The Retail FX Trader: Random Trading and the Negative Sum Game

With the internet boom of early 2000 making access to trading the Foreign Exchange (FX) market far simpler for members of the general public, the growth of 'retail' FX trading continues, with daily transaction volumes as high as $200 billion. Potential new entrants to the retail FX trading world may come from the recent UK pension deregulations, further increasing the volumes. The attraction of FX trading is that it offers high returns and whilst it has been understood that it is high-risk in nature, the rewards are seen as being commensurately high for the 'skilled and knowledgeable' trader who has an edge over other market participants. This paper analyses a number of independent sources of data and previous research, to examine the profitability of the Retail FX trader and compares the results with that of a simulated random trading models. This paper finds evidence to suggest that whilst approximately 20% of traders can expect to end up with a profitable account, around 40% might expect their account to be subject to a margin call. This paper finds a strong correlation between the overall profitability of traders and impact of the cost of the bid-ask spread, whilst finding little if any evidence that retail FX traders, when viewed as a group, are achieving results better than that from random trading

Alpha B-crystallin protects retinal tissue during Staphylococcus aureus-induced endophthalmitis

Bacterial infections of the eye highlight a dilemma that is central to all immune-privileged sites. On the one hand, immune privilege limits inflammation to prevent bystander destruction of normal tissue and loss of vision. On the other hand, bacterial infections require a robust inflammatory response for rapid clearance of the pathogen. We demonstrate that the retina handles this dilemma, in part, by activation of a protective heat shock protein. During Staphylococcus aureus-induced endophthalmitis, the small heat shock protein αB-crystallin is upregulated in the retina and prevents apoptosis during immune clearance of the bacteria. In the absence of αB-crystallin, mice display increased retinal apoptosis and retinal damage. We found that S. aureus produces a protease capable of cleaving αB-crystallin to a form that coincides with increased retinal apoptosis and tissue destruction. We conclude that αB-crystallin is important in protecting sensitive retinal tissue during destructive inflammation that occurs during bacterial endophthalmitis

Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromosome 21q21.3 and identified bi-allelic variants in JAM2. JAM2 encodes for the junctional-adhesion-molecule-2, a key tight-junction protein in blood-brain-barrier permeability. We show that JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient's fibroblasts, consistent with a loss-of-function mechanism. We show that the human phenotype is replicated in the jam2 complete knockout mouse (jam2 KO). Furthermore, neuropathology of jam2 KO mouse showed prominent vacuolation in the cerebral cortex, thalamus, and cerebellum and particularly widespread vacuolation in the midbrain with reactive astrogliosis and neuronal density reduction. The regions of the human brain affected on neuroimaging are similar to the affected brain areas in the myorg PFBC null mouse. Along with JAM3 and OCLN, JAM2 is the third tight-junction gene in which bi-allelic variants are associated with brain calcification, suggesting that defective cell-to-cell adhesion and dysfunction of the movement of solutes through the paracellular spaces in the neurovascular unit is a key mechanism in CNS calcification

The Functional DRD3 Ser9Gly Polymorphism (rs6280) Is Pleiotropic, Affecting Reward as Well as Movement

Abnormalities of motivation and behavior in the context of reward are a fundamental component of addiction and mood disorders. Here we test the effect of a functional missense mutation in the dopamine 3 receptor (DRD3) gene (ser9gly, rs6280) on reward-associated dopamine (DA) release in the striatum. Twenty-six healthy controls (HCs) and 10 unmedicated subjects with major depressive disorder (MDD) completed two positron emission tomography (PET) scans with [11C]raclopride using the bolus plus constant infusion method. On one occasion subjects completed a sensorimotor task (control condition) and on another occasion subjects completed a gambling task (reward condition). A linear regression analysis controlling for age, sex, diagnosis, and self-reported anhedonia indicated that during receipt of unpredictable monetary reward the glycine allele was associated with a greater reduction in D2/3 receptor binding (i.e., increased reward-related DA release) in the middle (anterior) caudate (p<0.01) and the ventral striatum (p<0.05). The possible functional effect of the ser9gly polymorphism on DA release is consistent with previous work demonstrating that the glycine allele yields D3 autoreceptors that have a higher affinity for DA and display more robust intracellular signaling. Preclinical evidence indicates that chronic stress and aversive stimulation induce activation of the DA system, raising the possibility that the glycine allele, by virtue of its facilitatory effect on striatal DA release, increases susceptibility to hyperdopaminergic responses that have previously been associated with stress, addiction, and psychosis

Getting the message straight: effects of a brief hepatitis prevention intervention among injection drug users

