Facets of Parenting a Child with Hypoplastic Left Heart Syndrome

The purpose of the study was to conceptualize the needs of parents of young children with hypoplastic left heart syndrome (HLHS) to provide a theoretical framework to inform the development of future parent interventions. Participants were parents and grandparents (n = 53) of 15 young children who had undergone the Sano surgical approach for HLHS. Analysis of recorded and transcribed single interviews with each participant was done as directed by interpretive description methodology. A model of five facets of parenting was conceptualized. These included survival parenting, “hands-off” parenting, expert parenting, uncertain parenting, and supported parenting. The facets of parenting delineated through this study provide a theoretical framework that can be used to guide the development and evaluation of interventions for parents of children with complex congenital heart disease and potentially other life-threatening conditions. Each facet constitutes a critical component for educational or psychosocial intervention for parents

On-stack replacement, distilled

On-stack replacement (OSR) is essential technology for adaptive optimization, allowing changes to code actively executing in a managed runtime. The engineering aspects of OSR are well-known among VM architects, with several implementations available to date. However, OSR is yet to be explored as a general means to transfer execution between related program versions, which can pave the road to unprecedented applications that stretch beyond VMs. We aim at filling this gap with a constructive and provably correct OSR framework, allowing a class of general-purpose transformation functions to yield a special-purpose replacement. We describe and evaluate an implementation of our technique in LLVM. As a novel application of OSR, we present a feasibility study on debugging of optimized code, showing how our techniques can be used to fix variables holding incorrect values at breakpoints due to optimizations

"Well the Future, that is Difficult": a hermeneutic phenomenological analysis exploring the maternal experience of parenting a young adult with a developmental disability

- Background: The predominant focus of extant literature exploring maternal experience of developmental disability has been stress, adaptation, efficacy of interventions and the burden of care. Most studies involve mothers of children, with scant attention given to what life is like later. This study qualitatively explores the experience of mothers of young adults (aged 19–28). - Materials and methods: Semi-structured interviews conducted with six women aged 48–60 were transcribed and analysed using interpretative phenomenological analysis. - Results: Three themes illustrate how mothers are confronted with their adult children's continuing need for support and how a lack of trust in social care creates anxiety about the future, increasing awareness of mortality. - Conclusions: Vulnerability represents a useful concept for understanding these findings theoretically. Galvin & Todres’ (2013) conceptual framework for the humanization of care provides the opportunity to prioritize the needs of individuals by highlighting dimensions of existence which confer meaning

Confirmation that somatic mutations of beta-2 microglobulin correlate with a lack of recurrence in a subset of stage II mismatch repair deficient colorectal cancers from the QUASAR trial

Aims: Beta2‐Microglobulin (B2M) forms part of the HLA class I complex and plays a role in metastatic biology. B2M mutations occur frequently in mismatch repair‐deficient colorectal cancer (dMMR CRC) with limited data suggesting they may protect against recurrence. Our experimental study tested this hypothesis by investigating B2M mutation status and B2M protein expression and recurrence in patients in the stage II QUASAR clinical trial. Methods: Sanger sequencing was performed for the three coding exons of B2M on 121 dMMR and a subsample of 108 pMMR tumours; 52 with recurrence and 56 without. B2M protein expression was assessed by immunohistochemistry. Mutation status and protein expression were correlated with recurrence and compared to proficient mismatch repair (pMMR) CRCs. Results: Deleterious B2M mutations were detected in 39/121 (32%) dMMR tumours. Five contained missense B2M‐variants of unknown significance, so were excluded from further analyses. With median follow‐up 7.4 years, none of the 39 B2M‐mutant tumours recurred, compared with 14/77 (18%) B2M‐wildtype tumours (p=0.005); six at local and eight at distant sites. Sensitivity and specificity of IHC in detecting B2M mutations was 87% and 71% respectively. Significantly (p<0.0001) fewer 3/104 (2.9%) of the 108 pMMR CRCs demonstrated deleterious B2M mutations. One pMMR tumour, containing a frameshift mutation, later recurred. Conclusion: B2M mutations were detected in nearly one third of dMMR cancers, none of which recurred. B2M mutation status has potential clinical utility as a prognostic biomarker in stage II dMMR CRC. The mechanism of protection against recurrence and whether this protection extends to stage III disease remains unclear

Neuroactive steroids in depression and anxiety disorders: Clinical studies

Certain neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially 3 alpha-reduced pregnane steroids are potent positive allosteric modulators of the gamma-aminobutyric acid type A (GABA(A)) receptor. During major depression, there is a disequilibrium of 3 alpha-reduced neuroactive steroids, which is corrected by clinically effective pharmacological treatment. To investigate whether these alterations are a general principle of successful antidepressant treatment, we studied the impact of nonpharmacological treatment options on neuroactive steroid concentrations during major depression. Neither partial sleep deprivation, transcranial magnetic stimulation, nor electroconvulsive therapy affected neuroactive steroid levels irrespectively of the response to these treatments. These studies suggest that the changes in neuroactive steroid concentrations observed after antidepressant pharmacotherapy more likely reflect distinct pharmacological properties of antidepressants rather than the clinical response. In patients with panic disorder, changes in neuroactive steroid composition have been observed opposite to those seen in depression. However, during experimentally induced panic induction either with cholecystokinine-tetrapeptide or sodium lactate, there was a pronounced decline in the concentrations of 3 alpha-reduced neuroactive steroids in patients with panic disorder, which might result in a decreased GABAergic tone. In contrast, no changes in neuroactive steroid concentrations could be observed in healthy controls with the exception of 3 alpha,5 alpha-tetrahydrodeoxycorticosterone. The modulation of GABA(A) receptors by neuroactive steroids might contribute to the pathophysiology of depression and anxiety disorders and might offer new targets for the development of novel anxiolytic compounds. Copyright (c) 2006 S. Karger AG, Basel

Engaging fathers in child welfare services: a narrative review of recent research evidence

It is widely recognized as problematic that there are generally low levels of engagement with child welfare services from biological and social fathers. The result can be limited resources for children's care and potentially poor risk assessment and management. This paper reviews the published research from 2000 to 2010 about the barriers to and facilitators of better father engagement, as well as the very limited evidence on the effectiveness of work with maltreating fathers. There is relatively little known about what works in engaging men, but there are some promising indicators from family support and child protection practice contexts. These include early identification and early involvement of fathers; a proactive approach, including an insistence on men's involvement with services; and the use of practical activities. In the light of what is known about the characteristics of maltreating fathers, there is a logical fit with cognitive‐behavioural approaches. Although there is no direct evidence of the effectiveness of motivational interviewing in this context, its effectiveness in allied fields of practice would suggest that it may hold some promise for the initial engagement of fathers who pose a risk to children.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90556/1/j.1365-2206.2012.00827.x.pd

Engineering serendipity: high-throughput discovery of materials that resist bacterial attachment

Controlling the colonisation of materials by microorganisms is important in a wide range of industries and clinical settings. To date, the underlying mechanisms that govern the interactions of bacteria with material surfaces remain poorly understood, limiting the ab initio design and engineering of biomaterials to control bacterial attachment. Combinatorial approaches involving high-throughput screening have emerged as key tools for identifying materials to control bacterial attachment. The hundreds of different materials assessed using these methods can be carried out with the aid of computational modelling. This approach can develop an understanding of the rules used to predict bacterial attachment to surfaces of non-toxic synthetic materials. Here we outline our view on the state of this field and the challenges and opportunities in this area for the coming years

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure