bluuebunny/crossref_metadata_2025 huggingface dataset:
Constructions of modern Czech masculinity and feminity in memoirs written at the turn of the 19th century (1870–1918)
Authors: Filipowicz Marcin , Zachová Alena
Published: March 2016

This article explores the ways the masculinity and feminity of the emerging Czech elite were constructed at the turn of the 19th century. Using an often neglected literary genre of the memoirs, the study draws on extensive excerpts from memoir related to the town of Hradec Králové (Königgrätz), situated in Bohemia’s part of the Austro-Hungarian monarchy at that time. Embodied in the new constructions of masculinity and feminity, the nation-building process was particularly vivid here. The article shows that the education of the young Czech elite was shaped by a particular ‘masculine schizophrenia’ and that their new modern masculinity was constructed in relation to their Austrian counterparts. In analyzing the identity constructions of women, the article identifies discrepancies found between the highly approved women’s emancipatory process in Czech society and the traditional gender order which allocated women to the household. Particularly, the study contributes to a revival of the memoir as an important history source, containing extremely valuable and highly nuanced insights into the formation of a new gender order which are not available in official narratives.
The frontiers of participatory public engagement
Authors: Mahony Nick , Stephansen Hilde C
Published: March 2016

Currently missing from critical literature on public engagement with academic research is a public-centric analysis of the wider contemporary context of developments in the field of public engagement and participation. Drawing on three differently useful strands of the existing theoretical literature on the public, this article compares a diverse sample of 100 participatory public engagement initiatives in order to first, analyse a selection of the myriad ways that the public is being constituted and supported across this contemporary field and second, identify what socio-cultural researchers might learn from these developments. Emerging from this research is a preliminary map of the field of public engagement and participation. This map highlights relationships and divergences that exist among diverse forms of practice and brings into clearer view a set of tensions between different contemporary approaches to public engagement and participation. Two ‘frontiers’ of participatory public engagement that socio-cultural researchers should attend are also identified. At the first, scholars need to be critical regarding the particular versions of the public that their preferred approach to engagement and participation supports and concerning how their specific identifications with the public relate to those being addressed across the wider field. At the second frontier, researchers need to consider the possibilities for political intervention that public engagement and participation practice could open out, both in the settings they are already working and also in the much broader, rapidly developing and increasingly complicated contemporary field of public engagement and participation that this article explores.
Element stiffness index distribution method for multi-crack detection of a beam-like structure
Authors: Nguyen Khoa Viet , Van Nguyen Quang
Published: March 2016

In this article, a method using “element stiffness index distribution” for multi-crack detection of a beam-like structure is presented. The element stiffness index distribution is defined as a vector of norms of sub-matrices corresponding to element stiffness matrices calculated from the reconstructed global stiffness matrix of the beam. When there is a crack at an element, the element stiffness index of that element will be changed. Therefore, by monitoring the change in the element stiffness index distribution, the crack can be detected. A significant peak in the element stiffness index distribution is the indicator of the crack existence. The crack location and the crack depth can be determined from the location of the peak and the height of the peak. In this study, the global stiffness matrix is reconstructed from the measured frequency response functions instead of mode shapes to avoid some limitations of the mode shape-based methods for crack detection. Numerical simulation results for the cases of single crack and double cracks are provided. The results showed that cracks with a depth as small as 10% of the beam height can be detected by the method. The proposed method can be applied with the noise level up to 10%.
The indoor thermal environment of rural school classrooms in Northwestern China
Authors: Liu Yanfeng , Jiang Jing , Wang Dengjia , Liu Jiaping
Published: March 2016

School classroom thermal environments could impact on thermal comfort and learning performance. Currently, the majority of research on the school indoor thermal environment has been focusing on urban areas, but notably little research has been conducted on rural schools. A field study was undertaken during the winter in Northwestern China, in order to investigate the indoor thermal environment and the impact on students’ thermal comfort and learning performance in rural primary and secondary schools. Through subjective surveys and objective measurements, we gathered 763 sets of data and questionnaires. Together with the measured air temperature, relative humidity, air velocity, globe temperature, teenagers’ activity levels and clothing insulation levels, the sensations of the indoor air conditions and the learning performance were evaluated. The current thermal environment situation in rural schools was identified. The neutral temperature was found to be approximately 15.0℃ with an average clothing insulation of 1.6 clo. Overall, the environment is satisfactory and comfortable. Moreover, the results from the students’ fatigue testing demonstrated the temperature corresponding to the highest learning performance is lower than the actual neutral temperature by about 1.0℃. The basic parameters of our findings have provided a future reference for improvement of the thermal environment in rural schools.
Development of a memory center for older adults in Almaty, Kazakhstan: Innovative Practice
Authors: Thomas David W , Yeshmanova Ainur , Akanova Assiya , Umutbayeva Gulmira , Abikulova Akmaral , Chaikovska Vera
Published: March 2016

