bluuebunny/crossref_metadata_2025 huggingface dataset:
Defibrotide: An Oligonucleotide for Sinusoidal Obstruction Syndrome
Authors: Aziz May T. , Kakadiya Payal P. , Kush Samantha M. , Weigel Kylie , Lowe Denise K.
Published: September 2017

Objective: To review the efficacy and safety of defibrotide as well as its pharmacology, mechanism of action, pharmacokinetics (PK), drug-drug interactions, dosing, cost considerations, and place in therapy. Data Sources: A PubMed search was performed through August 2017 using the terms defibrotide, oligonucleotide, hepatic veno-occlusive disease (VOD), sinusoidal obstruction syndrome (SOS), and hematopoietic cell transplantation (HCT). Other data sources were from references of identified studies, review articles, and conference abstracts plus manufacturer product labeling and website, the Food and Drug Administration website, and clinicaltrials.gov. Study Selection and Data Extraction: English-language trials that examined defibrotide’s pharmacodynamics, mechanism, PK, efficacy, safety, dosing, and cost-effectiveness were included. Data Synthesis: Trials have confirmed the safety and efficacy of defibrotide for treatment of VOD/SOS in adult and pediatric HCT patients, with complete response rates and day +100 overall survival rates ranging from 25.5% to 76% and 35% to 64%, respectively. The British Committee for Standards in Haematology/British Society for Blood and Marrow Transplantation Guidelines recommend defibrotide prophylaxis in pediatric and adult HCT patients with risk factors for VOD/SOS; however, its prophylactic use in the United States is controversial. Although there are efficacy data to support this strategy, cost-effectiveness data have not shown it to be cost-effective. Defibrotide has manageable toxicities, with low rates of grade 3 to 4 adverse effects. Conclusions: Defibrotide is the first medication approved in the United States for the treatment of adults and children with hepatic VOD/SOS, with renal or pulmonary dysfunction following HCT. Data evaluating defibrotide for VOD/SOS prevention are conflicting and have not shown cost-effectiveness.
Evaluation of Expression Level of Apolipoprotein M as a Diagnostic Marker for Primary Venous Thromboembolism
Authors: Ahmad Abrar , Sundquist Kristina , Zöller Bengt , Dahlbäck Björn , Elf Johan , Svensson Peter J. , Strandberg Karin , Sundquist Jan , Memon Ashfaque A.
Published: September 2017

Recently, decreased levels of apolipoprotein M (ApoM) were shown to be associated with higher risk of recurrent venous thromboembolism (VTE) in male patients. However, the role of ApoM in primary VTE is unknown. We aimed in our study to analyze the plasma levels of ApoM in patients with VTE in order to evaluate the diagnostic importance of ApoM in primary VTE. A total of 357 patients with suspected first episode of VTE were recruited prospectively in the SCORE study. Plasma samples from 307 patients were available for quantifying the plasma levels of ApoM in patients with VTE using sandwich enzyme-linked immunosorbent assay method. Among the whole population, plasma levels (mean [standard deviation]) of ApoM were not significantly different between patients with VTE (0.72 [0.20]) and non-VTE patients (0.72 [0.16]), P = .99. Similarly, in regression analyses, no significant association of ApoM plasma levels with the risk of VTE was found on univariate (odds ratio [OR] =1.0, 95% confidence interval [CI] 0.21-4.84, P = .99) and multivariate analysis (OR = 1.25, 95% CI = 0.19-8.34, P = .819) after adjusting for age, body mass index, and smoking. Moreover, results did not differ significantly after stratification of data according to sex ( P > .05). In this study, our results do not suggest a diagnostic role for ApoM plasma levels in patients with primary VTE. Moreover, the current study suggests that role of ApoM as a risk factor may differ for primary VTE and recurrent VTE in male patients.
Sedentariness and weight status related to SES and family characteristics in Italian adults: exploring geographic variability through multilevel models
Authors: Matranga Domenica , Tabacchi Garden , Cangialosi Donatella
Published: September 2017

Aim: In this study, our aim was to assess the prevalence of sedentariness and overweight/obesity, two modifiable risk factors for non-communicable diseases (NCDs), and to investigate the geographic variability in their association with socio-economic status (SES) and family characteristics in Italian adults. Methods: The Multipurpose Survey on Health Conditions and the Recourse to Health Services (MSHC), 2012/2013 edition, conducted by the National Institute of Statistics was used as data source. The sample for this study included 99,479 interviewed people aged 18 and over, which are representative of about 50 million persons. For the scope of this analysis, data were considered as individuals nested within families within regions and analysed through multilevel models. Results: It was estimated that 39.8% of Italian adults are sedentary, 38.1% are partially active and 22.1% are physically active; 11.3% of Italian adults are obese and the 34.5% are overweight. There was evidence of inverse socio-economic gradient for both sedentariness and body mass index (BMI). There was higher risk of sedentariness for one-parent (odds ratio (OR) = 1.10; 95% confidence interval (CI) = (1.02; 1.20)) and other family types (OR = 1.34; 95% CI = (1.20; 1.48 )) compared with couples with children. Also, the relative variation of BMI was statistically significant for one-parent, one-person and other families ( p < 0.05). An increasing north–south gradient was suggested for BMI, but not for sedentariness. Conclusions: Policy interventions could be addressed to reduce BMI levels in the southern area and to encourage physical activity in regions with high sedentariness. The Italian family is the key driver to promote virtuous healthy behaviours.
Risk literacy: Concepts and pedagogical implications for early childhood education
Authors: Nikiforidou Zoi
Published: September 2017