To redress gaps in injection drug users' (IDUs) knowledge about hepatitis risk and prevention, we developed a brief intervention to be delivered to IDUs at syringe exchange programs (SEPs) in three US cities. Following a month-long campaign in which intervention packets containing novel injection hygiene supplies and written materials were distributed to every client at each visit, intervention effectiveness was evaluated by comparing exposed and unexposed participants' self-reported injection practices. Over one-quarter of the exposed group began using the novel hygiene supplies which included an absorbent pad ("Safety Square") to stanch blood flow post-injection. Compared to those unexposed to the intervention, a smaller but still substantial number of exposed participants continued to inappropriately use alcohol pads post-injection despite exposure to written messages to the contrary (22.8% vs. 30.0%). It should also be noted that for those exposed to the intervention, 8% may have misused Safety Squares as part of pre-injection preparation of their injection site; attention should be paid to providing explicit and accurate instruction on the use of any health promotion materials being distributed. While this study indicates that passive introduction of risk reduction materials in injection drug users through syringe exchange programs can be an economical and relatively simple method of changing behaviors, discussions with SEP clients regarding explicit instructions about injection hygiene and appropriate use of novel risk reduction materials is also needed in order to optimize the potential for adoption of health promotion behaviors. The study results suggest that SEP staff should provide their clients with brief, frequent verbal reminders about the appropriate use when distributing risk reduction materials. Issues related to format and language of written materials are discussed

Biallelic mutations in neurofascin cause neurodevelopmental impairment and peripheral demyelination.

Axon pathfinding and synapse formation are essential processes for nervous system development and function. The assembly of myelinated fibres and nodes of Ranvier is mediated by a number of cell adhesion molecules of the immunoglobulin superfamily including neurofascin, encoded by the NFASC gene, and its alternative isoforms Nfasc186 and Nfasc140 (located in the axonal membrane at the node of Ranvier) and Nfasc155 (a glial component of the paranodal axoglial junction). We identified 10 individuals from six unrelated families, exhibiting a neurodevelopmental disorder characterized with a spectrum of central (intellectual disability, developmental delay, motor impairment, speech difficulties) and peripheral (early onset demyelinating neuropathy) neurological involvement, who were found by exome or genome sequencing to carry one frameshift and four different homozygous non-synonymous variants in NFASC. Expression studies using immunostaining-based techniques identified absent expression of the Nfasc155 isoform as a consequence of the frameshift variant and a significant reduction of expression was also observed in association with two non-synonymous variants affecting the fibronectin type III domain. Cell aggregation studies revealed a severely impaired Nfasc155-CNTN1/CASPR1 complex interaction as a result of the identified variants. Immunofluorescence staining of myelinated fibres from two affected individuals showed a severe loss of myelinated fibres and abnormalities in the paranodal junction morphology. Our results establish that recessive variants affecting the Nfasc155 isoform can affect the formation of paranodal axoglial junctions at the nodes of Ranvier. The genetic disease caused by biallelic NFASC variants includes neurodevelopmental impairment and a spectrum of central and peripheral demyelination as part of its core clinical phenotype. Our findings support possible overlapping molecular mechanisms of paranodal damage at peripheral nerves in both the immune-mediated and the genetic disease, but the observation of prominent central neurological involvement in NFASC biallelic variant carriers highlights the importance of this gene in human brain development and function

Influence of sense of coherence on adolescents' self-perceived dental aesthetics:a cross-sectional study

Background Sense of coherence (SOC) is a psychosocial factor capable of influencing perception of health, improving one’s ability to manage life. It is the central construct of salutogenesis. SOC allows for identification and mobilization of resources to effectively manage or solve problems, promoting health and quality of life. Using Wilson-Cleary’s conceptual model we hypothesized that SOC might contribute to self-perception of dental aesthetics. The aim of this study was to investigate whether SOC levels were related to self-perception of dental aesthetics against assessed normative orthodontic treatment need among adolescents. Methods A cross-sectional study was conducted with 615 male and female adolescents aged 12 to 15 years. Data collection comprised socio-demographic and socio-economic characteristics, SOC (SOC 13), self-perceived dental aesthetics (Oral Aesthetic Subjective Impact Scale), and assessment of orthodontic treatment need (Dental Aesthetic Index). Statistical analysis involved Pearson’s chi-square test, Kruskal-Wallis test, Mann-Whitney test and multiple linear regression. Spearman’s correlation coefficient was calculated for the determination of the strength of correlations among the numerical variables. The level of significance was set at 5% (p < 0.05). Results 50.1% of the participants were classified as having a high SOC (≥ median). Overall, SOC was associated with self-perceived dental aesthetics (p = 0.048). In the adolescents with no orthodontic treatment need, those with a low SOC perceived their dental aesthetics more negatively than those with high levels of SOC. The multiple regression analysis demonstrated an inverse relationship between SOC and: 1) age (p = 0.007), SOC being higher in the younger age group; 2) self-perceived dental aesthetics (p = 0.001), a higher SOC being associated with those who had a positive dental self-perception. Conclusions SOC was associated with self-perceived dental aesthetics and adolescents with a high SOC were more likely to perceive their dental aesthetics more positively. SOC did not seem to influence self-perception of dental aesthetics in adolescents who were clinically assessed as having an orthodontic treatment need, however, in those where there was no orthodontic treatment need, a low SOC was associated with a negative self-perception of dental appearance