Recognizing the economic and health-outcome value of early cognitive assessment and intervention among its older citizens has guided the Innovative Research School in Gerontology of the SD Asfendiyarov Kazakh National Medical University to begin the process of establishing its nation’s first memory center in Almaty, Kazakhstan. Life expectancy in Kazakhstan, which continues to undergo health-care reform since its independence in 1991 from the former Soviet Union, has steadily risen from 64.4 years in 1996 to 68.67 in 2009. With increased life expectancy has been a corresponding rise in cognitive impairments among older adults. The components of the Memory Center, which comprises assessment, education and support, non-pharmaceutical and pharmaceutical interventions, are described.
“It was then that I thought ‘whaat? This is not my Dad”: The implications of the ‘still the same person’ narrative for children and young people who have a parent with dementia
Authors: Sikes Pat , Hall Mel
Published: March 2016

This research used auto/biographical interviews to explore the experiences of 19, 8 to 31 year olds who had a parent with dementia. Thematic analysis revealed challenges occasioned by the master narrative that people with dementia are ‘still’ the same person they were prior to the onset of their condition. While this notion is – rightly – at the heart of person-centered care in dementia services, the ‘still’ discourse conflicts with the experiences of young people. Their accounts suggest that the construction of their parent as the same person is not helpful and that, furthermore, expectations that they will behave and feel towards that parent as they did before are a source of distress in what is already a challenging situation. This paper highlights the need to equip young people with support that acknowledges that their parent may well be drastically different to the Mum or Dad they previously ‘knew’.
Fire and thermal resistance properties of chemically treated ligno-cellulosic coconut fabric–reinforced polymer eco-nanocomposites
Authors: Rajini N , Winowlin Jappes JT , Siva I , Varada Rajulu A , Rajakarunakaran S
Published: March 2016

The present work was aimed to develop naturally woven coconut sheath/polyester biocomposites. In these composites, montmorillonite nanoclay (5 wt%) was used as a second filler. The heat releasing rate and other flammability properties were studied using cone calorimeter. The coconut sheath reinforcement in polyester matrix significantly decreased the heat releasing rate when compared to that of the pristine polyester. However, the time to ignite the composite material was shorter than that of the pure polyester. The morphological changes on the fiber surface by the chemical modification significantly influenced the heat-releasing rate and other flammability characteristics due to better interfacial bonding. The hybridization effect of 5 wt% of nanoclay could greatly decrease the heat release rate and the mass loss rate of the composites by char formation mechanism. The characterization techniques such as the scanning electron microscopy and the transmission electron microscopy were used to study the morphological state of the fiber surface and dispersion of clay in the polyester nanocomposites. The thermogravimetric analysis was also carried out to study the effect of the nanoclay on the thermal stability of the coconut sheath/polyester composites at higher temperatures.
Experiences and Learning Needs of African American Family Dementia Caregivers
Authors: Samson Zoe Blake , Parker Monica , Dye Clinton , Hepburn Kenneth
Published: March 2016

Dementia family caregivers display significant rates of psychological and physical symptoms. African Americans (AAs) are disproportionately affected by dementia. African American caregivers display unique patterns of symptomology and responses to interventions designed to promote caregiver well-being. This study analyzed qualitative focus group data from 32 AA caregivers to explore how issues of race and culture may be incorporated into a culturally sensitive intervention for AA dementia family caregivers. Caregivers were asked scripted questions about their caregiving experiences and to suggest alterations to an existing psychoeducation program. Analysis revealed 4 key themes: the tradition of family care, caregiving and caregiving issues, culturally appropriate care, and navigating without a map. Suggestions for an educational program included a focus on developing caregiver skills and knowledge for caregiving, promotion of self-care, and reflection on the AA family and community as resources for care.
Spiritual Care Education and Rural Systems in Swan River
Authors: Curry Janel , McCallum Margaret , Rodriguez V Jorge Juan
Published: March 2016

The provision of spiritual care, and the training of spiritual care providers, must be embedded within the larger systems (economic, social, generational, and environmental) and communities within which clients reside. This study analyzes the results of a systems approach to CPE training that focused on the rural context of Swan River, Manitoba. It addresses the need for new approaches to contextualizing CPE training and for understanding the uniqueness of rural contexts in particular.
The Haircut
Authors: Baroody Joseph
Published: March 2016

The article describes my experience – and the lessons learned – with a terminally ill patient in 1977 as a clinical pastoral education chaplain intern.
‘Paramedical’ Healing in Hospitals: The Expansion of Spiritual Care in Seoul
Authors: Park Irene Yung
Published: March 2016

Emotional and spiritual healing stand at the center of the activity of Catholic pastoral caregivers attending to the sick in non-Catholic hospitals in Seoul. In this paper I explore how these agents understand their practice as part of a holistic human healing, positioning their work side by side with medical healing. I also examine how their role is both confirmed and challenged against the backdrop of the growing commercialization of the health care industry under the neoliberal paradigm.
Adherence adjustment in the Coronary Drug Project: A call for better per-protocol effect estimates in randomized trials
Authors: Murray Eleanor J , Hernán Miguel A
Published: March 2016

Background:

In many randomized controlled trials, patients and doctors are more interested in the per-protocol effect than in the intention-to-treat effect. However, valid estimation of the per-protocol effect generally requires adjustment for prognostic factors associated with adherence. These adherence adjustments have been strongly questioned in the clinical trials community, especially after 1980 when the Coronary Drug Project team found that adherers to placebo had lower 5-year mortality than non-adherers to placebo.

Methods:

We replicated the original Coronary Drug Project findings from 1980 and re-analyzed the Coronary Drug Project data using technical and conceptual developments that have become established since 1980. Specifically, we used logistic models for binary outcomes, decoupled the definition of adherence from loss to follow-up, and adjusted for pre-randomization covariates via standardization and for post-randomization covariates via inverse probability weighting.

Results:

The original Coronary Drug Project analysis reported a difference in 5-year mortality between adherers and non-adherers in the placebo arm of 9.4 percentage points. Using modern approaches, we found that this difference was reduced to 2.5 (95% confidence interval: −2.1 to 7.0).

Conclusion:

Valid estimation of per-protocol effects may be possible in randomized clinical trials when analysts use appropriate methods to adjust for post-randomization variables.
Some reliability indexes and sojourn time distributions for a repairable degradation model
Authors: Du Shijia , Cui Lirong , Lin Cong
Published: March 2016

In this article, a degradation model for repairable systems is developed, based on a continuous-time Markov process with multiple discrete states. The discrete states are divided into two types: up and down states, and represent that the system is undergoing a range of degradation levels from perfect functioning to complete failure. The closed-form expressions of four common reliability indexes are derived using the technique of aggregated stochastic process. The indexes include point availability, multi-point availability, interval availability and multi-interval availability. Also, the analytical solution to lower degradation probabilities and some sojourn time distributions are derived using the technique of aggregated stochastic process. Finally, numerical examples are given to illustrate the results obtained in the article.
Casino Customers’ Intention to Join a Loyalty Rewards Program
Authors: Quigno Justin , Zhang Lu
Published: March 2016

Companies have long sought to use a loyalty rewards program as a way to maintain loyal customers, encourage purchasing, and attract new customers by providing certain incentives. Despite the fruitful research on the impact of such programs on customers’ purchasing behavior and loyalty, there is limited research on factors influencing customers’ likelihood to join a program in the casino industry. To bridge the gap, the present research aims to examine the combined effect of number of tiers and gender on customers’ attitudes and intention to join a loyalty rewards program. The results indicate that male customers exhibited more positive attitudes and higher level of intention to join a program that has four tiers (vs. two tiers). Conversely, female customers’ attitudes and joining intentions are stronger when facing a loyalty rewards program containing two tiers (vs. four tiers). The underlying psychological mechanism is individuals’ need for status (NFS).
Glue septal ablation: A promising alternative to alcohol septal ablation
Authors: Okutucu Sercan , Aytemir Kudret , Oto Ali
Published: March 2016

Hypertrophic cardiomyopathy (HCM) is defined as myocardial hypertrophy in the absence of another cardiac or systemic disease capable of producing the magnitude of present hypertrophy. In about 70% of patients with HCM, there is left ventricular outflow tract (LVOT) obstruction (LVOTO) and this is known as obstructive type of hypertrophic cardiomyopathy (HOCM). Cases refractory to medical treatment have had two options either surgical septal myectomy or alcohol septal ablation (ASA) to alleviate LVOT gradient. ASA may cause some life-threatening complications including conduction disturbances and complete heart block, hemodynamic compromise, ventricular arrhythmias, distant and massive myocardial necrosis. Glue septal ablation (GSA) is a promising technique for the treatment of HOCM. Glue seems to be superior to alcohol due to some intrinsic advantageous properties of glue such as immediate polymerization which prevents the leak into the left anterior descending coronary artery and it is particularly useful in patients with collaterals to the right coronary artery in whom alcohol ablation is contraindicated. In our experience, GSA is effective and also a safe technique without significant complications. GSA decreases LVOT gradient immediately after the procedure and this reduction persists during 12 months of follow-up. It improves New York Heart Association functional capacity and decrease interventricular septal wall thickness. Further studies are needed in order to assess the long-term efficacy and safety of this technique.
Postoperative Abdominal NIRS Values Predict Low Cardiac Output Syndrome in Neonates
Authors: Hickok Rhiannon L. , Spaeder Michael C. , Berger John T. , Schuette Jennifer J. , Klugman Darren
Published: March 2016

Background:

The development of low cardiac output syndrome (LCOS) after cardiopulmonary bypass (CPB) occurs in up to 25% of neonates and is associated with increased morbidity. Invasive cardiac output monitors such as pulmonary artery catheters have limited availability and are costly. Near-infrared spectroscopy (NIRS) is a noninvasive tool for monitoring regional oxygenation in neonates in the cardiac intensive care unit (CICU). We hypothesize that anterior abdominal NIRS may aid in the early identification of LCOS after cardiac surgery.

Methods:

Prospective observational study from October 2013 to October 2014 of all neonates with congenital heart disease admitted to the CICU following CPB. Abdominal NIRS values were continuously recorded upon CICU admission and for the subsequent 24-hour period. The primary outcome was the development of LCOS. Low cardiac output syndrome was defined as the presence of metabolic lactic acidosis (pH < 7.3 and lactate > 4) or addition of a new vasoactive agent or a vasoactive inotropic score > 15. Autoregressive time series models were constructed for each patient based on the continuously recorded NIRS values, and patients were stratified by development of LCOS.

Results:

Twenty-seven neonates met inclusion criteria, of whom 11 developed LCOS. Neonates who developed LCOS had lower constant NIRS values (49% vs 66%, P < .001). Constant NIRS values less than 58% best predicted development of LCOS with a sensitivity of 100% and specificity of 69%.

