An Economic Analysis of Global Policy Proposals to Prohibit Compensation of Blood Plasma Donors

© 2016 International Journal of the Economics of Business.Human blood plasma and its derivative therapies have been used therapeutically for more than 50 years, after first being widely used to treat injuries during World War II. In certain countries, manufacturers of these therapies – known as plasma-derived medicinal products (PDMPs) – compensate plasma donors, raising healthcare and ethical concerns among some parties. In particular, the World Health Organization has taken a strong advocacy position that compensation for blood donations should be eliminated worldwide. This review evaluates the key economic factors underlying the supply and demand for PDMPs and the evidence pointing to the policy options that are most likely to maintain a reliable supply of life-sustaining therapies. It concludes that compensated plasma donation is important for maintaining adequate and consistent supplies of plasma and limits the risk of under-treatment for the foreseeable future.

Epidemiology of diabetes and complications among adults in the Republic of Ireland 1998-2015: a systematic review and meta-analysis

Background: Accurate estimates of the burden of diabetes are essential for future planning and evaluation of services. In Ireland, there is no diabetes register and prevalence estimates vary. The aim of this review was to systematically identify and review studies reporting the prevalence of diabetes and complications among adults in Ireland between 1998 and 2015 and to examine trends in prevalence over time. Methods: A systematic literature search was carried out using PubMed and Embase. Diabetes prevalence estimates were pooled by random-effects meta-analysis. Poisson regression was carried out using data from four nationally representative studies to calculate prevalence rates of doctor diagnosed diabetes between 1998 and 2015 and was also used to assess whether the rate of doctor diagnosed diabetes changed over time. Results: Fifteen studies (eight diabetes prevalence and seven complication prevalence) were eligible for inclusion. In adults aged 18 years and over, the national prevalence of doctor diagnosed diabetes significantly increased from 2.2 % in 1998 to 5.2 % in 2015 (p trend ≤ 0.001). The prevalence of diabetes complications ranged widely depending on study population and methodology used (6.5–25.2 % retinopathy; 3.2–32.0 % neuropathy; 2.5-5.2 % nephropathy). Conclusions: Between 1998 and 2015, there was a significant increase in the prevalence of doctor diagnosed diabetes among adults in Ireland. Trends in microvascular and macrovascular complications prevalence could not be examined due to heterogeneity between studies and the limited availability of data. Reliable baseline data are needed to monitor improvements in care over time at a national level. A comprehensive national diabetes register is urgently needed in Ireland.

Trace elements in benthic foraminifera of sediment core V30-49

Eastern tropical Atlantic benthic foraminiferal Ba/Ca and Cd/Ca data from core V30-949 (3093 m) reveal large inferred changes in nutrient concentrations of deep Atlantic waters during the last 250 kyr. Relative changes in North Atlantic Deep Water contribution to this site are estimated by scaling the V30-49 Cd/Ca record to values of modern end-member water masses; these estimates agree well with the relative structure and timing of circulation changes in the eastern tropical Atlantic reconstructed from a d13C record-based mixing model (Raymo et al., 1997, doi:10.1029/97PA01019). Temporal differences between V30-49 Cd/Ca and Ba/Ca records suggest that the Ba/Ca record reflects changes in circulation with an additional increase in the Ba composition of deep Atlantic water masses during glacial episodes, possibly resulting from increased productivity. Similarity between the d13C and Ba/Ca records suggests that carbon isotopes in the deep glacial Atlantic also reflect productivity increases.

The role of acute ambient hypoxia in the regulation of myostatin

When exposed to chronic hypoxia by pathophysiological or environmental causes humans show muscle atrophy, challenging homeostasis and increasing mortality rate. Chronic hypoxia also presents with elevated myostatin peptide, a negative regulator of muscle size. This work induced acute hypoxia in healthy individuals; hypothesizing hypoxia would increase myostatin expression in both muscle and plasma in a concentration- and time-dependent manner. Hypoxia (1 % O2) reduced C2C12 myoblast migration and myotube size in vitro. Myotube atrophy was time-dependent, longer exposures showed greater atrophy. Intracellular myostatin peptide was decreased at every time point measured. Myostatin and downstream signalling pathways in muscle showed a high degree of percentage similarity between mouse and human, when amino acid sequences were directly compared. Healthy males (N = 8) were exposed to 20.9 % O2 or 11.9 % O2 for 2 hours. Following hypoxic exposure myostatin peptide was reduced in muscle but not plasma, relative to control conditions. A second cohort (N = 8) was exposed to 12.5 % O2 for 10 hours. Plasma myostatin was decreased following hypoxia, muscle myostatin trended towards increasing. A third cohort (N = 9; n = 8 lowlander, n = 1 Sherpa) was exposed to 10.7 % or 12.3 % O2 for 2 hours. Plasma myostatin was reduced at both concentrations with no difference between concentrations noted. In response to chronic hypoxia, individuals lose muscle mass. Counter to the hypothesis of an increase in myostatin in both muscle and plasma, here a consistent decrease in plasma myostatin following acute hypoxia is seen. Muscle myostatin shows a variable response, with decreasing intracellular expression seen following a 2 hour hypoxic exposure, and trends towards an increase following 10 hours of hypoxia. Decreases in plasma and muscle myostatin may represent myostatin’s movement towards peripheral compartments in these acute timeframes. Hypoxia alone is capable of altering myostatin in healthy individuals; the effects of hypoxia on myostatin appear to differ between the acute timeframes examined here and chronic exposures in environmental or disease models.

