bluuebunny/crossref_metadata_2025 huggingface dataset:
Bicarbonate/Lactate Dialysis Solution Improves In Vivo Function of Peritoneal Host Defense in Rats
Authors: Pawlaczyk Krzysztof , Kuzlan-Pawlaczyk Malgorzata , Tobis Katarzyna Wieczorowska , Polubinska Alicja , Wisniewska Justyna , Faict Dirk , Holmes Cliff J. , Breborowicz Andrzej
Published: February 2020

Objective

To assess the in vivo peritoneal inflammatory reaction in rats dialyzed with neutral, bicarbonatelactate-buffered dialysis fluid.

Methods

Chronic peritoneal dialysis was performed for 4 weeks in Wistar rats with two solutions: (1) 40 mmol/l lactate-buffered fluid, pH 5.2, with a glucose concentration of 2.27 gldl (lac); and, (2) 15 mmolll lactate and 25 mmolll bicarbonate-buffered fluid, pH 7.0 -7.5, with a glucose concentration of 2.27gldl (Bic-lac). After 4 weeks, two peritoneal equilibration tests (PET 1 and PET 2) were performed in all animals with each respective solution. PET 1 was done with test solutions alone, whereas, on a subsequent day, PET 2 was performed with test solutions supplemented with endotoxin [lipopolysaccharide (IPS)] to induce peritonitis.

Results

During PET 1 no consistent differences were detected in peritoneal permeability between the lac and Bic-lac groups. Total dialysate cell count in the Bic-lac animals was lower than in rats treated with lac fluid: that is, at 8 hours, the respective counts were 1858 ± 524 cellslμl versus 2785 ± 1162 cellslμl (p < 0.01). Dialysate from animals dialyzed with Bic-lac contained more macrophages (at 4 hours: 53.6% ± 35.8% versus 35.8% ± 8.8%, p < 0.001) and fewer neutrophils (at 4 hours: 3.6% ± 1.8% versus 15.4%± 6.1%, p < 0.001) as compared to those dialyzed with the lac solution. Concentration of nitrites in 8-hour dwell dialysate samples from Bic-lac rats was lower than that in the lac group (0.98 ± 0.28 μmollml versus 2.32 ± 0.87 μmollml, p < 0.002), but cytokine levels in the dialysates were comparable. During PET 2, the in -crease in peritoneal permeability resulting from the lPS induced inflammatory response was similar for both test solutions. Dialysate cell count was higher in the lac group versus the Bic-lac group (at 8 hours: 8789 ± 4862 cellslμl versus 3961 ± 581 cellslμl, p < 0.001), contained more neutrophils (at 8 hours: 80.0% ± 11.3% versus 54.8% ± 4.4%, p < 0.001) and fewer macrophages (at 8 hours: 6.8% ± 5.6% versus 21.2% ± 3.3%, p < 0.05). During peritonitis, we found a higher overall dialysate concentration of both tumor necrosis factor (TNFα: +53%, p < 0.05) and of interferon gamma (lFN-y: +303%, p < 0.02), in the Bic-lac group than in the lac group.

Conclusions

A lower dialysate cell count, higher percentage of macrophages, and lower percentage of neutrophils in dialysate suggest that Bic-lac fluid induces a diminished nonspecific inflammatory response of the peritoneal cavity during dialysis. However, after in vivo stimulation, peritoneal cells from animals dialyzed with Bic-lac solution possess an augmented ability to produce inflammatory cytokines.
Nitric Oxide Production in Peritoneal Macrophages from Peritoneal Dialysis Patients with Bacterial Peritonitis
Authors: Plum Jörg , Tabatabaei Maryam Mirza , Lordnejad Mohammad Reza , Pipinika Olga , Razeghi Peter , Huang Chumnei , Meyer-Kirchrath Jutta , Grabensee Bernd
Published: February 2020

Nitric oxide (NO) is produced by various cell types, and it is an important mediator in many biological processes, including macrophage-mediated cellular host defense. The relevance and amount of NO production in peritonitis during peritoneal dialysis (PD) treatment is still not clear.

We studied whether human peritoneal macrophages (PMΦ) isolated from healthy PD patients or PD patients with peritonitis showed different spontaneous or lipo-polysaccharide (LPS)linterferon gamma (IFN-y) -induced NO production (LPS, 1 nglmL 10 μglmL; IFN-y, 101000 UlmL; incubation between 6 -48 hours; measured by Griess reagent). Results were compared with human blood monocytes (HBM) isolated from buffy coats. Inducible nitric oxide synthetase (iNOS) mRNA expression was looked for in PMΦ by reverse transcriptase polymerase chain reaction (RT-PCR). Furthermore, plasma (P) and peritoneal dialysate effluent (D) nitrite concentrations were measured in vivo.

The dialysate-to-plasma ratio (DIP) of nitrite concentration was inverse in the case of peritonitis compared to infection-free patients (peritonitis DIP = 1.3, non peritonitis DIP = 0.4; p < 0.01). PMΦ from peritonitis patients produced higher amounts of NO than did those from infection-free patients (0.040 ± 0.044 nmol per microgram cell protein versus 0.018 ± 0.015 nmol per microgram cell protein, p < 0.05). NO release could not be further enhanced by stimulation with LPS plus IFN-y (1 ng/mL, 250 UlmL, respectively). However, NO production in PMΦ from infection-free patients increased during in vitro stimulation (0.044 ± 0.031 nmol per microgram cell protein versus 0.018± 0.015 nmol per microgram cell protein, p < 0.01). An increase of iNOS mRNA expression could be demonstrated by RT-PCR. Blood monocytes from healthy donors also increased NO release during cytokine stimulation (0.032± 0.015 nmol per microgram cell protein versus 0.019 ± 0.009 nmol per microgram cell protein, p < 0.05).

