Maintained hand function and forearm bone health 14 months after an in-home virtual-reality videogame hand telerehabilitation intervention in an adolescent with hemiplegic cerebral palsy

Virtual reality videogames can be used to motivate rehabilitation, and telerehabilitation can be used to improve access to rehabilitation. These uses of technology to improve health outcomes are a burgeoning area of rehabilitation research. So far, there is a lack of reports of long-term outcomes of these types of interventions. The authors report a 15-year-old boy with hemiplegic cerebral palsy and epilepsy because of presumed perinatal stroke who improved his plegic hand function and increased his plegic forearm bone health during a 14-month virtual reality videogame hand telerehabilitation intervention. A total of 14 months after the intervention ended, repeat evaluation demonstrated maintenance of both increased hand function and forearm bone health. The implications of this work for the future of rehabilitation in children with neurological disabilities are discussed in this article

Transcriptome-pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS.

Sporadic amyotrophic lateral sclerosis (sALS) is the most common form of ALS, however, the molecular mechanisms underlying cellular damage and motor neuron degeneration remain elusive. To identify molecular signatures of sALS we performed genome-wide expression profiling in laser capture microdissection-enriched surviving motor neurons (MNs) from lumbar spinal cords of sALS patients with rostral onset and caudal progression. After correcting for immunological background, we discover a highly specific gene expression signature for sALS that is associated with phosphorylated TDP-43 (pTDP-43) pathology. Transcriptome-pathology correlation identified casein kinase 1ε (CSNK1E) mRNA as tightly correlated to levels of pTDP-43 in sALS patients. Enhanced crosslinking and immunoprecipitation in human sALS patient- and healthy control-derived frontal cortex, revealed that TDP-43 binds directly to and regulates the expression of CSNK1E mRNA. Additionally, we were able to show that pTDP-43 itself binds RNA. CK1E, the protein product of CSNK1E, in turn interacts with TDP-43 and promotes cytoplasmic accumulation of pTDP-43 in human stem-cell-derived MNs. Pathological TDP-43 phosphorylation is therefore, reciprocally regulated by CK1E activity and TDP-43 RNA binding. Our framework of transcriptome-pathology correlations identifies candidate genes with relevance to novel mechanisms of neurodegeneration

Shared genetic variants suggest common pathways in allergy and autoimmune diseases.

BACKGROUND: The relationship between allergy and autoimmune disorders is complex and poorly understood. OBJECTIVE: To investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms. METHODS: We meta-analyzed two GWAS on self-reported allergy and sensitization comprising a total of 62,330 individuals. These results were used to calculate enrichment for SNPs previously associated with autoimmune diseases. Furthermore, we probed for enrichment within genetic pathways and of transcription factor binding sites, and characterized commonalities in the variant burden on tissue-specific regulatory sites by calculating the enrichment of allergy SNPs falling in gene regulatory regions in various cells using Encode Roadmap DHS data, and compared the allergy data with all known diseases. RESULTS: Among 290 loci previously associated with 16 autoimmune diseases, we found a significant enrichment of loci also associated with allergy (p=1.4e-17) encompassing 29 loci at a false discovery rate<0.05. Such enrichment seemed to be a general characteristic for all autoimmune diseases. Among the common loci, 48% had the same direction of effect for allergy and autoimmune diseases. Additionally, we observed an enrichment of allergy SNPs falling within immune pathways and regions of chromatin accessible in immune cells that was also represented in autoimmune diseases, but not in other diseases. CONCLUSION: We identified shared susceptibility loci and commonalities in pathways between allergy and autoimmune diseases, suggesting shared diseases mechanisms. Further studies of these shared genetic mechanisms might help understanding the complex relationship between these diseases, including the parallel increase in disease prevalence

A pragmatic randomised controlled trial of the Welsh National Exercise Referral Scheme: protocol for trial and integrated economic and process evaluation