Conclusion:

Lower constant anterior abdominal NIRS values in the early postoperative period may allow early identification of neonates at risk for LCOS.
The Kidney in Critical Cardiac Disease
Authors: Cooper David S. , Basu Rajit K. , Price Jack F. , Goldstein Stuart L. , Krawczeski Catherine D.
Published: March 2016

The field of cardiac intensive care continues to advance in tandem with congenital heart surgery. The focus of intensive care unit care has now shifted to that of morbidity reduction and eventual elimination. Acute kidney injury (AKI) after cardiac surgery is associated with adverse outcomes, including prolonged intensive care and hospital stays, diminished quality of life, and increased long-term mortality. Acute kidney injury occurs frequently, complicating the care of both postoperative patients and those with heart failure. Patients who become fluid overloaded and/or require dialysis are at high risk of mortality, but even minor degrees of AKI portend a significant increase in mortality and morbidity. Clinicians continue to seek methods of early diagnosis and risk stratification of AKI to prevent its adverse sequelae. Previous conventional wisdom that survivors of AKI fully recover renal function without subsequent consequences may be flawed.
Advancing Cardiac Critical Care
Authors: McBride Mary E. , Floh Alejandro , Krishnamurthy Ganga , Checchia Paul , Klugman Darren
Published: March 2016

The evolution and development of pediatric cardiac critical care as a distinct subspecialty have occurred rapidly over the past 20 years. As the field has grown, models for education, training, and care delivery have changed as well. This review will highlight the current state of education, training, and parental involvement in care delivery for pediatric cardiac critical care as initially
Diaphragmatic Fenestration for Resistant Pleural Effusions After Univentricular Palliation
Authors: Talwar Sachin , Das Anupam , Choudhary Shiv Kumar , Airan Balram
Published: March 2016

Objective:

Persistent pleural effusions are a major source of morbidity after univentricular repair. These are often refractory to conventional conservative therapy. We adopted a strategy of diaphragmatic fenestration (DF) in such patients and report the results.

Methods:

Between January 2002 and 2014, we performed DF in 12 patients using an original technique that was first described by us. The medical records of all these patients were studied. Preoperative characteristics, amount and duration of effusions, and time to removal of chest tubes following DF were studied.

Results:

Mean age was 101 ± 57.9 months (range: 38-180 months), and mean body weight was 18.8 ± 5.8 kg (range: 11-28 kg). Five had a bidirectional Glenn, four had lateral tunnel Fontan, and three had an extracardiac Fontan as initial procedure. The average pleural drainage prior to DF was 352.5 ± 152 mL/24 h (18.75 mL/kg/24 h) for a median period of 33 days (bidirectional Glenn 216 ± 85 mL/24 h [16.5 mL/kg/24 h] for 30 days and total cavopulmonary connection 450 ± 104 mL/24 h [22.5 mL/kg/24 h] for 36 days). All patients underwent DF. Additionally, five patients underwent thoracic duct ligation on the left side. Postoperative chest drainage after DF was 25 mL/d for a median of 4 days, and the chest tubes could be removed in a median of 5.5 days (mean 7 days). There were no complications related to DF.

Conclusions:

In patients with persistent pleural effusions following univentricular palliation, DF is an attractive option when conventional therapies have failed. This original technique of DF is simple, reproducible, cost-effective, and free of any known complications.
Pneumococcal Sepsis Complicated by Splenic Abscesses and Purpura Fulminans in a 15-Month-Old Child
Authors: Pangonis Scott , Patamasucon Pisespong , Fitzpatrick Ellen
Published: March 2016

Streptococcus pneumoniae is an invasive organism that causes a wide range of common diseases, including sinusitis, acute otitis media, and pneumonia. Splenic abscesses and purpura fulminans (PF) are rare complications of pneumococcal disease. Splenic abscesses caused by S pneumoniae have only been reported in the adult literature. PF has been described in the pediatric population as a rare complication in patients with invasive pneumococcal disease (IPD) with and without underlying immunological disorders such as asplenia. Here, we report a patient with IPD complicated by splenic abscesses and PF. Our patient initially presented with bacteremia, septic shock, and disseminated intravascular coagulation. She subsequently developed PF and splenic abscesses. She survived her illness after receiving a total of 8 weeks of antibiotic therapy. This case highlights 2 rare complications of IPD and demonstrates the need to keep pneumococcal disease in the differential diagnosis even in children whose vaccination status is up to date.
Characteristics and risk factors for 28-day mortality of hospital acquired fungemias in ICUs: data from the EUROBACT study
Authors: Paiva José-Artur , Pereira José Manuel , Tabah Alexis , Mikstacki Adam , de Carvalho Frederico Bruzzi , Koulenti Despoina , Ruckly Stéphane , Çakar Nahit , Misset Benoit , Dimopoulos George , Antonelli Massimo , Rello Jordi , Ma Xiaochun , Tamowicz Barbara , Timsit Jean-François
Published: March 2016

Background

To characterize and identify prognostic factors for 28-day mortality among patients with hospital-acquired fungemia (HAF) in the Intensive Care Unit (ICU).

Methods

A sub-analysis of a prospective, multicenter non-representative cohort study conducted in 162 ICUs in 24 countries.