Our results indicate that significant amounts of NO are released intraperitoneally in the case of bacterial peritonitis. PMΦ represent a site of NO production, though the absolute amounts released in vitro are only moderate. NO production can be induced in PMΦ and HBM by LPSIIFN-y stimulation in vitro.
Effects of Commercial Glucose-Based Peritoneal Dialysates on Peripheral Blood Phagocytes Apoptosis
Authors: Jin Hui Min , De Di Van , Xu Qin Jun
Published: February 2020

Background

Variable glucose-lactate-based peritoneal dialysates have negative effects on peritoneal macrophages and peripheral blood leukocytes, reducing the capacity of leukocytes for chemotaxis, bacterial killing. But few reports exist on cell apoptosis. To investigate the effects of glucose-lactate-based peritoneal dialysates on cultured phagocytes (monocytes and neutrophils), we focused on studying phagocyte apoptosis after brief exposure to commercial peritoneal dialysates.

Methods

Cell apoptosis is measured by flow cytometry (FCM) to detect phosphatidylserine (PS) exposure on early apoptotic cells using fluorescein-labeled annexin V. To mimic the composition of dialysate in vivo, where the freshly instilled solution mixes with the residual dialysate from the previous cycle, we performed the experiments using a mixture of fresh and spent dialysate (9:1). In our transient exposure experiments, monocytes and neutrophils were separately incubated in each of the test solutions (1.5% glucose an d 4.25% glucose dialysates) for 10 minutes or 30 minutes and afterward separated and resuspended in RPMI 1640 medium and cultured over the indicated time.

Results

After exposure to 1.5% glucose dialysates for 10 minutes, monocytes and neutrophils exhibited normally spontaneous apoptosis. After exposure to 4.25% glucose dialysate, monocytes underwent apoptosis increasingly, 21% % 5.0% versus 9.8% % 3.6% (p < 0.05) at 24 hours and 47% % 6.2% versus 16% % 4.0% (p < 0.01) at 72 hours compared with controls. For neutrophils, the results were discouraging: hypertonic dialysate not only increased apoptosis [65.36% % 2.6% versus 34.17% % 8.52% (p < 0.01) at 72 hours], but also induced cell necrosis. When incubation time was prolonged for 30 minutes, 1.5% dialysate acted like 4.25% dialysate, with the rate of apoptosis increasing rapidly [40% % 4.0% versus 16% % 4.0% (p < 0.01) at 72 hours for monocytes, and 66.90% % 5.6% versus 34.17% % 8.52% (p < 0.01) at 72 hours for neutrophils].

Conclusion

Glucose-lactate-based peritoneal dialysates can induce peripheral blood phagocyte apoptosis in vitro, which indicates that glucose plays an important role in triggering cell apoptosis. Therefore, looking for new, physiologic peritoneal dialysis fluids to replace conventional fluids is reasonable.
The 1997 Report of the Japanese National Registry Data on Pediatric Peritoneal Dialysis Patients
Authors: Hondaa Masataka
Published: February 2020

Objective

We have collected data on pediatric patients less than 16 years of age from the National Registry of Chronic Peritoneal Dialysis (PD). We present our experience with this population.

Design

The database details the patient numbers, age, outcome, cause of death, reason for terminating PD therapy, type of PD therapy, peritonitis, and catheter survival.

Patients

Of 807 patients, 70 patients (8.7%) were under 1 year of age, and 268 patients (33.2%) were under 6 years of age, clearly indicating that PD was the treatment of choice in young children. The duration on PD was 5 years or more in 200 patients (24.8%), which showed an increase in long-term PD patients from 11% in 1991. Patients on automated PD (APD) increased to 75% in 1997 from 9% in 1991.

Results

The outcomes for the total patient population of 807 as of the end of 1997 is: 253 patients (31.4%) were being successfully treated with PD, 87 patients (10.8%) died, 238 patients (29.5%) received a kidney transplant, and 121 (15.0%) were transferred to hemodialysis. The patient survival rate was 91% in 3 years and 86% in 5 years. The technique survival rate was 83% in 3 years and 71% in 5 years. The rate of peritonitis was 1 episode per 30 patient -months. The mean catheter duration was 2.25 years.

Conclusion

The patient and technique survival rates, the peritonitis rate, and the catheter survival improved recently. However, these data were worse in younger children (less than 6 years of age), indicating that extra-careful management is needed for this young age group.
Optimal Peritoneal Dialysis for Patients from Hong Kong
Authors: Lai Kar Neng , Lo Wai Kei
Published: February 2020

The socioeconomic statuses of Asian countries are diverse and government reimbursement policies for renal replacement programs vary greatly from one country to another. Both factors affect not only the availability of treatment but also the choice of dialysis modality. Despite the economic growth of Hong Kong over the past three decades, the resources spent by our government on health services are less than other developed countries. The National Health Service, which is run on a tight budget, supports almost 95% of the patients on renal replacement programs. Due to the cost-effectiveness and reimbursement from the government, 79% of patients with end-stage renal failure in Hong Kong are treated with continuous ambulatory peritoneal dialysis (CAPD). All new patients entering the renal replacement program run by the National Health Service are offered CAPD as the first-line dialytic treatment.