Taking risks and enjoying challenges are fundamental to the lives of young children from a developmental and evolutionary point of view. However, in modern societies, increasing concern about dangers and injuries has led to the escalation in regulation and provisions for the safety of young children. This intent to establish secure and risk-free environments for young children reaches, in some cases, the other end of the spectrum – that of overprotection, constraining children’s drive to explore, dare and experiment. This article explores the relationship between children and risk by focusing on the processes of thinking and acting, drawing on positive and negative discourses around risk. The article proposes that more interest should be directed towards enabling children’s own knowledge and understanding of risk, through early childhood education and risk literacy. The use of graphical representations, children’s probabilistic and possibility thinking, the risk culture of the classroom and a cross-curricular approach are pedagogical implications that could inform policy and practice in early childhood education aiming at present and future agents who are risk literate.
Beyond the mogul: From media conglomerates to portfolio media
Authors: Noam Eli
Published: September 2017

The article shows that outside ownership of media moves in stages – from media properties as the mouthpiece for personal and business interests, to a second stage of conglomerates seeking economic “synergies” of performance, to a third stage dominated by financial portfolio diversification. These phases of outside media ownership correspond to the stages of economic development in that country.The article finds that in rich countries, the ownership of media by industrial companies as a way to create political influence has been declining. The second phase, based on economic synergies, has become a less significant driver, too. On the other hand, there has been a significant growth of cross-ownership through financial intermediaries. In contrast, the media systems of emerging and developing countries are still operating in the first two phases of cross-ownership, centered on projection of influence and on conglomerate business synergies.It is quite likely that these dynamics will lead to a “capture gap” between emerging and rich societies. Media in the former would be significantly more captured through the seekers of personal influence and conglomerate synergies, while media in the latter are subject to professional investors imperatives of profitability, growth, predictability, and fit into portfolio diversification. The same financial institutions from rich countries are also likely to seek acquisitions in the emerging markets by leapfrogging the two other stages. The likely responses are restrictions on foreign ownership of media. Domestic conglomerates will step in and assume control. Media capture will then become patriotic.The article is fact-based and provides details on the media assets of non-media companies in 26 countries accounting for about 60% of the world’s population and over 80% of its economy.
Hot surface pre-ignition in direct-injection spark-ignition engines: Investigations with Tailor-Made Fuels from Biomass
Authors: Budak Oguz , Hoppe Fabian , Heuser Benedikt , Pischinger Stefan , Burke Ultan , Heufer Alexander
Published: September 2017

Two promising alternative fuel candidates for spark-ignition engines, 2-butanone and 2-methylfuran, have been identified in the context of the Cluster for Excellence ‘Tailor-Made Fuels from Biomass’. To further explore the potential of these fuels for spark-ignition engine application, experimental and numerical investigations into the occurrence of the abnormal combustion phenomenon of hot surface–induced pre-ignition have been conducted, with pure ethanol, RON97 E10, and pure iso-octane as reference fuels. For the experimental investigations, a single-cylinder engine with a compression ratio of 11, equipped with a glow-plug to create a hot spot in the cylinder, was operated at 1500 r/min and 1500 mbar charge pressure. Each fuel was tested with several glow-plug temperatures until a minimum pre-ignition frequency of 2% was observed. The results show that 2-methylfuran reaches its 2% pre-ignition frequency at a glow-plug temperature of 880 °C, which is 16 °C higher than the 2% pre-ignition frequency of ethanol at 864 °C and 10 °C less than RON97 E10 with 890 °C. Iso-octane showed the lowest pre-ignition resistance with a 2% pre-ignition frequency at a glow-plug temperature of 853 °C, and 2-butanone was most resistant against pre-ignition in this study with a 2% pre-ignition frequency at 932 °C. Further numerical investigations, including zero-dimensional ignition delay time calculations and three-dimensional computational fluid dynamics simulations, revealed a clear connection between the surface ignition frequency of these fuels and their reaction kinetics.
Qualitative inquiry using social media: A field-tested example
Authors: Caplan Mary A , Purser Gregory
Published: September 2017

Social media is a rapidly expanding set of technology tools that people use to communicate, learn, interact, document, create, and participate in societies worldwide. It is also transforming how social work, among other professions, conducts qualitative research. This study outlines a field-tested method used to analyze data from Reddit, a major social media platform used by 6% of online adults in the United States. It provides a step-by-step account of a Reddit-based qualitative thematic analysis from a social work heuristic lens on the subject of poverty. To our knowledge, no such account of mining social media big data from Reddit for social work practice exists in the literature. Philosophical, ethical, and practical considerations of this method are discussed.
Micro-cracking monitoring and fracture evaluation for crumb rubber concrete based on acoustic emission techniques
Authors: Xu Jie , Fu Zhengwu , Han Qinghua , Lacidogna Giuseppe , Carpinteri Alberto
Published: September 2017

A micro-cracking monitoring and fracture evaluation method for crumb rubber concrete based on the acoustic emission technique was developed. The precursory micro-cracking activity and fracture behavior of crumb rubber concrete with different rubber contents, 0%, 10%, and 15%, were analyzed. The various acoustic emission statistical parameters including cumulative event, frequency distribution, amplitude distribution, and b-value were used for the analysis. The general fracture process is similar for all normal and crumb rubber concretes and can be divided into three distinct stages of micro-crack activity, namely, early stage, main collapse stage, and post-fracture stage. The following conclusions were drawn from the analysis: (1) more micro-cracks initiated and grew at early stage in the normal concrete, while less micro-cracks in the crumb rubber concrete but with longer stage duration; (2) the duration and crack number are both increasing with the increase in the rubber contents in main collapse and post-fracture stages; (3) new crack types associated with the rubber particles were recorded due to the change of the peak frequencies; and (4) the amplitude of the cracks decrease with the increase in the rubber content due to the damping ratio and interface improvement by the mixed rubbers. The results obtained in this article demonstrate that the acoustic emission technique can provide valuable information for a better understanding of micro-cracking and fracture monitoring of crumb rubber concrete.
Who Are the Victims and Who Are the Perpetrators in Dating Violence? Sharing the Role of Victim and Perpetrator
Authors: Park Sihyun , Kim Sin-Hyang
Published: September 2017

Background:

Dating violence (DV) is a serious problem with devastating consequences. Often, research on DV has focused on two distinct groups: victims and perpetrators. However, there is growing evidence for a victim–perpetrator overlap model, which posits that those involved in DV are more likely to take on both roles, rather than either role on its own.

Purpose:

We investigated the patterns of involvement in DV among those who identified themselves as victims or perpetrators in previous studies.

Method:

This was a systematic review and meta-analysis. A total of 371 variables related to participants’ previous and concurrent experiences of DV victimization or perpetration (202 variables related to victimization and 169 related to perpetration) were identified in 25 studies, which were found by systematically searching three databases: PubMed, Web of Science, and SCOPUS.

Results:

The majority of previous studies categorized study participants as either DV victims or perpetrators; however, those who identified themselves as either DV victims or DV perpetrators were more likely to assume the opposite role as well. Specifically, current DV perpetrators had a strong association with previous or concurrent victimization experiences, and current DV victims were similarly likely to have assumed the roles of both victim and perpetrator in their histories.

Conclusion:

Further efforts should be put into avoiding categorization of those involved in violence; rather, they should be regarded as a single group. Additionally, evidence-based interventions should be developed for this population to help break the cycle of violence.
Targeting Body Compassion in the Treatment of Body Dissatisfaction: A Case Study
Authors: Altman Jennifer K. , Zimmaro Lauren A. , Woodruff-Borden Janet
Published: September 2017

Mindfulness and acceptance-based cognitive-behavioral therapies (MAB CBTs) are increasingly used in the treatment of body image disturbances. This case report describes an adjunct treatment component targeting body compassion in the course of an MAB CBT for an individual with body dissatisfaction. Body compassion is a new body-focused mindfulness and acceptance-based (MAB) construct that specifically describes the facets of the relationship individuals have with their bodies. The course of treatment included the originally planned MAB CBT protocol plus the additive component for five weekly 50-min individual sessions. During these sessions, body compassion was the primary treatment target. This phase of treatment utilized cognitive defusion, mindfulness, and self-compassion exercises. Over the course of this phase of treatment, the patient’s body compassion and body image flexibility significantly improved. The patient’s presenting symptoms also abated. Improvements were maintained at 1-, 3-, and 18-month follow-up time points. This case study illustrates several clinical strategies and provides initial support for body compassion as a viable treatment target for individuals struggling with body dissatisfaction.
MicroRNAs as biomarkers for clinical studies
Authors: Pogribny Igor P
Published: September 2017

The development of better diagnostic and prognostic non-invasive biomarkers holds an enormous potential to improve the ability to diagnose and individualize treatment of a great number of human diseases and substantially reduce health care cost. The discovery of a fundamental role of microRNAs in the disease pathogenesis and their presence and stability in biological fluids has led to extensive investigation of the role of microRNAs as potential non-invasive biomarkers for disease diagnosis and prognosis. The result of this research has suggested that alterations of microRNAs may be sensitive indicators of various pathologies; however, despite the indisputable progress in this field, the diagnostic promise of microRNAs has remained a work in progress, and circulating microRNAs have not entered the field of clinical medicine yet. Commonly reported microRNAs as disease biomarkers are largely not disease-specific and the results are often contradicting in independent studies. This review summarizes the current knowledge on the role of microRNAs as disease indicators and emphasizes the current gaps, challenges, and questions that need to be addressed in future well-designed and well-controlled studies for a successful translation of microRNA profiling into clinically meaningful tests.

Impact statement

This review summarizes the current knowledge on the role of circulating miRNAs as clinical diagnostic biomarkers and highlights the challenges that need to be addressed in future studies for a successful translation of circulating miRNAs into a novel diagnostic tool.
Alterations in circadian and meal-induced gut peptide levels in lean and obese rats
Authors: Moghadam Alexander A , Moran Timothy H , Dailey Megan J
Published: September 2017

Alterations in gut hormone signaling are a likely contributing factor to the metabolic disturbances associated with overweight/obesity as they coordinate the timing of feeding behavior, absorption, and utilization of nutrients. These hormones are released in response to food intake, or follow a circadian or anticipatory pattern of secretion that is independent of nutrient stimulation. The aim of this study was to identify the degree to which high-fat diet-induced obesity would alter the daily rhythm of gut peptide plasma levels (glucagon-like peptide-1 [GLP-1], peptide YY [PYY], insulin or amylin [AMY]) or meal-induced levels in the middle of the light or dark cycle. Male Sprague-Dawley rats were fed a high-fat diet (OBESE) or chow (LEAN), implanted with jugular catheters, and blood samples were taken every 2 h throughout the light/dark cycle while freely feeding or after an Ensure liquid meal. We found that even when OBESE and LEAN animals ate the same kcals and have a similar pattern of food intake, there is a difference in both the levels and rhythm of plasma gut peptides. GLP-1 and PYY are higher during the light cycle in LEAN animals and AMY is higher in the OBESE group throughout the light/dark cycle. There was also a differential response of plasma gut signals after the Ensure meal, even though the composition and amount of intake of the meal were the same in both groups. These changes occur prior to the high-fat diet induced loss of glycemic control and may be a target for early intervention.

Impact statement

The aim of this study was to test if obesity would alter the daily rhythm of gut peptides or meal-induced levels in the middle of the light or dark cycle. We found that even when animals are eating the same amount (in kcal) of food that the obese animals have altered daily rhythms and meal-induced gut peptide levels. In particular, we are the first to show that obesity induces increases in peptide YY levels during the light cycle and amylin remains high throughout the light and dark cycle in obese animals. These changes occurred prior to a loss of glycemic control. Thus, the rhythm of gut peptides could be used as an early indicator of later and more serious metabolic disturbances and may be a target for early intervention.
Improving quality and outcomes of stroke care in hospitals: Protocol and statistical analysis plan for the Stroke123 implementation study
Authors: Cadilhac Dominique A , Andrew Nadine E , Kilkenny Monique F , Hill Kelvin , Grabsch Brenda , Lannin Natasha A , Thrift Amanda G , Anderson Craig S , Donnan Geoffrey A , Middleton Sandy , Grimley Rohan
Published: September 2017

Rationale

The effectiveness of clinician-focused interventions to improve stroke care is uncertain.

Aims

To determine whether an organizational intervention can improve the quality of stroke care over usual care.

Sample size estimates

To detect an absolute 10% difference in overall performance (composite outcome), a minimum of 21 hospitals and 843 patients per group was determined.

Methods and design

Before and after controlled design in hospitals in Queensland, Australia.

Intervention

Externally facilitated program (StrokeLink) using outreach workshops incorporating clinical performance feedback, patient outcomes (survival, quality of life at 90–180 days), local barrier assessments to best practice care, action planning, and ongoing support. Descriptive and multivariable analyses adjusted for patient correlations by hospital (intention-to-treat method).

Context

Concurrent implementation of financial incentives to increase stroke unit access and use of the Australian Stroke Clinical Registry for performance monitoring.

Study outcome(s)

Primary outcome: net change in composite score (i.e. total number of process indicators achieved divided by the sum of eligible indicators for each cohort). Secondary outcomes: change in individual indicators, change in composite score comparing hospitals that did or did not develop action plans (per-protocol analysis), impact on 90–180-day health outcomes. Sensitivity analyses: hospital self-rated status, alternate cross-sectional audit data (Stroke Foundation). To account for temporal effects, comparison of Queensland hospital performance relative to other Australian hospitals will also be undertaken.

Discussion

Twenty-one hospitals were recruited; however, one was unable to participate within the study time frame. Workshops were held between 11 March 2014 and 7 November 2014. Data are ready for analysis.
Risk Factors for Reoperation and Performance-Based Outcomes After Operative Fixation of Foot Fractures in the Professional Athlete: A Cross-Sport Analysis
Authors: Singh Sameer K. , Larkin Kevin E. , Kadakia Anish R. , Hsu Wellington K.
Published: September 2017

Background:

Professional athletes are predisposed to fractures of the foot due to large stresses placed on the lower extremity. These players are concerned with efficiently returning to play at a high level. Return-to-play rates after operative treatment have been previously reported, yet performance outcomes after such treatment are generally unknown in this population.

Hypothesis:

Overall, professional athletes sustaining a foot fracture would return to play at high rates with little impact on postoperative performance or league participation. However, National Football League (NFL) athletes would have a significantly greater decline in performance due to the high-impact nature of the sport.