Results

Of the 1156 patients with hospital-acquired bloodstream infections (HA-BSI) included in the EUROBACT study, 96 patients had a HAF. Median time to its diagnosis was 20 days (IQR 10.5–30.5) and 9 days (IQR 3–15.5) after hospital and ICU admission, respectively. Median time to positivity of blood culture was longer in fungemia than in bacteremia (48.7 h vs. 38.1 h; p = 0.0004). Candida albicans was the most frequent fungus isolated (57.1 %), followed by Candida glabrata (15.3 %) and Candida parapsilosis (10.2 %). No clear source of HAF was detected in 33.3 % of the episodes and it was catheter-related in 21.9 % of them. Compared to patients with bacteremia, HAF patients had a higher rate of septic shock (39.6 % vs. 21.6 %; p = 0.0003) and renal dysfunction (25 % vs. 12.4 %; p = 0.0023) on admission and a higher rate of renal failure (26 % vs. 16.2 %; p = 0.0273) at diagnosis. Adequate treatment started within 24 h after blood culture collection was less frequent in HAF patients (22.9 % vs. 55.3 %; p < 0.001). The 28-day all cause fatality was 40.6 %. According to multivariate analysis, only liver failure (OR 14.35; 95 % CI 1.17–175.6; p = 0.037), need for mechanical ventilation (OR 8.86; 95 % CI 1.2–65.24; p = 0.032) and ICU admission for medical reason (OR 3.87; 95 % CI 1.25–11.99; p = 0.020) were independent predictors of 28-day mortality in HAF patients.

Conclusions

Fungi are an important cause of hospital-acquired BSI in the ICU. Patients with HAF present more frequently with septic shock and renal dysfunction on ICU admission and have a higher rate of renal failure at diagnosis. HAF are associated with a significant 28-day mortality rate (40 %), but delayed adequate antifungal therapy was not an independent risk factor for death. Liver failure, need for mechanical ventilation and ICU admission for medical reason were the only independent predictors of 28-day mortality.
Anaemia is not a risk factor for progression of acute kidney injury: a retrospective analysis
Authors: Powell-Tuck Jonah , Crichton Siobhan , Raimundo Mario , Camporota Luigi , Wyncoll Duncan , Ostermann Marlies
Published: March 2016

Background

In hospitalised patients, anaemia increases the risk of developing acute kidney injury (AKI). Our aim was to determine whether anaemia also has an impact on the risk of progression from early AKI to more severe AKI in critically ill patients.

Methods

We retrospectively analysed the data of patients admitted to the adult intensive care unit between 2007 and 2009 who had AKI I as per the AKI Network classification, and who had undergone haemodynamic monitoring within 12 h of AKI I. We collected baseline characteristics, severity of illness, haemoglobin (Hb), and haemodynamic parameters in the first 12 h of AKI I and differentiated between patients who progressed to AKI III and those who did not. Univariate and multivariate logistic regression analyses were used to identify risk factors for progression. Associations between Hb, arterial oxygen saturation and cardiac index were explored by receiver operating characteristic curve analysis.

Results

Two hundred and ten patients (median age 70 years, 68 % male) underwent haemodynamic monitoring within 12 h of AKI I; 85 (41.5 %) progressed to AKI III. The proportion of patients with underlying cardiac disease was significantly higher among progressors versus non-progressors (58 % vs 34 %, respectively; p = 0.001). On the first day of AKI I, progressors had a significantly higher Sequential Organ Failure Assessment score (9 vs 8; p < 0.001), lower cardiac index (median 2.6 vs 3.3 L/min/m2; p < 0.001), higher arterial lactate (2 vs 1.6 mmol/L; p < 0.001), higher central venous pressure (16 vs 13; p = 0.02), lower mean arterial blood pressure (median 71 vs 74 mmHg; p = 0.01) and significantly higher requirement for cardiovascular and respiratory support, but there was no difference in Hb concentration (median 96 g/L in both groups). Multivariable regression analysis showed that heart disease, need for mechanical ventilation, arterial lactate, Sequential Organ Failure Assessment score, central venous pressure and cardiac index on first day of AKI I were independently associated with progression to AKI III. There was no significant difference in the risk of progression between patients with Hb ≤ or >80 g/L, and ≤ or >100 g/L on day of AKI I.

Conclusions

In critically ill patients with AKI stage 1, anaemia was not associated with an increased risk of progression to more severe AKI.
Reviewer acknowledgement
Authors: Doe Chris Q. , Harris William , Shen Kang , Wong Rachel
Published: March 2016

Contributing reviewers

The editors of Neural Development would like to thank all the reviewers who have contributed to the journal in Volume 10 (2015).
Human bone marrow-derived and umbilical cord-derived mesenchymal stem cells for alleviating neuropathic pain in a spinal cord injury model
Authors: Yousefifard Mahmoud , Nasirinezhad Farinaz , Shardi Manaheji Homa , Janzadeh Atousa , Hosseini Mostafa , Keshavarz Mansoor
Published: March 2016

Background

Stem cell therapy can be used for alleviating the neuropathic pain induced by spinal cord injuries (SCIs). However, survival and differentiation of stem cells following their transplantation vary depending on the host and intrinsic factors of the cell. Therefore, the present study aimed to determine the effect of stem cells derived from bone marrow (BM-MSC) and umbilical cord (UC-MSC) on neuropathic pain relief.