Due to budgetary constraint, over the past 10 years dialysis centers in Hong Kong have adopted a small-volume regime of 3 x 2-L daily exchanges as the initial dialysis prescription. This dialysis prescription will be considered to be suboptimal by Western standards, but the survival of these patients was comparable to, or even better than, other areas despite a lower Kt/V. These preliminary studies suggest small-volume dialysis may be an acceptable compromise in Asian populations with their smaller body size, given the financial constraints. These issues are especially important in Asia, where financial resources for renal replacement therapy are still limited in most countries and many patients have to continue working to pay for their renal replacement treatment. Using this small-volume dialytic regime, more patients may be treated with the limited financial resources. Furthermore, our experience raises the question of the importance of nutritional status in patient survival.
Utilization of 4-Factor Prothrombin Complex Concentrate for Reversal of Oral Factor Xa Inhibitor–Associated Acute Major Bleeding: A Case Series
Authors: Reynolds Tessa R. , Gilbert Brian W. , Hall Katherine M.
Published: February 2020

Objective:

In cases of oral factor Xa (FXa) inhibitor–associated acute major bleeding, several reversal strategies are available. Current guidelines recommend a dose of 50 U/kg if using 4-factor prothrombin complex concentrate (4F-PCC). A paucity of data exists with the use of 4F-PCC for FXa inhibitor reversal for acute major bleeding, specifically the most efficacious dosing regimens and safety data. The purpose of this case series is to describe the utilization of 4F-PCC for reversal of oral FXa inhibitor–associated acute major bleeding.

Methods:

This retrospective case series included all admitted patients 18 years and older who received 4F-PCC for oral FXa inhibitor–associated major bleeding. Major bleeding was defined using the International Society of Thrombosis and Hemostasis definition for major bleeding in nonsurgical patients. The primary outcome was achievement of hemostasis.

Results:

A total of 31 patients met inclusion criteria, with 17 receiving rivaroxaban and 14 receiving apixaban. Intracranial hemorrhage was the most common type of bleeding occurring in 15 (55%) patients. The median dose of 4F-PCC was 37 U/kg. Of the patients evaluated in the primary end point analysis, 68% achieved effective hemostasis. Four (12.9%) patients experienced a documented thrombotic event within 7 days of receiving 4F-PCC.

Conclusion:

The use of 4F-PCC for FXa inhibitor–associated acute major bleeding was effective for the majority of patients. The rate of thrombotic events appears higher compared to previously published studies, although major confounders exist and larger studies are needed to fully evaluate the safety of 4F-PCC for this indication.
Digital labour platforms and new forms of flexible work in developing countries: Algorithmic management of work and workers
Authors: Rani Uma , Furrer Marianne
Published: February 2020

Digital technologies have led to the emergence of new forms of flexible work, such as crowdwork or information and communication technology-enabled mobile work, over the past decade. This is considered as a positive development for its high flexibility in hours and place of work, and also for providing employment opportunities to workers in developing countries, individuals with disabilities or those with care responsibilities. This article examines the on-going trend in outsourcing low-skilled work to the crowd through online platforms, and how platform design features and algorithmic management are used by digital labour platforms to assign, monitor and evaluate work. The paper argues that these distinctive features of digital platforms have an impact on working conditions in terms of access to tasks, remuneration and working time flexibility. The paper draws on a global survey of 675 workers on five globally operating platforms in 27 developing countries. Its findings highlight the need for transparency in platform architecture, design and algorithms to ensure that workers are protected from the vulnerabilities they face with digital work.
Intraarticular Nodular Fasciitis of the Knee With MHY9-USP6 Fusion: A Case Report
Authors: Igrec Jasminka , Brčić Iva , Igrec Renato , Bergovec Marko , Kashofer Karl , Fuchsjäger Michael , Leithner Andreas , Liegl-Atzwanger Bernadette
Published: February 2020

Background. Nodular fasciitis (NF) is a self-limiting, benign mesenchymal neoplasm of fibroblastic/myofibroblastic origin. Due to the fast growth, cellularity, and frequently observed high mitotic count, it is commonly misdiagnosed as a sarcoma, often resulting in overtreatment. Intraarticular examples of NF are extremely rare. Radiologically, NF can mimic fibroma of the tendon sheath, tenosynovial giant cell tumor, and synovial chondromatosis. Histology can vary from hypercellular, mitotically active lesions to fibrotic, less cellular ones, and can, therefore, mimic other benign and low-grade malignant neoplasms. Recently, the MYH9-USP6 fusion has been found in up to 92% of NF. Case Presentation. In this article, we report a case of a 38-year-old patient with an intraarticular lesion, radiologically suspicious of tenosynovial giant cell tumor. Histology demonstrated a spindle cell lesion composed of fibroblasts/myofibroblasts embedded in a highly collagenous/hyalinized stroma, partly arranged in short fascicles. Extravasated erythrocytes and rare mitotic figures were present. Immunohistochemically, tumor cells expressed smooth muscle actin and were negative for desmin, β-catenin, CD34, and SOX10. These findings rendered the diagnosis of NF. Molecular analysis using next-generation sequencing (Archer FusionPlex Sarcoma Panel) revealed gene rearrangement involving USP6 and MYH9 supporting the diagnosis of NF in the knee joint. Conclusions. Radiological and histological features of NF can overlap with other benign and low-grade malignant lesion. Identification of the USP6 gene rearrangements or finding of the MYH9-USP6 fusion, especially in core needle biopsies and in the lesions occurring at unusual sites, can result in adequate therapeutic approach avoiding overtreatment.
von Willebrand Factor as a Predictor for Transplant-Associated Thrombotic Microangiopathy
Authors: Xu Zhenzhen , Luo Chengwei , Lai Peilong , Ling Wei , Wu Suijing , Huang Xin , Huang Lisi , Zhang Guanrong , Du Xin , Weng Jianyu
Published: February 2020

