Left main bronchus compression due to main pulmonary artery dilatation in pulmonary hypertension: two case reports

Abstract. Pulmonary arterial dilatation associated with pulmonary hypertension may result in significant compression of local structures. Left main coronary artery and left recurrent laryngeal nerve compression have been described. Tracheobronchial compression from pulmonary arterial dilatation is rare in adults, and there are no reports in the literature of its occurrence in idiopathic pulmonary arterial hypertension. Compression in infants with congenital heart disease has been well described. We report 2 cases of tracheobronchial compression: first, an adult patient with idiopathic pulmonary arterial hypertension who presents with symptomatic left main bronchus compression, and second, an adult patient with Eisenmenger ventricular septal defect and right-sided aortic arch, with progressive intermedius and right middle lobe bronchi compression in association with enlarged pulmonary arteries

A qualitative exploration of UK prisoners’ experiences of substance misuse and mental health difficulties, and the Breaking Free Health and Justice interventions

This qualitative study explored prisoners’ lived experiences of substance use and mental health difficulties and aimed to examine perceived links between these two areas and how they might be associated with recovery during engagement with the Breaking Free Health and Justice (BFHJ) treatment programs. Interviews were conducted with 32 prisoners receiving treatment for substance use in North-West England. Emerging from prisoners’ interviews were themes relating to difficult life experiences from childhood into adulthood, how these experiences played a role in the emergence of their multiple and complex difficulties, their treatment experiences, and how their current involvement with the criminal justice system acted as a catalyst for positive change, including engagement with the BFHJ programs. This study identified the roles of substance use and mental health difficulties in the lives of participants, identified how their multiple and complex difficulties might be addressed, and provided insights into prisoners’ interpretations of their life experiences

Initial findings from a mixed-methods feasibility and effectiveness evaluation of the 'Breaking Free Health an Justice' treatment and recovery programme for substance misuse in prison settings

Reshaping substance misuse treatment in prisons is central to the UK Government’s drive to address substance dependence in the prison population and reduce substance-related offending and recidivism. Therefore, a through-care project to support prisoners released from custody to community, “Gateways”, is taking place across North-West England. Amongst support with housing, education, training and employment, Gateways incorporates the Breaking Free Online (BFO) substance misuse treatment programme. Aims: To explore BFO’s potential to provide support to prisoners’ substance misuse recovery and continuity of care post-release, and examine quantitative outcomes provided by prisoners who have used the programme. Methods: Qualitative interviews with prisoners and analyses of quantitative psychometric data collected pre- and post-intervention. Findings: Themes emerging from qualitative data around prisoners’ experiences of engaging with BFO illustrate its potential for use in prison settings and also upon release to the community. Significant quantitative improvements to quality of life, severity of substance dependence and aspects of recovery progression illustrate initial effectiveness of BFO. Conclusions: The BFO programme demonstrates potential in providing effective treatment for offenders with substance misuse difficulties, and specifically in delivering continuity of care following release to the community

Diurnal rhythms in the human urine metabolome during sleep and total sleep deprivation

Understanding how metabolite levels change over the 24 hour day is of crucial importance for clinical and epidemiological studies. Additionally, the association between sleep deprivation and metabolic disorders such as diabetes and obesity requires investigation into the links between sleep and metabolism. Here, we characterise time-of-day variation and the effects of sleep deprivation on urinary metabolite profiles. Healthy male participants (n = 15) completed an in-laboratory study comprising one 24 h sleep/wake cycle prior to 24 h of continual wakefulness under highly controlled environmental conditions. Urine samples were collected over set 2-8 h intervals and analysed by (1)H NMR spectroscopy. Significant changes were observed with respect to both time of day and sleep deprivation. Of 32 identified metabolites, 7 (22%) exhibited cosine rhythmicity over at least one 24 h period; 5 exhibiting a cosine rhythm on both days. Eight metabolites significantly increased during sleep deprivation compared with sleep (taurine, formate, citrate, 3-indoxyl sulfate, carnitine, 3-hydroxyisobutyrate, TMAO and acetate) and 8 significantly decreased (dimethylamine, 4-DTA, creatinine, ascorbate, 2-hydroxyisobutyrate, allantoin, 4-DEA, 4-hydroxyphenylacetate). These data indicate that sampling time, the presence or absence of sleep and the response to sleep deprivation are highly relevant when identifying biomarkers in urinary metabolic profiling studies

Pyridine-3-carboxamide-6-yl-ureas as novel inhibitors of bacterial DNA gyrase: Structure based design, synthesis, SAR and antimicrobial activity

The development of antibacterial drugs based on novel chemotypes is essential to the future management of serious drug resistant infections. We herein report the design, synthesis and SAR of a novel series of N-ethylurea inhibitors based on a pyridine-3-carboxamide scaffold targeting the ATPase sub-unit of DNA gyrase. Consideration of structural aspects of the GyrB ATPase site has aided the development of this series resulting in derivatives that demonstrate excellent enzyme inhibitory activity coupled to potent Gram positive antibacterial efficacy

Using the ‘recovery’ and ‘rehabilitation’ paradigms to support desistence of substance-involved offenders: Exploration of dual and multi-focus interventions (Invited Paper)