Colonialism, political unconscious and cognitive mapping in the space of the film "Captain Phillips"

The purpose of this article has been made through a Marxist analysis of the US film "Captain Phillips" (PaulGreengrass, 2013), based on a true story. I have found how the evolution of capitalism in the West continuesto consolidate the belief reified in a historical and geographical superiority of the political and socioeconomicwestern models regarding Africa and Asia lowers models. At the same time, through categories like dialecticalmaterialism, criticism of diffusionist theory and application of cognitive mapping to large geopoliticalspaces located in most poor areas of the world, I have realized a remark about currently being articulatingthe political unconscious of working class in rich countries and the poor in poor countries, establishing arelationship between the ideological representation that takes an individual from his historical reality (ona scale that moves from local to global), and how he has developed a mental ability to escape of the responsibilityto make a critical review of what's happening around him in all areas. Finally, through physicalspace captured in the film, I have realized a materialist critique of globalized business process that takesplace through the carriage of goods, outlining spatial and cognitively limits of the mentality of our time, bothamong "winners"as among the "losers", based on the spatial movement of capital.

Intraclonal heterogeneity is a critical early event in the development of myeloma and precedes the development of clinical symptoms.

The mechanisms involved in the progression from monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM) to malignant multiple myeloma (MM) and plasma cell leukemia (PCL) are poorly understood but believed to involve the sequential acquisition of genetic hits. We performed exome and whole-genome sequencing on a series of MGUS (n=4), high-risk (HR)SMM (n=4), MM (n=26) and PCL (n=2) samples, including four cases who transformed from HR-SMM to MM, to determine the genetic factors that drive progression of disease. The pattern and number of non-synonymous mutations show that the MGUS disease stage is less genetically complex than MM, and HR-SMM is similar to presenting MM. Intraclonal heterogeneity is present at all stages and using cases of HR-SMM, which transformed to MM, we show that intraclonal heterogeneity is a typical feature of the disease. At the HR-SMM stage of disease, the majority of the genetic changes necessary to give rise to MM are already present. These data suggest that clonal progression is the key feature of transformation of HR-SMM to MM and as such the invasive clinically predominant clone typical of MM is already present at the SMM stage and would be amenable to therapeutic intervention at that stage.

MMSET deregulation affects cell cycle progression and adhesion regulons in t(4;14) myeloma plasma cells

BackgroundThe recurrent immunoglobulin translocation, t(4;14)(p16;q32) occurs in 15% of multiple myeloma patients and is associated with poor prognosis, through an unknown mechanism. The t(4;14) up-regulates fibroblast growth factor receptor 3 (FGFR3) and multiple myeloma SET domain (MMSET) genes. The involvement of MMSET in the pathogenesis of t(4;14) multiple myeloma and the mechanism or genes deregulated by MMSET upregulation are still unclear.Design and MethodsThe expression of MMSET was analyzed using a novel antibody. The involvement of MMSET in t(4;14) myelomagenesis was assessed by small interfering RNA mediated knockdown combined with several biological assays. In addition, the differential gene expression of MMSET-induced knockdown was analyzed with expression microarrays. MMSET gene targets in primary patient material was analyzed by expression microarrays.ResultsWe found that MMSET isoforms are expressed in multiple myeloma cell lines, being exclusively up-regulated in t(4;14)-positive cells. Suppression of MMSET expression affected cell proliferation by both decreasing cell viability and cell cycle progression of cells with the t(4;14) translocation. These findings were associated with reduced expression of genes involved in the regulation of cell cycle progression (e.g. CCND2, CCNG1, BRCA1, AURKA and CHEK1), apoptosis (CASP1, CASP4 and FOXO3A) and cell adhesion (ADAM9 and DSG2). Furthermore, we identified genes involved in the latter processes that were differentially expressed in t(4;14) multiple myeloma patient samples.ConclusionsIn conclusion, dysregulation of MMSET affects the expression of several genes involved in the regulation of cell cycle progression, cell adhesion and survival.