Transplant-associated thrombotic microangiopathy (TA-TMA) after hematopoietic stem cell transplantation (HSCT) is a severe complication associated with underlying endothelial damage. Secreted and released von Willebrand factor (vWF) correlates with endothelial cell injury, but its role in predicting prognosis for TA-TMA is unclear. In this prospective study, we evaluated the relationship between vWF and the incidence of TA-TMA after HSCT. A total of 79 consecutive patients undergoing HSCT from August 2016 to June 2018 were enrolled. Twenty-three (29%) patients met the established diagnostic criteria. Patients with TA-TMA had significantly higher nonrelapse mortality compared with those without TA-TMA (78.3% vs 8.9%; P < .001). Multivariable analysis demonstrated that vWF was a predictive biomarker for TA-TMA. The vWF value was higher for the TA-TMA group (mean ± standard deviation, 380.7% ± 78.8% vs 284.9% ± 104.5%; P < .001), and the area under the curve for vWF in the diagnosis of TA-TMA was 0.756. Furthermore, patients with ≥325% vWF had a higher 2-year cumulative hazard of TA-TMA (53.1% ± 8.2% vs 7.5% ± 4.2%; P < .001) and a lower 2-year survival (32.1% ± 9.1% vs 83.7% ± 6.2%; P < .001) compared with those with <325% vWF.

Conclusion:

von Willebrand factor is a useful predictor and prognostic measure for TA-TMA, which may help clinicians identify and manage this life-threatening disease earlier.
Comparison of single-input single-output and multi-input multi-output control strategies for performing sequential single-axis random vibration control test
Authors: D’Elia Giacomo , Mucchi Emiliano
Published: February 2020

This study investigates the use of single-input single-output and multi-input multi-output control strategies for performing single-axis vibration control tests. In particular, the work addresses the problem of high-level cross-axis responses during those tests. To compare the two control strategies, the study presents a test campaign carried out on an automotive component by exploiting two different test facilities: a single-axis shaker and a three-degree-of-freedom shaker table. The analysis points out the limitations of the single-input single-output control strategy. The coupling between the excitation system and the test specimen causes cross-axis excitations that compromise the test validity. In some cases, the cross-axis vibration level even exceeds the acceptable threshold of 14 dB. The multi-input multi-output control strategy instead, besides the feedback control of the main axis, allows the simultaneous vibration control along the two cross axes, thus, improving the quality of the single-axis test. Moreover, the work provides a detailed study followed by practical examples on how to better exploit the evident potential of the multi-input multi-output control strategy for definitely avoiding cross-axis vibration control problems.
Introduction to the Theme Issue on Dynamics of Health Behavior: Revisiting Systems Science for Population Health
Authors: Burke Jessica G. , Thompson Jessica R. , Mabry Patricia L. , Mair Christina F.
Published: February 2020

Systems science can help public health professionals to better understand the complex dynamics between factors affecting health behaviors and outcomes and to identify intervention opportunities. Despite their demonstrated utility in addressing health topics such influenza, tobacco control, and obesity, the associated methods continue to be underutilized by researchers and practitioners addressing health behaviors. This article discusses the growth of systems science methods (e.g., system dynamics, social network analysis, and agent-based modeling) in health research, provides a frame for the articles included in this themed issue, and closes with recommendations for enhancing the future of systems science and health behavior research. We argue that integrating systems sciences methods into health behavior research and practice is essential for improved population health and look forward to supporting the evolution of the field.
Diffusion/Contagion Processes on Social Networks
Authors: Valente Thomas W. , Vega Yon George G.
Published: February 2020

This study models how new ideas, practices, or diseases spread within and between communities, the diffusion of innovations or contagion. Several factors affect diffusion such as the characteristics of the initial adopters, the seeds; the structure of the network over which diffusion occurs; and the shape of the threshold distribution, which is the proportion of prior adopting peers needed for the focal individual to adopt. In this study, seven seeding conditions are modeled: (1) three opinion leadership indicators, (2) two bridging measures, (3) marginally positioned seeds, and (4) randomly selected seeds for comparison. Three network structures are modeled: (1) random, (2) small-world, and (3) scale-free. Four threshold distributions are modeled: (1) normal; (2) uniform; (3) beta 7,14; and (4) beta 1,2; all of which have a mean threshold of 33%, with different variances. The results show that seeding with nodes high on in-degree centrality and/or inverse constraint has faster and more widespread diffusion. Random networks had faster and higher prevalence of diffusion than scale-free ones, but not different from small-world ones. Compared with the normal threshold distribution, the uniform one had faster diffusion and the beta 7,14 distribution had slower diffusion. Most significantly, the threshold distribution standard deviation was associated with rate and prevalence such that higher threshold standard deviations accelerated diffusion and increased prevalence. These results underscore factors that health educators and public health advocates should consider when developing interventions or trying to understand the potential for behavior change.
Young Adult Women and Alcohol-Related Problems: The Key Role of Multidimensional Feminine Norms
Authors: Iwamoto Derek Kenji , Mui Vivian W.
Published: February 2020