Study Design:

Case series.

Level of Evidence:

Level 4.

Methods:

Athletes in the National Basketball League (NBA), NFL, Major League Baseball (MLB), and National Hockey League (NHL) undergoing operative fixation of a foot fracture were identified through a well-established protocol confirmed by multiple sources of the public record. Return-to-play rate and time to return were collected for each sport. League participation and game performance data were collected before and after surgery. Statistical analysis was performed, with significance accepted as P ≤ 0.05.

Results:

A total of 77 players undergoing 84 procedures met the inclusion criteria. Overall, 98.7% (76/77) of players were able to return to play, with a median time to return across all sports of 137 days. Players returned to preoperative performance levels within 1 season of surgery. Six players (7.8%) sustained refracture requiring reoperation, all of whom were in the NBA. Percentage of games started during the season after primary operative treatment was a predictive factor for reinjury (99% vs 40%, P = 0.001).

Conclusion:

Athletes returned to play at a high rate after foot fracture fixation, with excellent postoperative performance levels, regardless of sport and fracture location. NBA athletes sustaining fifth metatarsal and navicular fractures are at greater risk of reinjury compared with other athletes. Returning to high levels of athletic participation soon after surgery may predispose athletes to refracture and subsequent reoperation.

Clinical Relevance:

Players, coaches, and team physicians should be aware of the impact of foot fractures on career performance and longevity to best guide therapy.
Quantitative diffusion tensor imaging analysis does not distinguish pediatric canines with mucopolysaccharidosis I from control canines
Authors: Middleton Dana M , Li Jonathan Y , Chen Steven D , White Leonard E , Dickson Patricia I , Matthew Ellinwood N , Provenzale James M
Published: September 2017

Purpose

We compared fractional anisotropy and radial diffusivity measurements between pediatric canines affected with mucopolysaccharidosis I and pediatric control canines. We hypothesized that lower fractional anisotropy and higher radial diffusivity values, consistent with dysmyelination, would be present in the mucopolysaccharidosis I cohort.

Methods

Six canine brains, three affected with mucopolysaccharidosis I and three unaffected, were euthanized at 7 weeks and imaged using a 7T small-animal magnetic resonance imaging system. Average fractional anisotropy and radial diffusivity values were calculated for four white-matter regions based on 100 regions of interest per region per specimen. A 95% confidence interval was calculated for each mean value.

Results

No difference was seen in fractional anisotropy or radial diffusivity values between mucopolysaccharidosis affected and unaffected brains in any region. In particular, the 95% confidence intervals for mucopolysaccharidosis affected and unaffected canines frequently overlapped for both fractional anisotropy and radial diffusivity measurements. In addition, in some brain regions a large range of fractional anisotropy and radial diffusivity values were seen within the same cohort.

Conclusion

The fractional anisotropy and radial diffusivity values of white matter did not differ between pediatric mucopolysaccharidosis affected canines and pediatric control canines. Possible explanations include: (a) a lack of white matter tissue differences between mucopolysaccharidosis affected and unaffected brains at early disease stages; (b) diffusion tensor imaging does not detect any existing differences; (c) inflammatory processes such as astrogliosis produce changes that offset the decreased fractional anisotropy values and increased radial diffusivity values that are expected in dysmyelination; and (d) our sample size was insufficient to detect differences. Further studies correlating diffusion tensor imaging findings to histology are warranted.
Extra-axial cerebrospinal fluid spaces in children with benign external hydrocephalus: A case-control study
Authors: Hussain Zaamin B , Hussain Amaani B , Mitchell Patrick
Published: September 2017

Background

The distinction between normal and pathological extra-axial cerebrospinal fluid (CSF) spaces is unclear, with the use of the term benign external hydrocephalus (BEH) not being well defined in clinical practice. This study aimed to establish a distribution of metrics of the subarachnoid space in a population of children diagnosed as normal, and investigate the clinical use of the term BEH.

Methods

A retrospective case-control study on magnetic resonance image scans was performed on 150 children diagnosed as normal and 10 children diagnosed with BEH. Measurements were taken in the axial plane for CSF width (CSFW), and interhemispheric width (IHW).

Results

Normal controls had a mean age of 11.1 ± 7.6 months (78 male, 72 female) and the BEH sample had a mean age of 10.6 ± 7.8 months (six male, four female). Mean CSFW was 7.96 ± 4.79 mm in the BEH sample compared to 4.58 ± 2.25 mm in the normal sample ( p < 0.05). Mean IHW was 6.30 ± 2.79 mm in the BEH sample compared to 3.89 ± 1.83 mm in the normal sample ( p < 0.05). However, a substantial overlap between the two distributions of CSFW was found, with 50% of BEH patients lying within a single standard deviation of the mean of normal individuals.