Demonstration of passive plasma lensing of a laser wakefield accelerated electron bunch

We report on the first demonstration of passive all-optical plasma lensing using a two-stage setup. An intense femtosecond laser accelerates electrons in a laser wakefield accelerator (LWFA) to 100 MeVover millimeter length scales. By adding a second gas target behind the initial LWFAstage we introduce a robust and independently tunable plasma lens. We observe a density dependent reduction of the LWFA electron beam divergence from an initial value of 2.3 mrad, down to 1.4 mrad (rms), when the plasma lens is in operation. Such a plasma lens provides a simple and compact approach for divergence reduction well matched to the mm-scale length of the LWFA accelerator. The focusing forces are provided solely by the plasma and driven by the bunch itself only, making this a highly useful and conceptually new approach to electron beam focusing. Possible applications of this lens are not limited to laser plasma accelerators. Since no active driver is needed the passive plasma lens is also suited for high repetition rate focusing of electron bunches. Its understanding is also required for modeling the evolution of the driving particle bunch in particle driven wake field acceleration.

Nitriding in cathodic cage of stainless steel AISI 316: influence of sample position

R.R.M. de Sousa et al. Nitriding in cathodic cage of stainless steel AISI 316: Influence of sample position. Vacuum, [s.l.], n.83, 2009. Disponivel em: plasma.ct.ufrn.br/index.php?id=5>. Acesso em: 04 out.2010.

Dimethyl Acetals, an Indirect Marker of the Endogenous Antioxidant Plasmalogen Level, are Reduced in Blood Lipids of Sudanese Pre-eclamptic Subjects whose Background Diet is High in Carbohydrate

In Sudanese women with (n = 60) and without (n = 65) pre-eclampsia, circulating lipids, plasma and red cell saturated and monounsaturated fatty (MUFA) acids and dimethyl acetals (DMAs) were investigated. DMAs are an indirect marker of levels of plasmalogens, endogenous antioxidants, which play a critical role in oxidative protection, and cholesterol homeostasis. The pre-eclamptics had higher C18:1n-9 (p < 0.001) and ΣMUFA (p < 0.01) in plasma free fatty acids, C16:1n-7, C18:1n-9, ΣMUFA; 16:0/16:1n-7 (p < 0.01) in erythrocyte choline phosphoglycerides (ePC) and 16:1n-7, 18:1n-7 and 16:0/16:1n-7 (p < 0.01) in erythrocyte ethanolamine phosphoglycerides (ePE). In contrast, the DMAs 18:0, 18:1 and ΣDMAs in ePE, and 16:0, 18:0 and ΣDMAs in ePC were reduced (p < 0.001) in the pre-eclamptic women. This study of pregnant women with high carbohydrate and low fat background diet suggests pre-eclampsia is associated with oxidative stress and enhanced activity of the microsomal enzyme stearyl-CoA desaturase (delta 9 desaturase), as assessed by palmitic/palmitoleic (C16:0/C16:n-1) and stearic/oleic (C18/C18:1n-9) ratios.

Nitriding in cathodic cage of stainless steel AISI 316: influence of sample position

R.R.M. de Sousa et al. Nitriding in cathodic cage of stainless steel AISI 316: Influence of sample position. Vacuum, [s.l.], n.83, 2009. Disponivel em: plasma.ct.ufrn.br/index.php?id=5>. Acesso em: 04 out.2010.

Hyperprolinemia as a clue in the diagnosis of a patient with a psychiatric disorder

Background: Over the last few years, microdeletions of the 22q11.2 region responsible for DiGeorge syndrome, or velocardiofacial syndrome, have been increasingly related to neuropsychiatric disorders including schizophrenia and bipolar disorders. These signs seem to be related to certain genes located in the hemideleted region as the proline dehydrogenase (PRODH) and the catecholo-methyltransferase (COMT) genes. The PRODH or proline oxidase deficiency is responsible for hyperprolinemia type 1 (HPI) also causing psychiatric manifestations. Case Report: We describe a 17 year old boy with previous mild psychomotor and speech delay, mild cognitive impairment, and obsessive behaviours who started his adolescent psychiatric care presenting irritablemood and aggressive behaviour with schizophrenia symptoms that scored a “severely ill” level PANSS assessment. Symptoms got worse when he was treated with valproic acid and plasma aminoacids showing increase in alanine and proline, suggested a mitochondrial involvement of the proline metabolic pathway. Results: Mild dysmorphia suggested a possible 22q11.2 deletion genetically confirmed involving both the PRODH and COMT regions. HPI that can present with psychiatric features is however a recessive disorder and therefore the symptoms could not be solely explained by this genetic deletion. Additional investigations also showed disclosed a p.L289m (c.1865 T > A) mutation in the PRODH gene. Discussion: We believe that the association of this mutation together with the 22q11.2 deletion would lead to a decrease of functional protein. Although it may be difficult to diagnosis chromosomal abnormalities in patients with no clear malformations and mild dysmorphic features as in this patient we emphasize need to investigate the aetiology in patients with psychiatric symptoms, especially if they have other systemic manifestations such as developmental delay or psychotic symptoms, as it may be important in the management of the patients.