Young adult college women are closing the gender gap with respect to heavy episodic drinking and alcohol-related problems. Accordingly, it is important to understand and examine the factors that help explain within-group differences in problematic drinking patterns among this vulnerable population. One promising theoretically-relevant factor that appears to explain problematic alcohol use among young adult women is conformity to multidimensional feminine norms. Feminine norms are the beliefs and/or expectations of what it means to be a woman. This review paper identifies the current trends and limitations of research examining the role of feminine norms on alcohol use among young adult women in college. The review of the literature suggests that relationship between feminine norms and alcohol problems is complex in that there are costs and benefits for endorsing and opposing different feminine norms. Women who endorse appearance and relational feminine norms such as striving to be thin, focusing on their appearance, and maintaining relationships are at heighten risk of engaging in heavy episodic drinking and alcohol problems. Women who endorse feminine norms including maintaining sexual relationships with one partner, endorse the belief that one should be modest, and sweet, and nice, and upholding domestic values are less likely to report alcohol problems. Clinical and future research recommendations are provided.
Liberalizing Bangladesh’s Services Trade: Is Joining Trade in Services Agreement the Way to Go?
Authors: Jansen Van Rensburg Susara J. , Rossouw Riaan , Viviers Wilma
Published: February 2020

Although currently limited, services trade holds great potential for Bangladesh, as services already make a major contribution to GDP and employment. Services represent an important alternative (in the longer term) or complement (in the shorter term) to ready-made garments (RMGs), which have long dominated Bangladesh’s export mix. The country is poised to see declining RMG export revenues when the country graduates out of least developed country (LDC) status and loses its trade preferences in global markets. To build domestic capacity with a view to developing its services export sector, Bangladesh needs to open its market to services imports. But what approach would be best? Can a plurilateral trade agreement (PTA) like the Trade in Services Agreement (TiSA), whose members have sought to stimulate their services sectors through more liberalized trade, ever be an option? We use a dynamic computable general equilibrium (CGE) model to simulate the effects of TiSA membership on Bangladesh’s economy. The results show that, overall, Bangladesh would derive marginal benefit from TiSA, but employment and exports would suffer. The worst-affected sectors would be agriculture and textiles and clothing, the country’s largest employers. To lessen the impact of increased foreign competition, a regional trade approach is recommended, supported by a sound national services strategy which would include a roadmap for tackling the country’s myriad supply-side shortcomings.

JEL: F13, F14, F15, F16
Impact of Remittances on Domestic Investment: A Panel Study of Six South Asian Countries
Authors: Dash Ranjan Kumar
Published: February 2020

Remittances inflow to South Asian countries increased significantly and is now one of the major sources of external finance overtaking traditional capital inflows such as foreign direct investment (FDI), foreign portfolio investment (FPI) and aid. However, the role of remittances in economic development has not been examined extensively, particularly for South Asian countries. This article examines the impact of remittances on domestic investment for South Asia over 1991–2017. Advanced panel estimation methods (unit root, cointegration and causality) are employed to account for potential country-specific heterogeneity and the endogeneity problem. Results of this study suggest that remittances increase domestic investment in the short term as well as in the long run for South Asia. This indicates that remittances are used not only for consumption purposes but also for investment activities such as human and physical capital development. The panel causality results suggest the presence of uni-directional causality running from remittances to domestic investment. Therefore, the result of this study supports the theoretical argument and previous empirical studies for other developing countries

JEL: C3, 01, F3, F22
The intimate public of relational welfare in Milan
Authors: Marchesi Milena
Published: February 2020

This paper examines the enactment of relational welfare in Milan through a focus on how new welfare professionals operating in deprived neighborhoods in Milan work to stimulate participation and relational energies among migrant and low-income parents. The paper introduces the notion of the “intimate public,” a spatial and relational milieu for activating an increasingly diverse public in the absence of traditional welfare resources. Through the lens of the intimate public, a number of effects come into view: First, the incitement to participate recasts the private as simultaneously a source of new forms of solidarity and a potential obstacle to social cohesion and integration. Second, assumptions about the organic and sustainable nature of citizen-based solidarity effectively erase the affective labor required to produce and sustain it, especially in marginalized neighborhoods. Finally, the intense relationality that characterizes the intimate public produces uncertainty and entanglements that bind professionals and participants in compelling ways.
Conditioning Electrical Stimulation Is Superior to Postoperative Electrical Stimulation in Enhanced Regeneration and Functional Recovery Following Nerve Graft Repair
Authors: Senger Jenna-Lynn B. , Chan Ashley W. M. , Chan K. Ming , Kwan-Wong Terence , Acton Leah , Olson Jaret , Webber Christine A.
Published: February 2020