A Scoping Review of Home Produced Heroin and Amphetamine Type Stimulant Substitutes: Implications for Prevention, Treatment and Policy

Several home-produced substances such as krokodil and boltushka are prevalent in many Eastern European countries. Anecdotal reports of its use have been circulating in Germany and Norway; however, this has not been confirmed. Its use has also been reported by the media in the USA, although only one confirmed report of its use exists. Home-produced drugs are associated with high levels of morbidity and a number of complex health issues such as the spread of blood borne viruses, gangrene, and internal organ damage. The high incidence of HIV rates amongst people who inject home-produced substances is a public health concern. The resulting physical health consequences of injecting these crude substances are very severe in comparison to heroin or amphetamine acquired in black markets. Due to this fact and the increased mortality associated with these substances, professionals in the area of prevention, treatment, and policy development need to be cognisant of the presentation, harms, and the dangers associated with home-produced substances globally. This scoping review aimed to examine existing literature on the subject of home-produced heroin and amphetamine-type stimulant substitutes. The review discussed the many implications such research may have in the areas of policy and practice. Data were gathered through the use of qualitative secondary resources such as journal articles, reports, reviews, case studies, and media reports. The home production of these substances relies on the utilisation of precursor drugs such as less potent stimulants, tranquillizers, analgesics, and sedatives or natural plant ingredients. The Internet underpins the facilitation of this practice as recipes, and diverted pharmaceutical sales are available widely online, and currently, ease of access to the Internet is evident worldwide. This review highlights the necessity of prevention, education, and also harm reduction related to home-produced drugs and also recommends consistent monitoring of online drug fora, online drug marketplaces, and unregulated pharmacies

Is cardiopulmonary transit time (CPTT) measured by using dynamic rubidium cardiac PET/CT a predictor for cardiac function?

Cardiopulmonary transit time (CPTT) represents the time needed for the circulation of blood from the right to the left ventricle. This parameter can be measured during dynamic acquisition of rubidium ([$^{82}$Rb]) cardiac PET/CT. To further characterize this marker, we wanted to assess the association between CPTT and parameters of cardiac function derived from echocardiography. Retrospective single center analysis of patients referred to [$^{82}$Rb]RbCl-PET/CT with rest/stress protocol on an integrated hybrid PET/CT system (Biograph mCT, Siemens Healthineers, Erlangen, Germany) and echocardiography within 100 days. After intravenous injection of 7.5 MBq/kg [$^{82}$Rb]RbCl dynamic scans with initially 12 × 10 s frames were started. For data analysis a volume of interest (VOI) was drawn in the left and right ventricle using dedicated software. The difference between the peak time for the two time activity curves (TAC) was extracted as CPTT and normalized for heart rate (NCPTT). Associations between NCPTT and echo parameters such as left ventricular ejection fraction (EF$_{Echo}$) were analyzed using linear regression models. 44 patients (sex: 28 male, 16 female) were enrolled with a time difference between PET and echocardiography of 19.65 ± 23.3 days. 9 patients had a rest CPTT of 0 s, 32 patients 10 s and 3 patients 20 s. The association between EF$_{Echo}$ and NCPTT revealed a significant negative correlation (beta = -0.77; CI: -1.32, -0.22; p = 0.007). Given this association, univariate predictive models for EF$_{Echo}$ were applied. Root mean square error was 6.83% for the EF$_{PET}$, and 6.0% for NCPTT, which indicates a slightly higher predictive performance for the NCPTT model with a lower error. Pulmonary transit time can be estimated with [$^{82}$Rb]RbCl-PET/CT, with a high positive association to rest EF$_{Echo}$. However, smaller time frames than 10 s are needed, for more accurate estimation of cardiac function