Methods

A compression model was used to induce SCI in a rat model. A week after SCI, about 1 million cells were transplanted into the spinal cord. Behavioral tests, including motor function recovery, mechanical allodynia, cold allodynia, mechanical hyperalgesia, and thermal hyperalgesia, were carried out every week for 8 weeks after SCI induction. A single unit recording and histological evaluation were then performed.

Results

We show that BM-MSC and UC-MSC transplantations led to improving functional recovery, allodynia, and hyperalgesia. No difference was seen between the two cell groups regarding motor recovery and alleviating the allodynia and hyperalgesia. These cells survived in the tissue at least 8 weeks and prevented cavity formation due to SCI. However, survival rate of UC-MSC was significantly higher than BM-MSC. Electrophysiological evaluations showed that transplantation of UC-MSC brings about better results than BM-MSCs in wind up of wide dynamic range neurons.

Conclusions

The results of the present study show that BM-MSC and UC-MSC transplantations alleviated the symptoms of neuropathic pain and resulted in subsequent motor recovery after SCI. However, survival rate and electrophysiological findings of UC-MSC were significantly better than BM-MSC.
Attitude and satisfaction of health care providers towards clinical pharmacy services in Ethiopia: A post-deployment survey
Authors: Bilal Arebu Issa , Tilahun Zelalem , Beedemariam Gebremedhin , Ayalneh Belete , Hailemeskel Bisrat , Engidawork Ephrem
Published: March 2016

Background

Clinical pharmacy service has evolved steadily over the past few decades and is contributing to the ‘patient care journey’ at all stages. The service improves safety and effectiveness of medicines, thereby avoiding medication errors. As part of this global shift in pharmacy education and practice, Ethiopian Universities revamped the undergraduate pharmacy curriculum and the first graduates came out in July 2013. These graduates were immediately deployed in public hospital settings, with the ultimate aim of providing clinical pharmacy services. As such an initiative is new to the Ethiopian pharmacy sector, there is a need to do assessment of the health care providers’ perception and satisfaction towards the service.

Methods

A cross-sectional survey using self-administered questionnaire was conducted in six regions and one-city administration of the country. Physicians, Health officers and Nurses working along with the new pharmacy graduates formed the study population. A total of 650 healthcare professionals participated in the study. Data were entered, cleaned and analyzed using appropriate statistical tools.

Results

Majority of the health care providers agreed that clinical pharmacy service could have a significant contribution to the patient care. A large proportion of them (70–90 %) had a positive attitude, although there appeared to be some differences across professions. About 50 % of the professionals were of the opinion that patient care should be left to the health care providers and pharmacists should concentrate on drug products. In addition, the same proportion of respondents said that the setup in their respective hospital was appropriate for provision of clinical pharmacy service. Multivariable analysis indicated that attitude of the health care providers was significantly associated with year of experience.

Conclusions

A large proportion of the health care providers had positive attitude towards the service, although the extent of the service was below their expectation. Hence, efforts should be in place to organize continuous professional training for pharmacists and awareness creation forums for other healthcare professionals.
Evaluation of the wound healing potential of isoquercetin-based cream on scald burn injury in rats
Authors: Bhatia Nitish , Kaur Gursharan , Soni Varinder , Kataria Juhi , Dhawan Ravi K
Published: March 2016

Background

The present study was designed to evaluate the potential of isoquercetin-based cream formulation on scald burn wound injury in rats.

Methods

Four isoquercetin-based cream formulations viz. 0.01, 0.02, 0.04, and 0.06 % w/w were prepared. Cream base and standard anti-burn cream containing silver sulfadiazine were also used for comparison. Scald burn was given to rats by pouring water at 90 °C on a shaved dorsal area of 20 mm2. Deep second-degree burn injury was produced which was evaluated for the next 21 days for the percentage of wound contraction and period of epithelialization. On day 21, the rats were sacrificed and histopathological slides were prepared using hematoxylin-eosin staining. Burned tissue was also screened for levels of oxidative stress using thiobarbituric acid reactive species (TBARS) and reduced glutathione (GSH) estimation.

Results

There was a significant increase in the percentage of wound contraction and a significant decrease in the period of epithelialization in isoquercetin-based cream-treated groups as compared with the control group. However, most significant results were obtained with isoquercetin 0.06 % w/w cream. Histologically, isoquercetin 0.06 % w/w cream treatment resulted in almost complete re-epithelialization and re-structuring of the wound tissue. There was a significant rise in TBARS and a decrease in GSH levels in the burn injury group which was reversed to a major extent by the application of isoquercetin-based cream.

Conclusions

The results indicate the wound healing potential of isoquercetin-based cream. Tissue biochemical studies indicate towards a possible role of free radical scavenging in the observed effects of isoquercetin in wound healing.
Evaluation of Immune-Related Response Criteria and RECIST v1.1 in Patients With Advanced Melanoma Treated With Pembrolizumab
Authors: Hodi F. Stephen , Hwu Wen-Jen , Kefford Richard , Weber Jeffrey S. , Daud Adil , Hamid Omid , Patnaik Amita , Ribas Antoni , Robert Caroline , Gangadhar Tara C. , Joshua Anthony M. , Hersey Peter , Dronca Roxana , Joseph Richard , Hille Darcy , Xue Dahai , Li Xiaoyun Nicole , Kang S. Peter , Ebbinghaus Scot , Perrone Andrea , Wolchok Jedd D.
Published: March 2016

Purpose

We evaluated atypical response patterns and the relationship between overall survival and best overall response measured per immune-related response criteria (irRC) and Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) in patients with advanced melanoma treated with pembrolizumab in the phase Ib KEYNOTE-001 study (clinical trial information: NCT01295827).