Background. Autologous nerve graft is the most common clinical intervention for repairing a nerve gap. However, its regenerative capacity is decreased in part because, unlike a primary repair, the regenerating axons must traverse 2 repair sites. Means to promote nerve regeneration across a graft are needed. Postoperative electrical stimulation (PES) improves nerve growth by reducing staggered regeneration at the coaptation site whereas conditioning electrical stimulation (CES) accelerates axon extension. In this study, we directly compared these electrical stimulation paradigms in a model of nerve autograft repair. Methods. To lay the foundation for clinical translation, regeneration and reinnervation outcomes of CES and PES in a 5-mm nerve autograft model were compared. Sprague-Dawley rats were divided into: ( a) CES, ( b) PES, and ( c) no stimulation cohorts. CES was delivered 1 week prior to nerve cut/coaptation, and PES was delivered immediately following coaptation. Length of nerve regeneration (n = 6/cohort), and behavioral testing (n = 16/cohort) were performed at 14 days and 6 to 14 weeks post-coaptation, respectively. Results. CES treated axons extended 5.9 ± 0.2 mm, significantly longer than PES (3.8 ± 0.2 mm), or no stimulation (2.5 ± 0.2 mm) ( P < .01). Compared with PES animals, the CES animals had significantly improved sensory recovery (von Frey filament testing, intraepidermal nerve fiber reinnervation) ( P < .001) and motor reinnervation (horizontal ladder, gait analysis, nerve conduction studies, neuromuscular junction analysis) ( P < .01). Conclusion. CES resulted in faster regeneration through the nerve graft and improved sensorimotor recovery compared to all other cohorts. It is a promising treatment to improve outcomes in patients undergoing nerve autograft repair.
Cognitive Reserve as an Emerging Concept in Stroke Recovery
Authors: Rosenich Emily , Hordacre Brenton , Paquet Catherine , Koblar Simon A. , Hillier Susan L.
Published: February 2020

Stroke is a leading cause of death and disability. It is a complex and largely heterogeneous condition. Prognosis for variations in impairment and recovery following stroke continues to be challenging and inaccurate, highlighting the need to examine the influence of other currently unknown variables to better predict and understand interindividual differences in stroke impairment and recovery. The concept of “cognitive reserve,” a feature of brain function said to moderate the relationship between brain pathology and clinical outcomes, might provide a partial explanation. This review discusses the potential significance of cognitive reserve in the context of stroke, with reference to reduced burden of disability poststroke, health promotion, intervention and secondary prevention of cognitive impairment, ease and challenges of translation into clinical practice, prognosis and prediction of recovery, and clinical decisions and trial stratification. Discussions from the review aim to encourage stroke clinicians and researchers to better consider the role of premorbid, lifestyle-related variables, such as cognitive reserve, in facilitating successful neurological outcomes and recovery following stroke.
INFOMATAS multi-center systematic review and meta-analysis individual patient data of dynamic cerebral autoregulation in ischemic stroke
Authors: Beishon L , Minhas JS , Nogueira R , Castro P , Budgeon C , Aries M , Payne S , Robinson TG , Panerai RB
Published: February 2020

Rationale

Disturbances in dynamic cerebral autoregulation after ischemic stroke may have important implications for prognosis. Recent meta-analyses have been hampered by heterogeneity and small samples.

Aim and/or hypothesis

The aim of study is to undertake an individual patient data meta-analysis (IPD-MA) of dynamic cerebral autoregulation changes post-ischemic stroke and to determine a predictive model for outcome in ischemic stroke using information combined from dynamic cerebral autoregulation, clinical history, and neuroimaging.

Sample size estimates

To detect a change of 2% between categories in modified Rankin scale requires a sample size of ∼1500 patients with moderate to severe stroke, and a change of 1 in autoregulation index requires a sample size of 45 healthy individuals (powered at 80%, α = 0.05). Pooled estimates of mean and standard deviation derived from this study will be used to inform sample size calculations for adequately powered future dynamic cerebral autoregulation studies in ischemic stroke.

Methods and design

This is an IPD-MA as part of an international, multi-center collaboration (INFOMATAS) with three phases. Firstly, univariate analyses will be constructed for primary (modified Rankin scale) and secondary outcomes, with key co-variates and dynamic cerebral autoregulation parameters. Participants clustering from within studies will be accounted for with random effects. Secondly, dynamic cerebral autoregulation variables will be validated for diagnostic and prognostic accuracy in ischemic stroke using summary receiver operating characteristic curve analysis. Finally, the prognostic accuracy will be determined for four different models combining clinical history, neuroimaging, and dynamic cerebral autoregulation parameters.

Study outcome(s)

The outcomes for this study are to determine the relationship between clinical outcome, dynamic cerebral autoregulation changes, and baseline patient demographics, to determine the diagnostic and prognostic accuracy of dynamic cerebral autoregulation parameters, and to develop a prognostic model using dynamic cerebral autoregulation in ischemic stroke.

Discussion

This is the first international collaboration to use IPD-MA to determine prognostic models of dynamic cerebral autoregulation for patients with ischemic stroke.
The legal and jurisprudential evolution of the notion of employee
Authors: Perulli Adalberto
Published: February 2020

The essay analyses the concept of employed worker in the light of the expansive trend of labour law. Two perspectives are investigated. The first concerns the revisiting of the concept of employed worker through the interpretation of jurisprudence. Comparative analysis demonstrates a tendency, not univocal but prevalent, of jurisprudence to broaden the notion of subordinate work, which manifests itself through purposive interpretation techniques. The other perspective is that of the creation of intermediate categories, such as that of ‘worker’ in the UK or that of ‘parasubordinato’ work in Italy, or even the notion of ‘economically dependent self-employment’ (Spain, Germany), to which selectively apply some protections of subordinate work. The current challenge of labour law is therefore to be able to respond to changes in the production reality, exemplified by work through a digital platform, to provide adequate protection for new forms of work and new ways in which subordination is expressed.
Triglyceride concentrations and non-high-density lipoprotein cholesterol goal attainment in the ODYSSEY phase 3 trials with alirocumab
Authors: Vallejo-Vaz Antonio J , Leiter Lawrence A , Del Prato Stefano , Taskinen Marja-Riitta , Müller-Wieland Dirk , Bujas-Bobanovic Maja , Letierce Alexia , Mandel Jonas , Samuel Rita , Ray Kausik K
Published: February 2020

Aims

Guidelines recommend targeting non-high-density lipoprotein cholesterol to reduce cardiovascular risk. We assessed the impact of baseline triglycerides on non-high-density lipoprotein cholesterol goal attainment in 10 phase 3 trials with alirocumab versus control ( n = 4983).