Background: The benefits to health of a physically active lifestyle are well established and there is evidence that a sedentary lifestyle plays a significant role in the onset and progression of chronic disease. Despite a recognised need for effective public health interventions encouraging sedentary people with a medical condition to become more active, there are few rigorous evaluations of their effectiveness. Following NICE guidance, the Welsh national exercise referral scheme was implemented within the context of a pragmatic randomised controlled trial. Methods/Design: The randomised controlled trial, with nested economic and process evaluations, recruited 2,104 inactive men and women aged 16+ with coronary heart disease (CHD) risk factors and/or mild to moderate depression, anxiety or stress. Participants were recruited from 12 local health boards in Wales and referred directly by health professionals working in a range of health care settings. Consenting participants were randomised to either a 16 week tailored exercise programme run by qualified exercise professionals at community sports centres (intervention), or received an information booklet on physical activity (control). A range of validated measures assessing physical activity, mental health, psycho-social processes and health economics were administered at 6 and 12 months, with the primary 12 month outcome measure being 7 day Physical Activity Recall. The process evaluation explored factors determining the effectiveness or otherwise of the scheme, whilst the economic evaluation determined the relative cost-effectiveness of the scheme in terms of public spending. Discussion: Evaluation of such a large scale national public health intervention presents methodological challenges in terms of trial design and implementation. This study was facilitated by early collaboration with social research and policy colleagues to develop a rigorous design which included an innovative approach to patient referral and trial recruitment, a comprehensive process evaluation examining intervention delivery and an integrated economic evaluation. This will allow a unique insight into the feasibility, effectiveness and cost effectiveness of a national exercise referral scheme for participants with CHD risk factors or mild to moderate anxiety, depression, or stress and provides a potential model for future policy evaluations. Trial registration: Current Controlled Trials ISRCTN4768044