Purpose The links between substance use and offending are well evidenced in the literature, and increasingly, substance misuse recovery is being seen as a central component of the process of rehabilitation from offending, with substance use identified as a key criminogenic risk factor. In recent years, research has demonstrated the commonalities between recovery and rehabilitation, and the possible merits of providing interventions to substance-involved offenders that address both problematic sets of behaviours. The purpose of this paper is to provide an overview of the links between substance use and offending, and the burgeoning literature around the parallel processes of recovery and rehabilitation. Design/methodology/approach This is provided as a rationale for a new treatment approach for substance-involved offenders, Breaking Free Online (BFO), which has recently been provided as part of the “Gateways” throughcare pathfinder in a number of prisons in North-West England. The BFO programme contains specific behaviour change techniques that are generic enough to be applied to change a wide range of behaviours, and so is able to support substance-involved offenders to address their substance use and offending simultaneously. Findings This dual and multi-target intervention approach has the potential to address multiple, associated areas of need simultaneously, streamlining services and providing more holistic support for individuals, such as substance-involved offenders, who may have multiple and complex needs. Practical implications Given the links between substance use and offending, it may be beneficial to provide multi-focussed interventions that address both these behaviours simultaneously, in addition to other areas of multiple and complex needs. Specifically, digital technologies may provide an opportunity to widen access to such multi-focussed interventions, through computer-assisted therapy delivery modalities. Additionally, using digital technologies to deliver such interventions can provide opportunities for joined-up care by making interventions available across both prison and community settings, following offenders on their journey through the criminal justice system. Originality/value Recommendations are provided to other intervention developers who may wish to further contribute to widening access to such dual- and multi-focus programmes for substance-involved offenders, based on the experiences developing and evidencing the BFO programme

The Zero-Point Field and Inertia

A brief overview is presented of the basis of the electromagnetic zero-point field in quantum physics and its representation in stochastic electrodynamics. Two approaches have led to the proposal that the inertia of matter may be explained as an electromagnetic reaction force. The first is based on the modeling of quarks and electrons as Planck oscillators and the method of Einstein and Hopf to treat the interaction of the zero-point field with such oscillators. The second approach is based on analysis of the Poynting vector of the zero-point field in accelerated reference frames. It is possible to derive both Newton's equation of motion, F=ma, and its relativistic co-variant form from Maxwell's equations as applied to the zero-point field of the quantum vacuum. This appears to account, at least in part, for the inertia of matter.Comment: 8 pages, no fig

Expanding the Anti-Phl p 7 Antibody Toolkit: An Anti-Idiotype Nanobody Inhibitor.

We have previously produced a toolkit of antibodies, comprising recombinant human antibodies of all but one of the human isotypes, directed against the polcalcin family antigen Phl p 7. In this work, we complete the toolkit of human antibody isotypes with the IgD version of the anti-Phl p 7 monoclonal antibody. We also raised a set of nanobodies against the IgD anti-Phl p 7 antibody and identify and characterize one paratope-specific nanobody. This nanobody also binds to the IgE isotype of this antibody, which shares the same idiotype, and orthosterically inhibits the interaction with Phl p 7. The 2.1 Å resolution X-ray crystal structure of the nanobody in complex with the IgD Fab is described

Effects of stitching on delamination of satin weave carbon-epoxy laminates under mode I, mode II and mixed-mode I/II loadings

The objective of the present study is to characterize the effect of modified chain stitching on the delamination growth under mixed-mode I/II loading conditions. Delamination toughness under mode I is experimentally determined, for unstitched and stitched laminates, by using untabbed and tabbed double cantilever beam (TDCB) tests. The effect of the reinforcing tabs on mode I toughness is investigated. Stitching improves the energy release rate (ERR) up to 4 times in mode I. Mode II delamination toughness is evaluated in end-notched flexure (ENF) tests. Different geometries of stitched specimens are tested. Crack propagation occurs without any failure of stitching yarns. The final crack length attains the mid-span or it stops before and the specimen breaks in bending. The ERR is initially low and gradually increases with crack length to very high values. The mixedmode delamination behaviour is investigated using a mixed-mode bending (MMB) test. For unstitched specimens, a simple mixed-mode criterion is identified. For stitched specimens, stitching yarns do not break during 25% of mode I ratio tests and the ERR increase is relatively small compared to unstitched values. For 70% and 50% of mode I ratios, failures of yarns are observed during crack propagation and tests are able to capture correctly the effect of the stitching: it clearly improves the ERR for these two mixed modes, as much as threefold

A study of empyema thoracis and role of intrapleural streptokinase in its management

BACKGROUND: Clinical spectrum, microbiology and outcome of empyema thoracis are changing. Intrapleural instillation of fibrinolytic agents is being increasingly used for management of empyema thoracis. The present study was carried out to describe the clinical profile and outcome of patients with empyema thoracis including those with chronic empyema and to study the efficacy and safety of intrapleural streptokinase in its management. METHODS: Clinical profile, etiological agents, hospital course and outcome of 31 patients (mean age 40 ± 16 years, M: F 25: 6) with empyema thoracis treated from 1998 to 2003 was analyzed. All patients were diagnosed on the basis of aspiration of frank pus from pleural cavity. Clinical profile, response to therapy and outcome were compared between the patients who received intrapleural streptokinase (n = 12) and those who did not (n = 19). RESULTS: Etiology was tubercular in 42% of the patients (n = 13) whereas the rest were bacterial. Amongst the patients in which organisms could be isolated (n = 13, 42%) Staphylococcus aureus was the commonest (n = 5). Intrapleural streptokinase was instilled in 12 patients. This procedure resulted in increase of drainage of pleural fluid in all patients. Mean daily pleural fluid drainage after streptokinase instillation was significantly higher for patients who received intrapleural streptokinase than those who did not (213 ml vs 57 ml, p = 0.006). Only one patient who was instilled streptokinase eventually required decortication, which had to be done in five patients (16.1%). Mean hospital stay was 30.2 ± 17.6 days whereas two patients died. CONCLUSIONS: Tubercular empyema is common in Indian patients. Intrapleural streptokinase appears to be a useful strategy to preserve lung function and reduce need for surgery in patients with late stage of empyema thoracis