Methods

Trials were grouped into four pools based on alirocumab dose (75–150 mg every 2 weeks), control (placebo/ezetimibe) and statin use. Baseline triglyceride quintiles were built within each pool. Non-high-density lipoprotein cholesterol goal attainment (very high risk: <100 mg/dl; moderate/high risk: <130 mg/dl), low-density lipoprotein cholesterol goal attainment (very high risk: <70 mg/dl; moderate/high risk: <100 mg/dl) and changes from baseline in lipid parameters were assessed at Week 24 among baseline triglyceride quintiles.

Results

Higher baseline triglycerides were associated with a worse cardiovascular risk profile. Low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol increased with higher triglycerides, but the magnitude in non-high-density lipoprotein cholesterol was three- to four-fold higher compared with the increase in low-density lipoprotein cholesterol. Non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol percentage reductions from baseline with alirocumab were similar regardless of baseline triglycerides. A greater proportion of alirocumab-treated patients attained non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol goals compared with placebo or ezetimibe. Unlike low-density lipoprotein cholesterol goal attainment, non-high-density lipoprotein cholesterol goal attainment significantly declined with increasing baseline triglycerides ( p < 0.05 for trend tests). A single standard deviation increase in baseline log(triglycerides) was significantly associated with lower odds ratios of attaining non-high-density lipoprotein cholesterol goals in the different pools and treatment (alirocumab/placebo/ezetimibe) groups, unlike low-density lipoprotein cholesterol goal attainment.

Conclusion

Individuals with increased triglycerides have higher non-high-density lipoprotein cholesterol levels and lower rates of non-high-density lipoprotein cholesterol goal attainment (unlike low-density lipoprotein cholesterol goal attainment). Alirocumab improves non-high-density lipoprotein cholesterol goal attainment in this population. These results highlight the impact of triglycerides on non-high-density lipoprotein cholesterol and the need for novel therapies targeting triglyceride-related pathways.
A scoring system for predicting individual treatment effects of statins in type 2 diabetes patients on haemodialysis
Authors: Genser Bernd , Wanner Christoph , März Winfried
Published: February 2020

Aims

Haemodialysis patients have high cardiovascular disease risk. Although statins reduce this risk in chronic kidney disease, randomised trials in haemodialysis patients show no benefit. Post-hoc analyses of the German Diabetes Dialysis (4D) study identified patient-specific markers associated with heterogeneous treatment effects. We combined these markers to develop a score for predicting individual effects of statins in these patients.

Methods and results

We used data from the 4D study, enrolling 1255 haemodialysis patients with type 2 diabetes mellitus, randomised to atorvastatin or placebo and followed for a composite cardiovascular endpoint. We calculated two scores: score 1 based on all 23 predictive markers and score 2 based on 17 clinically accessible markers. Groups stratified by score 1 showed differential treatment effects: for score <26 (458 patients; 36%), the hazard ratio (95% confidence interval) was 1.54 (1.16–2.03), suggesting harm; for 26–31 (331 patients; 26%), it was 1.03 (0.72–1.48), suggesting a neutral effect; and for >31 (466 patients; 38%), it was 0.43 (0.30–0.60), suggesting a benefit. Statins also significantly reduced all-cause mortality in the benefit group. Stratification by score 2 yielded similar results but a smaller group gaining benefit (360 patients).

Conclusion

Statin effects in haemodialysis patients can be predicted by markers associated with plausible relevant mechanisms including cholesterol metabolism, atherosclerosis, protein energy wasting, or competing risks. In clinical practice, the score could aid in risk stratification, not only to select patients who benefit from statins but also to identify those whom treatment could harm.
Interpersonal Strategies in E-Complaint Refusals: Textbook Advice Versus Actual Situated Practice
Authors: Decock Sofie , De Clerck Bernard , Van Herck Rebecca
Published: February 2020

This article reports on the representation and operationalization of interpersonal attention in complaint management by comparing business textbooks, service recovery research, and situated practice. While textbooks commonly recommend the use of interpersonal strategies when writing complaint refusals, service recovery research points toward contextual differences in this regard. We use an authentic sample of complaint refusals from an intercultural business-to-business setting to show that the decontextualized recommendations in textbooks are not always applied in actual practice and that this lack of interpersonal attention need not be problematic.
Combination of dasatinib with chemotherapy in previously untreated core binding factor acute myeloid leukemia: CALGB 10801
Authors: Marcucci Guido , Geyer Susan , Laumann Kristina , Zhao Weiqiang , Bucci Donna , Uy Geoffrey L. , Blum William , Eisfeld Ann-Kathrin , Pardee Timothy S. , Wang Eunice S. , Stock Wendy , Kolitz Jonathan E. , Kohlschmidt Jessica , Mrózek Krzysztof , Bloomfield Clara D. , Stone Richard M. , Larson Richard A.
Published: February 2020