Patients and Methods

Patients received pembrolizumab 2 or 10 mg/kg every 2 weeks or every 3 weeks. Atypical responses were identified by using centrally assessed irRC data in patients with ≥ 28 weeks of imaging. Pseudoprogression was defined as ≥ 25% increase in tumor burden at week 12 (early) or any assessment after week 12 (delayed) that was not confirmed as progressive disease at next assessment. Response was assessed centrally per irRC and RECIST v1.1.

Results

Of the 655 patients with melanoma enrolled, 327 had ≥ 28 weeks of imaging follow-up. Twenty-four (7%) of these 327 patients had atypical responses (15 [5%] with early pseudoprogression and nine [3%] with delayed pseudoprogression). Of the 592 patients who survived ≥ 12 weeks, 84 (14%) experienced progressive disease per RECIST v1.1 but nonprogressive disease per irRC. Two-year overall survival rates were 77.6% in patients with nonprogressive disease per both criteria (n = 331), 37.5% in patients with progressive disease per RECIST v1.1 but nonprogressive disease per irRC (n = 84), and 17.3% in patients with progressive disease per both criteria (n = 177).

Conclusion

Atypical responses were observed in patients with melanoma treated with pembrolizumab. Based on survival analysis, conventional RECIST might underestimate the benefit of pembrolizumab in approximately 15% of patients; modified criteria that permit treatment beyond initial progression per RECIST v1.1 might prevent premature cessation of treatment.
Randomized Open-Label Phase II Trial of Apitolisib (GDC-0980), a Novel Inhibitor of the PI3K/Mammalian Target of Rapamycin Pathway, Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma
Authors: Powles Thomas , Lackner Mark R. , Oudard Stéphane , Escudier Bernard , Ralph Christy , Brown Janet E. , Hawkins Robert E. , Castellano Daniel , Rini Brian I. , Staehler Michael D. , Ravaud Alain , Lin Wei , O’Keeffe Bridget , Wang Yulei , Lu Shan , Spoerke Jill M. , Huw Ling-Yuh , Byrtek Michelle , Zhu Rui , Ware Joseph A. , Motzer Robert J.
Published: March 2016

Purpose

To the best of our knowledge, this study is the first to compare dual inhibition of PI3K/mammalian target of rapamycin (mTOR) by apitolisib (GDC-0980) against single inhibition of mTORC1 by everolimus in metastatic renal cell carcinoma (mRCC).

Patients and Methods

Patients with clear-cell mRCC who progressed on or after vascular endothelial growth factor–targeted therapy were randomly assigned to apitolisib 40 mg once per day or to everolimus 10 mg once per day. End points included progression-free survival, safety, overall survival, and objective response rate. Biomarker assessments were conducted.

Results

Eighty-five patients were randomly assigned. After 67 events, stratified analysis revealed that median progression-free survival was significantly shorter for apitolisib than for everolimus (3.7 v 6.1 months; hazard ratio, 2.12 [95% CI, 1.23 to 3.63; P < .01]); apitolisib was not favored in any stratification subgroup. Median overall survival was not significantly different but trended in favor of everolimus (16.5 v 22.8 months; hazard ratio, 1.77 [95% CI, 0.97 to 3.24; P = .06]). The objective response rate was 7.1% for apitolisib and 11.6% for everolimus. Patients administered apitolisib with a greater incidence of grade 3 to 4 adverse events were more likely to discontinue treatment (31% v 12% for everolimus). No drug-related deaths were observed. Apitolisib in comparison with everolimus was associated with substantially more high-grade hyperglycemia (40% v 9%) and rash (24% v 2%). Apitolisib pharmacokinetics suggested a relationship between exposure, and rash and hyperglycemia. Retrospective biomarker analyses revealed a relationship between VHL mutation status and outcome with everolimus but not with apitolisib. High hypoxia-inducible factor 1α protein expression was associated with better outcome in both arms.

Conclusion

This study demonstrated that dual PI3K/mTOR inhibition by apitolisib was less effective than was everolimus in mRCC, likely because full blockade of PI3K/mTOR signaling resulted in multiple on-target adverse events. VHL mutation and hypoxia-inducible factor 1α expression may be predictive of an mTOR inhibitor benefit, although prospective validation is required.
Surgical Proficiency Gain and Survival After Esophagectomy for Cancer
Authors: Markar Sheraz R. , Mackenzie Hugh , Lagergren Pernilla , Hanna George B. , Lagergren Jesper
Published: March 2016

Purpose

We aimed to identify the presence and length of esophagectomy proficiency gain curves in terms of short- and long-term mortality for esophageal cancer.