Earnings management in South Africa: evidence and implications

Doctoral thesis submitted to the University of the Witwatersrand, Faculty of Commerce, Law and Management in fulfilment of the requirements for the degree of the Doctor in Philosophy, December 2016Healy and Wahlen (1999:368) define earnings management as an event that “occurs when managers use judgement in financial reporting and in structuring transactions to alter financial reports to either mislead some stakeholders about the underlying economic performance of the company or to influence contractual outcomes that depend on reported accounting numbers.” Management’s intent to mislead users distinguishes accruals that signal managers’ inside information about future cash flows from earnings management which intends to misrepresent performance (Dechow and Skinner, 2000; Parfet, 2000). Earnings management is a very serious issue; if it is not detected it can result in large financial losses for investors and creditors. Earnings data is a fundamental input to valuing a firm’s shares and prospects. Erroneous assessments of future cash flows because of misleading information will result in invalid share valuations and incorrect lending decisions which can have negative consequences on capital markets. The severe negative consequences of earnings manipulation, if undetected, suggest that investors, auditors and regulatory bodies should be aware of the prevalence of earnings management in an economy, whether investors are able to detect and price suspected earnings management and the most efficient way to detect it. This thesis aims to answer two fundamental questions: Does earnings management exist in South Africa? Are investors in South Africa misled by earnings management? How to detect earnings manipulation is the predominant theme in earnings management literature. The majority of research has been conducted in advanced economies and has transformed from identifying discontinuities in earnings distributions and measuring discretionary accruals to sophisticated predictive models, such as the F-score (Dechow, Ge, Larson and Sloan, 2011). Yet, research into the subject is sparse in emerging markets and tends to replicate existing methodology. The objective of this thesis is to examine earnings management in the South African economy, with the specific aim of identifying a databank of suspected earnings management firms that can be used for further research. Because the number of firms that have been forced to restate earnings is small in this environment, this thesis resorts to identifying suspected earnings management firms using discontinuities in earnings distributions. South Africa is similar to other emerging economies in that it is characterised by concentrated ownership, weaker legal enforcement and a smaller stock exchange. The South African environment is dissimilar to emerging economies as the JSE is considered to be well regulated, accounting and auditing standards are world class and accounting transparency and disclosure are satisfactory (Leuz, Nanda, and Wysocki, 2003). The results of this thesis are relevant in an institutional and macroeconomic setting where incentives to manipulate earnings, enforcement, legal protection, rule of law and sample size may differ from those in developed economies. This thesis firstly, focuses on methodological issues that may be encountered by researchers in identifying discontinuities in earnings distributions in emerging economies and secondly, validates kernel density estimation, Lahr (2014), as a viable methodology to test for earnings management by comparing total accruals, discretionary accruals and working capital accruals between suspected earnings management and non-earnings management firms. Thirdly, deferred tax expense is considered as a predictor variable in place of discretionary accruals in detecting suspected earnings management firms. Finally, in order to investigate investors’ reaction to suspected earnings management this thesis investigates whether the market prices suspected earnings management firms differently from non-earnings management firms. Pre- selected researcher binwidths (Burgstahler and Dichev, 1997, Coulton, Taylor and Taylor, 2005, Glaum, Lichtblau, and Lindemann, 2004; Holland and Ramsay, 2003) prove to be unsuitable in this milieu. Consequently kernel density estimation Lahr (2014), which derives bandwidths from the empirical earnings distributions, is used to identify discontinuities and to concurrently investigate the effect of deflation on the location of discontinuities. Discontinuities are shown to exist in earnings levels and changes distributions and emerge around zero in earnings levels distributions where number of shares is the deflator. Two important results emerge from this analysis. Firstly, when kernel density estimation is used in levels distributions, there is evidence that deflating by market value of equity and total assets shifts the location of suspected earnings management firms to the second and third intervals to the right of zero. Scaling does not alter the location of suspected earnings management firms in earnings changes distributions. Secondly, in the earnings deflated by number of shares distribution there is evidence that the band of suspected earnings management firms contains the results of firms that have upwardly and downwardly manipulated earnings. The implication of these findings are that deflating by number of shares is probably the most efficient scalar and that if doubt exists, alternative deflators should, at least, be compared between profit and loss firms. In addition, in the presence of evidence of downwards earnings management, researchers should evaluate whether and how to identify firms that are suspected of having reduced earnings. Specifically in emerging market research, these results indicate that it is inappropriate to merely replicate distribution research based on researcher selected binwidths and that kernel density estimation is probably more efficient in identifying discontinuities as it gives researchers a much broader perspective on the location of discontinuities. Kernel density estimation is confirmed as a method to identify discontinuities in earnings levels and changes distributions by comparing total, discretionary and working capital accruals between suspected earnings management and non-earnings management firms. Evidence that discontinuities in earnings distributions may be attributable to earnings management activities is found where earnings levels and earnings changes are deflated by number of shares and market value of equity, both modified Jones and asymmetric BS discretionary accruals are significantly income increasing in suspected earnings management (EM) firms and income decreasing in non-EM firms. Scaling by total assets is not a suitable deflator in the South African context as it appears to affect the sign and statistical significance of the accruals metrics in the earnings levels before and after tax distributions. This result does not detract from the efficiency of kernel density estimation as it is attributable to the inefficiency of total accruals as a scalar in an emerging market environment. Furthermore, this research endorses Ball and Shivakumar’s (2006) (BS) finding that an asymmetric discretionary accruals model is more efficient in estimating discretionary accruals in all the distributions, irrespective of deflators. In addition, the results of this thesis show that, in an emerging economy, deferred tax is incrementally useful to modified- Jones and the asymmetric BS discretionary accruals in detecting earnings management. The implication of this result is useful to investors, auditors and regulators because deferred tax movements and its components are a visible and identifiable numbers in financial statements. Deferred tax expense can be used, instead of complicated discretionary accrual models, to identify evidence of earnings management. This means that the components of the deferred tax asset or liability accounts can be analysed to highlight unusual movements which may in turn, focus attention on unusual accruals. For researchers, this result has important implications. Kernel density estimation can be used to identify suspected earnings management firms which can be used to further research. The final chapter of this thesis explores whether investors price suspected earnings management and nonearnings management firms differently and finds that, in this South African sample, there is no difference in price levels or cumulative abnormal returns in suspected earnings management and non-earnings management firms. This result is in sharp contrast to Balsam, Bartov, and Marquardt (2002) and Baber, Shuping, and Sok-Hyong (2006) who report a negative association between unexpected discretionary accruals and cumulative abnormal returns and Keung, Lin, and Shih (2010) who find that investors react negatively to zero or small earnings surprises. To some extent the results of this section of the thesis supports the finding in Gavious (2007) that prices react to discretionary accruals only after the introduction of revised analysts’ forecasts.The finding in this thesis implies that investors in South Africa are unable to detect earnings management. This outcome should be viewed in the context of prior research that reports that the JSE may be inefficient (Bhana, 1995, 2005, 2010; Hoffman, 2012; Ward and Muller, 2012; Watson and Roussow, 2012) and may be attributed to the fact that there is no signal to investors that the quality of earnings may be questionable in the sample of suspected earnings management firms. All in all, the findings of this thesis indicate the existence of earnings management in listed companies in South Africa.XL201

Emergency department throughput, crowding, and financial outcomes for hospitals

Emergency department (ED) crowding has been identified as a major public health problem in the United States by the Institute of Medicine. ED crowding not only is associated with poorer patient outcomes, but it also contributes to lost demand for ED services when patients leave without being seen and hospitals must go on ambulance diversion. However, somewhat paradoxically, ED crowding may financially benefit hospitals. This is because ED crowding allows hospitals to maximize occupancy with well-insured, elective patients while patients wait in the ED. In this article, the authors propose a more holistic model of hospital flow and revenue that contradicts this notion and offer suggestions for improvements in ED and hospital management that may not only reduce crowding and improve quality, but also increase hospital revenues. Also proposed is that increased efficiency and quality in U.S. hospitals will require changes in systematic microeconomic and macroeconomic incentives that drive the delivery of health services in the United States. Finally, the authors address several questions to propose mutually beneficial solutions to ED crowding that include the realignment of hospital incentives, changing culture to promote flow, and several ED-based strategies to improve ED efficiency