Acute myeloid leukemia (AML) with either t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22) is referred to as core binding factor (CBF) AML. Although categorized as favorable risk, long-term survival for these patients is only ∼50% to 60%. Mutated (mut) or overexpressed KIT, a gene encoding a receptor tyrosine kinase, has been found almost exclusively in CBF AML and may increase the risk of disease relapse. We tested the safety and clinical activity of dasatinib, a multi-kinase inhibitor, in combination with chemotherapy. Sixty-one adult patients with AML and CBF fusion transcripts (RUNX1/RUNX1T1 or CBFB/MYH11) were enrolled on Cancer and Leukemia Group B (CALGB) 10801. Patients received cytarabine/daunorubicin induction on days 1 to 7 and oral dasatinib 100 mg/d on days 8 to 21. Upon achieving complete remission, patients received consolidation with high-dose cytarabine followed by dasatinib 100 mg/d on days 6 to 26 for 4 courses, followed by dasatinib 100 mg/d for 12 months. Fifteen (25%) patients were older (aged ≥60 years); 67% were CBFB/MYH11–positive, and 19% harbored KITmut. There were no unexpected or dose-limiting toxicities. Fifty-five (90%) patients achieved complete remission. With a median follow-up of 45 months, only 16% have relapsed. The 3-year disease-free survival and overall survival rates were 75% and 77% (79% and 85% for younger patients [aged <60 years], and 60% and 51% for older patients). Patients with KITmut had comparable outcome to those with wild-type KIT (3-year rates: disease-free survival, 67% vs 75%; overall survival, 73% vs 76%), thereby raising the question of whether dasatinib may overcome the negative impact of these genetic lesions. CALGB 10801 was registered at www.clinicaltrials.gov as #NCT01238211.
KIR B donors improve the outcome for AML patients given reduced intensity conditioning and unrelated donor transplantation
Authors: Weisdorf Daniel , Cooley Sarah , Wang Tao , Trachtenberg Elizabeth , Vierra-Green Cynthia , Spellman Stephen , Sees Jennifer A. , Spahn Ashley , Vogel Jenny , Fehniger Todd A. , Woolfrey Ann E. , Devine Steven M. , Ross Maureen , Waller Edmund K. , Sobecks Ronald M. , McGuirk Joseph , Oran Betul , Farag Sherif S. , Shore Tsiporah , Van Besien Koen , Marsh Steven G. E. , Guethlein Lisbeth A. , Parham Peter , Miller Jeffrey S.
Published: February 2020

Natural killer (NK) cell recognition and killing of target cells are enhanced when inhibitory killer immunoglobulin-like receptors (KIR) are unable to engage their cognate HLA class I ligands. The genes of the KIR locus are organized into either KIR B haplotypes, containing 1 or more activating KIR genes or KIR A haplotypes, which lack those genes. Analysis of unrelated donor (URD) hematopoietic cell transplants (HCT), given to acute myeloid leukemia (AML) patients between 1988 and 2009, showed that KIR B haplotype donors were associated with better outcomes, primarily from relapse protection. Most of these transplants involved marrow grafts, fully myeloablative (MAC) preparative regimens, and significant HLA mismatch. Because the practice of HCT continues to evolve, with increasing use of reduced intensity conditioning (RIC), peripheral blood stem cell grafts, and better HLA match, we evaluated the impact of URD KIR genotype on HCT outcome for AML in the modern era (2010-2016). This analysis combined data from a prospective trial testing URD selection based on KIR genotypes (n = 243) with that from a larger contemporaneous cohort of transplants (n = 2419). We found that KIR B haplotype donors conferred a significantly reduced risk of leukemia relapse and improved disease-free survival after RIC, but not MAC HCT. All genes defining KIR B haplotypes were associated with relapse protection, which was significant only in transplant recipients expressing the C1 epitope of HLA-C. In the context of current HCT practice using RIC, selection of KIR B donors could reduce relapse and improve overall outcome for AML patients receiving an allogeneic HCT.
High-risk LCH in infants is serially transplantable in a xenograft model but responds durably to targeted therapy
Authors: Lee Lynn H. , Krupski Christa , Clark Jason , Wunderlich Mark , Lorsbach Robert B. , Grimley Michael S. , Burwinkel Matthew , Nelson Adam , Kumar Ashish R.
Published: February 2020

Langerhans cell histiocytosis (LCH) is a rare hematologic neoplasm characterized by a clonal proliferation of Langerhans-like cells. Genomic profiling has identified recurrent somatic activating mutations in the mitogen-activated protein kinase pathway, which are targetable by small-molecule inhibitors. However, key questions such as the curative potential of targeted therapy and the cell of origin remain unanswered. In this study, we describe clinical outcomes of a series of pediatric patients with multisystem BRAF V600E–mutant LCH, as well as the results of accompanying murine xenograft experiments. Four infants with LCH (range, 7-11 months at diagnosis) and secondary hemophagocytic lymphohistiocytosis were referred to our institution and subsequently treated with the BRAF V600E–specific inhibitor dabrafenib. All patients achieved complete clinical responses by 8 weeks of therapy, with remissions lasting a median of 36 months (range, 27-42 months). One infant successfully discontinued therapy long-term upon achieving a molecular response by real-time quantitative polymerase chain reaction (RT-qPCR). We further characterized the disease-propagating cell population in a subset of these patients by transplanting whole bone marrow into immunodeficient mice. Xenografted animals exhibited decreased survival with hematologic abnormalities, splenomegaly, and histiocytic infiltrates in the bone marrow resembling human disease. This process could also be secondarily transplanted, resulting in a comparable disease latency with similar histologic findings. These data further support the presence of a disease-initiating cell in the bone marrow compartment. We demonstrate that despite aggressive disease behavior in a xenograft model, these patients can achieve sustained clinical remissions with targeted monotherapy, with a select subset achieving molecular responses by RT-qPCR.