Patients and Methods

Patients who underwent esophagectomy for esophageal cancer between 1987 and 2010 with follow-up until 2014 were identified from a well-established, population-based, nationwide Swedish cohort study. Proficiency gain curves were created by using risk-adjusted cumulative sum analysis for 30-day, 90-day, 1-year, 3-year, and 5-year all-cause and disease-specific mortality measures. Similarly, the proficiency gain curves for lymph node harvest, resection margin status, and reoperation incidence were assessed as performance-contributing factors to the observed changes in long-term survival.

Results

Esophagectomies in 1,821 patients with esophageal cancer were conducted by 139 surgeons. The change-point in proficiency gain curve for all-cause 30-day mortality was early, at 15 cases, when mortality decreased from 7.9% to 3.1% (P < .001). Later change-points, which ranged from 35 to 59 cases, were observed for 1-, 3- and 5-year mortality rates, for which all-cause mortality decreased from 34.9% to 27.7% (P = .011), from 47.4% to 41.5% (P = .049), and from 31.4% to 19.1% (P = .009), respectively. Similar change-points were observed in disease-specific mortality at 1 and 3 years. There was a continuous increase in lymph node harvest, which did not plateau. Also, change-points were observed for resection margin with tumor involvement at 17 cases, with a reduction from 20.9% to 15.2% (P = .004), and for reoperation rate at 55 cases, with a reduction from 12.6% to 5.0% (P < .001).

Conclusion

The gain of proficiency in esophagectomy for cancer is associated with measurable changes in short- and long-term mortality results. These findings indicate a need for structured national training and mentorship programs for esophageal cancer surgery.
Meta-Analysis Evaluating the Impact of Site of Metastasis on Overall Survival in Men With Castration-Resistant Prostate Cancer
Authors: Halabi Susan , Kelly William Kevin , Ma Hua , Zhou Haojin , Solomon Nicole C. , Fizazi Karim , Tangen Catherine M. , Rosenthal Mark , Petrylak Daniel P. , Hussain Maha , Vogelzang Nicholas J. , Thompson Ian M. , Chi Kim N. , de Bono Johann , Armstrong Andrew J. , Eisenberger Mario A. , Fandi Abderrahim , Li Shaoyi , Araujo John C. , Logothetis Christopher J. , Quinn David I. , Morris Michael J. , Higano Celestia S. , Tannock Ian F. , Small Eric J.
Published: March 2016

Purpose

Reports have suggested that metastatic site is an important predictor of overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC), but these were based on a limited number of patients. We investigate the impact of site of metastases on OS of a substantial sample of men with mCRPC who received docetaxel chemotherapy in nine phase III trials.

Patients and Methods

Individual patient data from 8,820 men with mCRPC enrolled onto nine phase III trials were combined. Site of metastases was categorized as lymph node (LN) only, bone with or without LN (with no visceral metastases), any lung metastases (but no liver), and any liver metastases.

Results

Most patients had bone with or without LN metastases (72.8%), followed by visceral disease (20.8%) and LN-only disease (6.4%). Men with liver metastases had the worst median OS (13.5 months). Although men with lung metastases had better median OS (19.4 months) compared with men with liver metastases, they had significantly worse median survival duration than men with nonvisceral bone metastases (21.3 months). Men with LN-only disease had a median OS of 31.6 months. The pooled hazard ratios for death in men with lung metastases compared with men with bone with or without LN metastases and in men with any liver metastases compared with men with lung metastases were 1.14 (95% CI, 1.04 to 1.25; P = .007) and 1.52 (95% CI, 1.35 to 1.73; P < .0001), respectively.

Conclusion

Specific sites of metastases in men with mCRPC are associated with differential OS, with successive increased lethality for lung and liver metastases compared with bone and nonvisceral involvement. These data may help in treatment decisions, the design of future clinical trials, and understanding the variation in biology of different sites of metastases in men with mCRPC.
An in vitro model of hemogenic endothelium commitment and hematopoietic production
Authors: Yvernogeau L. , Gautier R. , Khoury H. , Menegatti S. , Schmidt M. , Gilles J.-F. , Jaffredo T.
Published: March 2016

Adult-type hematopoietic stem and progenitor cells are formed during ontogeny from a specialized subset of endothelium, named as hemogenic endothelium, via an endothelial-to-hematopoietic transition (EHT) that occurs in the embryonic aorta and the associated arteries. Despite efforts in generating models, little is known about the mechanisms driving endothelial cells to the hemogenic fate and about the subsequent molecular control of the EHT. Here we have designed a stromal line-free controlled culture system utilizing the embryonic pre-somitic mesoderm to obtain large numbers of endothelial cells that subsequently commit into hemogenic endothelium before undergoing EHT. Follow up of the culture for up to twelve days using key molecular markers reveals stepwise commitment into the blood-forming system that is reminiscent of the cellular and molecular changes occurring during hematopoietic development at the level of the aorta. Long-term, single cell imaging, allows tracking the EHT of newly formed blood cells from the layer of hemogenic endothelial cells. By modifying the culture conditions, it is also possible to modulate the endothelial cell commitment or the EHT or to produce smooth muscle cells at the expense of endothelial cells thereby demonstrating the versatility of the cell culture system. This method will improve our understanding of the intimate cellular changes associated with hemogenic endothelium commitment and EHT and, by unfolding these earliest steps of the hematopoietic program, will pave the way for future ex vivo production of blood cells.