An intensity-expansion method to treat non-stationary time series: an application to the distance between prime numbers

We study the fractal properties of the distances between consecutive primes. The distance sequence is found to be well described by a non-stationary exponential probability distribution. We propose an intensity-expansion method to treat this non-stationarity and we find that the statistics underlying the distance between consecutive primes is Gaussian and that, by transforming the distance sequence into a stationary one, the range of Gaussian randomness of the sequence increases.Comment: 11 pages, 7 figures, in press on 'Chaos, Solitons & Fractals

A new family of phosphoinositide phosphatases in microorganisms: identification and biochemical analysis

<p>Abstract</p> <p>Background</p> <p>Phosphoinositide metabolism is essential to membrane dynamics and impinges on many cellular processes, including phagocytosis. Modulation of phosphoinositide metabolism is important for pathogenicity and virulence of many human pathogens, allowing them to survive and replicate in the host cells. Phosphoinositide phosphatases from bacterial pathogens are therefore key players in this modulation and constitute attractive targets for chemotherapy. MptpB, a virulence factor from <it>Mycobacterium tuberculosis</it>, has phosphoinositide phosphatase activity and a distinct active site P-loop signature HCXXGKDR that shares characteristics with eukaryotic lipid phosphatases and protein tyrosine phosphatases. We used this P-loop signature as a "diagnostic motif" to identify related putative phosphatases with phosphoinositide activity in other organisms.</p> <p>Results</p> <p>We found more than 200 uncharacterised putative phosphatase sequences with the conserved signature in bacteria, with some related examples in fungi and protozoa. Many of the sequences identified belong to recognised human pathogens. Interestingly, no homologues were found in any other organisms including Archaea, plants, or animals. Phylogenetic analysis revealed that these proteins are unrelated to classic eukaryotic lipid phosphatases. However, biochemical characterisation of those from <it>Listeria monocytogenes </it>and <it>Leishmania major</it>, demonstrated that, like MptpB, they have phosphatase activity towards phosphoinositides. Mutagenesis studies established that the conserved Asp and Lys in the P-loop signature (HCXXG<b>KD</b>R) are important in catalysis and substrate binding respectively. Furthermore, we provide experimental evidence that the number of basic residues in the P-loop is critical in determining activity towards poly-phosphoinositides.</p> <p>Conclusion</p> <p>This new family of enzymes in microorganisms shows distinct sequence and biochemical characteristics to classic eukaryotic lipid phosphatases and they have no homologues in humans. This study provides a foundation for examining the biological role of this new family of phosphatases and their potential as pharmaceutical targets against infectious diseases.</p

Comparative study of a vitrinite-rich and an inertinite-rich Witbank coal (South Africa) using pyrolysis-gas chromatography

Abstract This study aims to compare iso-rank vitrinite-rich and inertinite-rich coal samples to understand the impact of coal-forming processes on pyrolysis chemistry. A medium rank C bituminous coal was density-fractionated to create a vitrinite-rich and an inertinite-rich sub-sample. The vitrinite-rich sample has 83 vol% total vitrinite (mineral-matter-free basis), whereas the inertinite-rich counterpart has 66 vol% total inertinite. The vitrinite-rich sample is dominated by collotelinite and collodetrinite. Fusinite, semifusinite, and inertodetrinite are the main macerals of the inertinite-rich sample. Molecular chemistry was assessed using a pyrolysis gas chromatograph (py-GC) equipped with a thermal desorption unit coupled to a time of flight mass spectrometer (MS) (py-GC/MS) and solid-state nuclear magnetic resonance (13C CP-MAS SS NMR). The pyrolysis products of the coal samples are generally similar, comprised of low and high molecular weight alkanes, alkylbenzenes, alkylphenols, and alkyl-subtituted polycyclic aromatic hydrocarbons, although the vitrinite-rich sample is chemically more diverse. The lack of diversity exhibited by the inertinite-rich sample upon pyrolysis may be interpreted to suggest that major components were heated in their geologic history. Based on the 13C CP-MAS SS NMR analysis, the inertinite-rich sample has a greater fraction of phenolics, reflected in the py-GC/MS results as substituted and unsubstituted derivatives. The greater abundance of phenolics for the inertinite-rich sample may suggest a fire-related origin for the dominant macerals of this sample. The C2-alkylbenzene isomers (p-xylene and o-xylene) were detected in the pyrolysis products for the vitrinite-rich and inertinite-rich samples, though more abundant in the former. The presence of these in both samples likely reflects common source vegetation for the dominant vitrinite and inertinite macerals

Using Telemedicine to Provide Education for the Symptomatic Patient with Chronic Respiratory Disease

