The introduction of the TMPG fails charge for U.S. Treasury securities

The TMPG fails charge for U.S. Treasury securities provides that a buyer of Treasury securities can claim monetary compensation from the seller if the seller fails to deliver the securities on a timely basis. The charge was introduced in May 2009 and replaced an existing market convention of simply postponing—without any explicit penalty and at an unchanged invoice price—a seller’s obligation to deliver Treasury securities if the seller fails to deliver the securities on a scheduled settlement date. This article explains how a proliferation of settlement fails following the insolvency of Lehman Brothers Holdings Inc. in September 2008 led the Treasury Market Practices Group (TMPG)—a group of market professionals committed to supporting the integrity and efficiency of the U.S. Treasury market—to promote a change in the existing market convention. The change—the introduction of the fails charge—was significant because it mitigated an important dysfunctionality in the secondary market for U.S. Treasury securities and because it stands as an example of the value of cooperation between the public and private sectors in responding to altered market conditions in a flexible, timely, and innovative fashion.Treasury bonds ; Government securities ; Clearing of securities ; Secondary markets

Extensive Genomic Diversity among Bovine-Adapted Staphylococcus aureus: Evidence for a Genomic Rearrangement within CC97

peer-reviewedStaphylococcus aureus is an important pathogen associated with both human and veterinary disease and is a common cause of bovine mastitis. Genomic heterogeneity exists between S. aureus strains and has been implicated in the adaptation of specific strains to colonise particular mammalian hosts. Knowledge of the factors required for host specificity and virulence is important for understanding the pathogenesis and management of S. aureus mastitis. In this study, a panel of mastitis-associated S. aureus isolates (n = 126) was tested for resistance to antibiotics commonly used to treat mastitis. Over half of the isolates (52%) demonstrated resistance to penicillin and ampicillin but all were susceptible to the other antibiotics tested. S. aureus isolates were further examined for their clonal diversity by Multi-Locus Sequence Typing (MLST). In total, 18 different sequence types (STs) were identified and eBURST analysis demonstrated that the majority of isolates grouped into clonal complexes CC97, CC151 or sequence type (ST) 136. Analysis of the role of recombination events in determining S. aureus population structure determined that ST diversification through nucleotide substitutions were more likely to be due to recombination compared to point mutation, with regions of the genome possibly acting as recombination hotspots. DNA microarray analysis revealed a large number of differences amongst S. aureus STs in their variable genome content, including genes associated with capsule and biofilm formation and adhesion factors. Finally, evidence for a genomic arrangement was observed within isolates from CC97 with the ST71-like subgroup showing evidence of an IS431 insertion element having replaced approximately 30 kb of DNA including the ica operon and histidine biosynthesis genes, resulting in histidine auxotrophy. This genomic rearrangement may be responsible for the diversification of ST71 into an emerging bovine adapted subgroup

Experiences of young people living with mental health difficulties in the context of COVID-19 and the role of integrated social care and mental health services in providing support

Background: Youth is a time associated with significant change and mental health difficulties are most likely to be diagnosed between the ages of 16-25. This means there is a need to ensure that young people, particularly those with complex or social care needs, have access to the right support. COVID-19 has resulted in significant upheaval for young people and those with pre-existing mental health difficulties may have been impacted differently than the general population. Methods: A systematic review was undertaken to identify the evidence of integrated mental health and social care’s ability to improve clinical effectiveness, cost efficiency and service user experience. A qualitative study was undertaken to understand more about the experiences of young people with pre-existing mental health conditions of the COVID-19 pandemic. Results: The review identified twelve studies which met the inclusion criteria including intervention evaluations, qualitative studies and a discreet choice experiment survey. Eleven studies took place outside of the UK. The results found evidence to support that integrated mental health and social care improves service user experience, limited evidence to support clinical effectiveness and no evaluation of cost efficiency. The empirical paper found that in young people with pre-existing mental health difficulties, the pandemic had impacted their mental health, and their responses to the pandemic had been affected by their mental health. Though this had made coping more difficult, the sample were also able to use their experiences of managing their mental health to cope with the pandemic, and for some participants the pandemic had supported them to make meaningful changes Conclusions: The review identified that outside of improving service-user experience, evidence is currently lacking to support integrated mental health and social care as improving support for young people. Services in this area are continuing to change following the impact of COVID-19 and the development of integrated services across the NHS which may allow for further research to take place. The qualitative study suggests that young people could be well supported using a strengths-based model, facilitating developing coping skills and building on positive changes

Schizophrenia, recovery and the self: An introduction to the special issue on metacognition

In this special issue, work is presented linking metacognition among persons with schizophrenia with a range of psychosocial outcomes including vocational functioning, empathy, motivation, self-evaluation, and other cognitive functions. This overview will highlight how these works allow for the quantitative study of processes which underpin alterations in self-experience in schizophrenia, which in turn allows self-experience to be studied as part of a larger set of brain-based and social phenomena whose interaction influences the trajectory of one's life and illness. We explore the hypothesis that metacognitive capacity, as a node in a larger biopsychosocial network, may be accessible by psychosocial treatment and, if successfully targeted, may disrupt the processes which perpetuate disability. Limitations and directions for future research are also discussed

A systematic review of treating recurrent head and neck cancer: a reintroduction of brachytherapy with or without surgery.

