk of death by circulatory diseases.