Conclusion

The absence of diagnostic criteria for BEH means reporting is variable. Patients being diagnosed with BEH who have no other clinical defects may represent the extreme of the normal population rather than a distinct clinical entity.
Novel insights into the clinical phenotype and pathophysiology underlying low VWF levels
Authors: Lavin Michelle , Aguila Sonia , Schneppenheim Sonja , Dalton Niall , Jones Kenneth L. , O’Sullivan Jamie M. , O’Connell Niamh M. , Ryan Kevin , White Barry , Byrne Mary , Rafferty Marie , Doyle Mairead M. , Nolan Margaret , Preston Roger J. S. , Budde Ulrich , James Paula , Di Paola Jorge , O’Donnell James S.
Published: September 2017

Key Points

Patients registered with low VWF have significant bleeding phenotypes that cannot be explained by concomitant bleeding disorders. Low VWF levels in the range of 30 to 50 IU/dL are predominantly due to reduced VWF synthesis/secretion rather than enhanced clearance.
Pooled Analysis Safety Profile of Nivolumab and Ipilimumab Combination Therapy in Patients With Advanced Melanoma
Authors: Sznol Mario , Ferrucci Pier Francesco , Hogg David , Atkins Michael B. , Wolter Pascal , Guidoboni Massimo , Lebbé Celeste , Kirkwood John M. , Schachter Jacob , Daniels Gregory A. , Hassel Jessica , Cebon Jonathan , Gerritsen Winald , Atkinson Victoria , Thomas Luc , McCaffrey John , Power Derek , Walker Dana , Bhore Rafia , Jiang Joel , Hodi F. Stephen , Wolchok Jedd D.
Published: September 2017

Purpose

The addition of nivolumab (anti–programmed death-1 antibody) to ipilimumab (anti–cytotoxic T-cell lymphocyte–associated 4 antibody) in patients with advanced melanoma improves antitumor response and progression-free survival but with a higher frequency of adverse events (AEs). This cross-melanoma study describes the safety profile of the approved nivolumab plus ipilimumab regimen.

Methods

This retrospective safety review on data from three trials (phase I, II, and III) included patients with advanced melanoma who received at least one dose of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks × 4 and then nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity while following established guidelines for AE management. Analyses were of all treatment-related AEs, select (immune-related) AEs, time to onset and resolution, and use of immune-modulating agents and their effects on outcome.

Results

Among 448 patients, median duration of follow-up was 13.2 months. Treatment-related grade 3/4 AEs occurred in 55.5% of patients; 35.7% had treatment-related AEs that led to discontinuation. The most frequent treatment-related select AEs of any grade were skin (64.3%) and GI (46.7%) and of grade 3/4, hepatic (17.0%) and GI (16.3%); 30.1% developed a grade 2 to 4 select AE in more than one organ category. Median time to onset of grade 3/4 treatment-related select AEs ranged from 3.1 (skin) to 16.3 (renal) weeks, and with the exclusion of endocrine AEs, median time to resolution from onset ranged from 1.9 (renal) to 4.5 (pulmonary) weeks, with resolution rates between 79% and 100% while using immune-modulating agents. Four (< 1%) on-study deaths were attributed to therapy.

Conclusion

Frequency of grade 3/4 treatment-related AEs was higher with nivolumab plus ipilimumab and occurred earlier than historical experience with either agent alone, but resolution rates were similar.
The expression ofLdh-cin the skeletal muscle of plateau pika (Ochotona curzoniae) enhances adaptation to a hypoxic environment
Authors: An Zhi F. , Wei Deng B. , Wei Lian , Wang Yang , Wei Lin N.
Published: September 2017

The plateau pika (Ochotona curzoniae) is a species of sprint-running alpine animals in the Qinghai-Tibet Plateau, which is a harsh highland hypoxic environment. Ldh-c is expressed in the testis, sperm and somatic tissues of plateau pika. To reveal the role and physiological mechanisms of sperm-specific lactate dehydrogenase (LDH-C4), in plateau pika to adapt to hypoxic environment, an adenoviral line of pMultiRNAi-Ldhc was constructed and injected into the bilateral biceps femoris of the hind legs. The swimming times of the pikas, and the Ldh-c expression levels, total LDH activities and ATP levels in skeletal muscle, were measured after the pikas were raised in the trapped site for 5 days. Our results showed that after Ldh-c was silenced, the sprint-running ability (swimming time) of the plateau pikas was significant decreased, and the total LDH activities and ATP levels were reduced by 28.21% and 27.88%, respectively. Our results indicated that expression of Ldh-c in the skeletal muscle of plateau pika increased anaerobic glycolysis and enhanced adaptation to highland hypoxic environments.
Nurse honeybee workers tend capped-brood, which does not require feeding, around-the-clock
Authors: Nagari Moshe , Brenner Yafit , Bloch Guy
Published: September 2017