Purpose: To review brachytherapy use in recurrent head and neck carcinoma (RHNC) with focus on its efficacy and complication rates. Material and methods: A literature search of PubMed, Ovid, Google Scholar, and Scopus was conducted from 1990 to 2017. Publications describing treatment of RHNC with brachytherapy with or without surgery were included. The focus of this review is on oncologic outcomes and the safety of brachytherapy in the recurrent setting. Results: Thirty studies involving RHNC treatment with brachytherapy were reviewed. Brachytherapy as adjunctive treatment to surgical resection appears to be associated with an improved local regional control and overall survival, when compared with the published rates for re-irradiation utilizing external beam radiotherapy (RT) or brachytherapy alone. Safety data remains variable with different isotopes and dose rates with implantable brachytherapy demonstrating a tolerable side effect profile. Conclusions: Although surgery remains a mainstay treatment for RHNC, intraoperative interstitial brachytherapy delivery as adjunctive therapy may improve the treatment outcome and may be associated with fewer complication rates as compared to reirradiation using external beam radiotherapy. Further investigations are required to elucidate the role of brachytherapy for RHNC

Interactive versus Passive Distraction and Parent Psychoeducation as pain management techniques during pediatric venepuncture: A Randomized Controlled Trial

Objectives The aim of this research was twofold: to explore 1) the efficacy of active vs. passive distraction on self-reported pain and distress of children during a venepuncture; and 2) the impact ofparental psychoeducation on child and parent outcomes, parental knowledge of distraction procedures and parental engagement in effective pain management strategies.  Methods This cross-sectional study included 213 children scheduled for a venepuncture, and one of their parents, who were randomly allocated to one of four conditions; interactive distraction, passive distraction, interactive distraction with parent psychoeducation and passive distraction with parent psychoeducation. ANCOVA’s were used to investigate the impact of distraction type and the use of parent psychoeducation on child and parent pain related outcome variables.  Results Statistical analyses revealed no significant differences between groups for child-reported pain and distress. Parents who received parent psychoeducation had a significantly higher level of knowledge than parents who did not receive psychoeducation, but did not engage in more effective pain management behaviour.  Conclusions The results indicated that passive vs. active distraction does not have a significantly different influence on child pain-related outcome variables. In addition, while psychoeducation was demonstrated to be effective in increasing parental knowledge, it was not sufficient to change parental behaviour

Prostaglandin F2α regulates mitochondrial dynamics and mitophagy in the bovine corpus luteum

Prostaglandins are arachidonic acid-derived lipid mediators involved in numerous physiological and pathological processes. PGF2α analogues are therapeutically used for regulating mammalian reproductive cycles and blood pressure, inducing term labor, and treating ocular disorders. PGF2α exerts effects via activation of calcium and PKC signaling, however, little is known about the cellular events imposed by PGF2α signaling. Here, we explored the early effects of PGF2α on mitochondrial dynamics and mitophagy in the bovine corpus luteum employing relevant and well characterized in vivo and in vitro approaches. We identified PKC/ERK and AMPK as critical protein kinases essential for activation of mitochondrial fission proteins, DRP1 and MFF. Furthermore, we report that PGF2α elicits increased intracellular reactive oxygen species and promotes receptormediated activation of PINK–Parkin mitophagy. These findings place the mitochondrium as a novel target in response to luteolytic mediator, PGF2α. Understanding intracellular processes occurring during early luteolysis may serve as a target for improving fertility

Twelve years of SAMtools and BCFtools.

BACKGROUND: SAMtools and BCFtools are widely used programs for processing and analysing high-throughput sequencing data. They include tools for file format conversion and manipulation, sorting, querying, statistics, variant calling, and effect analysis amongst other methods. FINDINGS: The first version appeared online 12 years ago and has been maintained and further developed ever since, with many new features and improvements added over the years. The SAMtools and BCFtools packages represent a unique collection of tools that have been used in numerous other software projects and countless genomic pipelines. CONCLUSION: Both SAMtools and BCFtools are freely available on GitHub under the permissive MIT licence, free for both non-commercial and commercial use. Both packages have been installed >1 million times via Bioconda. The source code and documentation are available from https://www.htslib.org

Visual dysfunction is a better predictor than retinal thickness for dementia in Parkinson's disease

BACKGROUND: Dementia is a common and devastating symptom of Parkinson's disease (PD). Visual function and retinal structure are both emerging as potentially predictive for dementia in Parkinson's but lack longitudinal evidence. METHODS: We prospectively examined higher order vision (skew tolerance and biological motion) and retinal thickness (spectral domain optical coherence tomography) in 100 people with PD and 29 controls, with longitudinal cognitive assessments at baseline, 18 months and 36 months. We examined whether visual and retinal baseline measures predicted longitudinal cognitive scores using linear mixed effects models and whether they predicted onset of dementia, death and frailty using time-to-outcome methods. RESULTS: Patients with PD with poorer baseline visual performance scored lower on a composite cognitive score (β=0.178, SE=0.05, p=0.0005) and showed greater decreases in cognition over time (β=0.024, SE=0.001, p=0.013). Poorer visual performance also predicted greater probability of dementia (χ² (1)=5.2, p=0.022) and poor outcomes (χ² (1) =10.0, p=0.002). Baseline retinal thickness of the ganglion cell-inner plexiform layer did not predict cognitive scores or change in cognition with time in PD (β=-0.013, SE=0.080, p=0.87; β=0.024, SE=0.001, p=0.12). CONCLUSIONS: In our deeply phenotyped longitudinal cohort, visual dysfunction predicted dementia and poor outcomes in PD. Conversely, retinal thickness had less power to predict dementia. This supports mechanistic models for Parkinson's dementia progression with onset in cortical structures and shows potential for visual tests to enable stratification for clinical trials