“Nurse” honeybees tend brood around-the-clock with attenuated or no circadian rhythms, but the brood signals inducing this behavior remain elusive. We first tested the hypothesis that worker circadian rhythms are regulated by brood pheromones. We monitored locomotor activity of individually isolated nurse bees that were either exposed to various doses of larval extracts or synthetic brood ester pheromone (BEP). Bees orally treated with larvae extracts showed attenuated circadian rhythms in one of four tested colonies; a similar but statistically non-significant trend was seen in two additional colonies. Nurse bees treated with synthetic BEP showed rhythm attenuation in one of three tested colonies. Next, we tested the hypothesis that capped brood, which does not require feeding, nevertheless induces around-the-clock activity in nurses. By combining a new protocol that enables brood care by individually isolated nurse bees, detailed behavioral observations, and automatic high resolution monitoring of locomotor activity, we found that isolated nurses tended capped brood around-the-clock with attenuated circadian rhythms. Bees individually isolated in similar cages but without brood, showed strong circadian rhythms in locomotor activity and rest. This study shows for the first time that the need to feed hungry larvae is not the only factor accounting for around-the-clock activity in nurse bees. Our results further suggest that the transition between activity with and without circadian rhythms is not a simple switch triggered by brood pheromones. Around-the-clock tending may enhance brood development and health in multiple ways that may include improved larval feeding, thermoregulation and hygienic behavior.
Frank-Starling mechanism and short-term adjustment of cardiac flow
Authors: Chaui-Berlinck José Guilherme , Monteiro Luiz Henrique Alves
Published: September 2017

The Frank-Starling Law of the heart is a filling-force mechanism (FFm), a positive relationship between the distension of a ventricular chamber and its force of ejection, and such a mechanism is found across all the studied vertebrate lineages. The functioning of the cardiovascular system is usually described by means of the cardiac and vascular functions, the former related to the contractility of the heart and the latter related to the after-load imposed to the ventricle. The crossing of these functions is the so-called operation point, and the FFm is supposed to play a stabilizing role for the short-term variations in the working of the system. In the present study, we analyze whether the FFm is truly responsible for such a stability within two different settings: one-ventricle and two-ventricle hearts. To approach the query, we linearized the region around an arbitrary operation point and put forward a dynamical system of differential equations to describe the relationship among volumes in face of blood flows governed by pressure differences between compartments. Our results show that the FFm is not necessary to give stability to an operation point. Thus, what forces might have selected and maintained such a mechanism in all vertebrates? The present results indicate three different and complementary roles for the filling-force mechanism: (1) it decreases the demands of a central controlling system over the circulatory system; (2) it smooths out perturbations in volumes; and (3) it guarantees faster transitions between operation points, i.e., it allows for rapid changes in cardiac output.
Twenty-four years of the Centre for Physical Anthropology
Authors: Kaarma Helje , Veldre Gudrun , Saluste Liidia , Lintsi Mart , Kasmel Jaan , Tiit Ene-Margit , Stamm Raini , Toomsalu Maie
Published: September 2017

The article provides an overview of the activities of the Centre for Physical Anthropology at the University of Tartu from its foundation in 1993 to the present.
Correlation of variations in geocosmic processes and thinking parameters
Authors: Volchek Olga D.
Published: September 2017

Earlier we discovered gender-specific multiyear variations in functional brain asymmetry (FBA) indices, synergistic with variations in geocosmic processes [Volchek, 2013]. FBA serves as a foundation for different types of learning, perception and processing of information. In its turn, type of learning dominating in society manifests itself in social processes, cultural events and working styles of inventors and artists. The purpose of this work was to study thinking and musical creativity indices in relation to geocosmic processes. With Torrance method, we collected data about logical, intuitive and combined thinking styles in over 3400 citizens of St. Petersburg, Russia, born in 1930–1991. Gender-specific daily, seasonal and multiyear variations in thinking indices were revealed at p≤0.001. Content analysis of 3352 Soviet songs and romances composed in 1935–1982 showed evolution of musical thinking.Of special interest is the data on multiyear variations in thinking indices in relation to geocosmic conditions. Significant and reliable variations in thinking types were discovered. For instance, the highest scores for logical thinking type (114.2) were found in men born in 1956, while the lowest scores (82.6) were found in men born in 1959, p≤0.001. According to the results of correlation analysis for the periods of 1940–1991 and 1946–1991, there are correlations between variations in thinking types and geocosmic indices. The most influential factors are Earth’s rotation rate ERR and interplanetary magnetic field IMF. With these indices rising in year of birth and preceding year, scores for left-brain logical thinking type increase, p≤0.001.Conclusion: geocosmic processes influence coordination and activation of human brain hemispheres, as well as leading thinking type in society and evolution of music. Such phenomena can be reflected in social processes up to emerge of periods of so-called Thaw or Cold war.
PUBLIC PROCUREMENT IN TERMS OF THE EURASIAN ECONOMIC UNION
Authors: Кабытов Павел , Kabytov Pavel
Published: September 2017

The realization of the goals of the Eurasian economic Union is closely connected with the formation of common markets in various areas of economic cooperation. One of these areas are public procurement, which can have a significant impact on mutual trade between the member States in the framework of the functioning of the internal market of the Eurasian economic Union. To date, however, this effect is not significant. Prerequisites for this are the numerous “barriers”, “withdrawal” and “restrictions” that remain in the legislation of member States of the Eurasian economic Union, which requires its identify and resolve.
The purpose of this study was to identify obstacles to the formation of a single public procurement market in the Eurasian economic Union. The objective of the study is the analysis of legal regulation of public procurement in member States of the Eurasian economic Union and the Eurasian economic Union with the aim of identifying the existing “barriers”, “withdrawal” and “limitations” in this field.
To achieve the goals and objectives of the study are applied comparative legal, formal legal and formal logical methods, method of interpretation of law, as well as scientific methods.
The results of the study identified obstacles to providing a high level of cross-border participation in public procurement. Revealed that the provision of unhindered access for potential suppliers and providers of member States to participate in public procurement is in direct proportion to ensure the regime of the single market for services in various service sectors. It is concluded that a necessary condition for the formation of a single market of public procurement is not only elimination of the existing “barriers”, “exceptions” and “limits” in the laws of the member States of the Eurasian economic Union, but also the completion of the process of building a single market for services, the further rapprochement of licensing systems, harmonization of mandatory rules and requirements in the member States of the Eurasian economic Union.
ON THE QUESTION OF POSSIBILITY TO INTRODUCE IN RUSSIA A CRIMINAL LIABILITY AND CRIMINAL PUNISHMENTS OF LEGAL ENTITIES (COMPARATIVE ASPECT)
Authors: Артемов Владислав , Artemov Vladislav
Published: September 2017

The article is devoted to a problem that causes a lot of controversy in a Russian scientific community at present: the possibility and expediency of introducing in Russia the institute of criminal liability of legal persons. The author underlines the problems of this issue. The main arguments of both supporters and opponents of criminal liability of legal persons are presented. Among the main arguments against – the question of personal guilt, which is a major problem and an obstacle to the introduction of this institute, the possibility of tightening the liability of legal persons in other branches of law, etc. Among the main supporting arguments of legal entities’ the criminal liability, referred to in this article, there are international obligations of the Russian Federation, greater efficiency of criminal sanctions, criminal record of legal persons, judicial optimization and others. Attention is also paid to the fact that since 2002 in the Russian Federation there has already existed administrative liability of legal persons, which was one of the major novelties of the Administrative Code, 2002. Russian administrative scholars have formulated the theoretical and practical bases of administrative liability of legal persons that can be used and the introduction of criminal liability of legal persons. In addition, attention is paid to the current debate in Russia on the possible introduction of the category of criminal offence and the possible merging of criminal liability and administrative liability in one single form of legal liability. In this connection it may be interesting to refer to the French experience, where are three categories of offences: crime, délit and contravention.
At the end of the article the author points out the objective difficulties of the possible introduction into the domestic legal system the institute of legal persons’ criminal liability, which is caused by a number of reasons, first of all by the established principles of domestic criminal law doctrine.
ANTI-CORRUPTION IN POLICE BODIES OF THE RUSSIAN FEDERATION AND THE FEDERAL REPUBLIC OF GERMANY
Authors: Печегин Денис , Pechegin Denis , Прохорова Евгения , Prohorova Evgeniya
Published: September 2017

The police as a law enforcement body of a specific state was created to perform a variety of tasks in order to maintain the law and order in society, to ensure the security of the state, its citizens. In accordance with the role of the police in the legal doctrine of different countries (Germany, France, England, etc.), in due time, there were even separate schools to study this institution.
The police are also one of the subjects of anti-corruption. Nevertheless, this does not mean that corruption cannot exist in the ranks of the police. Despite the general increase in confidence in the police and their employees, noted by the All-Russia centre of studying of public opinion over the last few years in the Russian Federation, today the efforts to combat corruption need to be undertaken not only outside, but also within the police departments themselves. It is obvious that corrupt law enforcement bodies are not able to perform effectively and qualitatively their tasks, and this fast poses a real threat to the state, society and the individual. Thus, the task of improving the complex of anti-corruption measures in the police bodies is becoming more urgent.
The article presents a comparative legal analysis of anti-corruption in the police bodies of Russia and Germany in modern conditions. The measures of influence are defined, as well as the forms of interaction of law enforcement agencies in the fight against this negative social phenomenon. The authors come to conclusion that the effective system of anti-corruption in police facilitates not only by the system of legislative sanctions adopted in the state, but also by the qualitative implementation of the state’s social policy with regard to civil servants.
POTENTIAL OFF-GRID MARKETS FOR SMRS IN CANADA
Authors: Wojtaszek Daniel Tadeusz
Published: September 2017

Small modular reactors (SMRs), with <300 MWe power capacity (∼1000 MWth), are being developed to improve the safety and economics of nuclear power and to expand the application of nuclear power beyond large-scale electricity grids. A key factor to improving the economics of SMRs is the ability to capitalize on the economies associated with replication. But to capitalize on these economies, there must be a market with demands for a sufficient number of the produced SMRs. The purpose of this analysis is to estimate the market for SMRs for off-grid applications in Canada.

The potential market for SMRs in off-grid applications in Canada includes remote communities, remote mining projects, oil sands extraction and upgrading, cogeneration in a wide range of industries, and district energy systems. This study found that the potential market for off-grid SMRs in Canada consists of over 600 power plants, with a total power demand of 35 GWe. Another important finding was that most of these power plants require an installed capacity of <5 MWe.