Technology-enabled learning, using computers, smartphones, and tablets, to educate patients on their respiratory disease and management has grown over the last decade. This shift has been accelerated by the global COVID-19 pandemic and the need to socially distance for public health. Thirteen recently published papers examined experience, knowledge, skills and attitude acquisition, behaviour change, and impact on health outcomes of patient education using technology (websites and mobile device applications) for people with chronic respiratory disease. Technology-enabled patient education that includes relevant information, with activities that encourage the patient to interact with the digital platform, appears to lead to better patient experience and may increase learning and behaviour change with improved quality of life. Developing online relationships with healthcare providers, lower digital capabilities, and poor access to a computer/smartphone/tablet, appear to be barriers that need to be overcome for equity in access. Maintaining the principles of quality educational design, ensuring interactive experiences for patient involvement in the educational activities, patient co-design, healthcare professionals connecting with experts in the field of technology-enabled learning for development of education models, and ongoing research lead to the best patient outcomes in technology-enabled education for respiratory disease

Glycosaminoglycan profiles of repair tissue formed following autologous chondrocyte implantation differ from control cartilage

Currently, autologous chondrocyte implantation (ACI) is the most commonly used cell-based therapy for the treatment of isolated femoral condyle lesions of the knee. A small number of centres performing ACI have reported encouraging long-term clinical results, but there is currently a lack of quantitative and qualitative biochemical data regarding the nature of the repair tissue. Glycosaminoglycan (GAG) structure influences physiological function and is likely to be important in the long-term stability of the repair tissue. The objective of this study was to use fluorophore-assisted carbohydrate electrophoresis (FACE) to both quantitatively and qualitatively analyse the GAG composition of repair tissue biopsies and compare them with age-matched cadaveric controls. We used immunohistochemistry to provide a baseline reference for comparison. Biopsies were taken from eight patients (22 to 52 years old) 1 year after ACI treatment and from four cadavers (20 to 50 years old). FACE quantitatively profiled the GAGs in as little as 5 μg of cartilage. The pattern and intensity of immunostaining were generally comparable with the data obtained with FACE. In the ACI repair tissue, there was a twofold reduction in chondroitin sulphate and keratan sulphate compared with age-matched control cartilage. By contrast, there was an increase in hyaluronan with significantly shorter chondroitin sulphate chains and less chondroitin 6-sulphate in repair tissue than control cartilage. The composition of the repair tissue thus is not identical to mature articular cartilage

B-type natriuretic peptide-guided treatment for heart failure

Background Heart failure is a condition in which the heart does not pump enough blood to meet all the needs of the body. Symptoms of heart failure include breathlessness, fatigue and fluid retention. Outcomes for patients with heart failure are highly variable; however on average, these patients have a poor prognosis. Prognosis can be improved with early diagnosis and appropriate use of medical treatment, use of devices and transplantation. Patients with heart failure are high users of healthcare resources, not only due to drug and device treatments, but due to high costs of hospitalisation care. B‐type natriuretic peptide levels are already used as biomarkers for diagnosis and prognosis of heart failure, but could offer to clinicians a possible tool to guide drug treatment. This could optimise drug management in heart failure patients whilst allaying concerns over potential side effects due to drug intolerance. Objectives To assess whether treatment guided by serial BNP or NT‐proBNP (collectively referred to as NP) monitoring improves outcomes compared with treatment guided by clinical assessment alone. Search methods Searches were conducted up to 15 March 2016 in the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (OVID), Embase (OVID), the Database of Abstracts of Reviews of Effects (DARE) and the NHS Economic Evaluation Database in the Cochrane Library. Searches were also conducted in the Science Citation Index Expanded, the Conference Proceedings Citation Index on Web of Science (Thomson Reuters), World Health Organization International Clinical Trials Registry and ClinicalTrials.gov. We applied no date or language restrictions. Selection criteria We included randomised controlled trials of NP‐guided treatment of heart failure versus treatment guided by clinical assessment alone with no restriction on follow‐up. Adults treated for heart failure, in both in‐hospital and out‐of‐hospital settings, and trials reporting a clinical outcome were included. Data collection and analysis Two review authors independently selected studies for inclusion, extracted data and evaluated risk of bias. Risk ratios (RR) were calculated for dichotomous data, and pooled mean differences (MD) (with 95% confidence intervals (CI)) were calculated for continuous data. We contacted trial authors to obtain missing data. Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, we assessed the quality of the evidence and GRADE profiler (GRADEPRO) was used to import data from Review Manager to create a 'Summary of findings' table. Main results We included 18 randomised controlled trials with 3660 participants (range of mean age: 57 to 80 years) comparing NP‐guided treatment with clinical assessment alone. The evidence for all‐cause mortality using NP‐guided treatment showed uncertainty (RR 0.87, 95% CI 0.76 to 1.01; patients = 3169; studies = 15; low quality of the evidence), and for heart failure mortality (RR 0.84, 95% CI 0.54 to 1.30; patients = 853; studies = 6; low quality of evidence). The evidence suggested heart failure admission was reduced by NP‐guided treatment (38% versus 26%, RR 0.70, 95% CI 0.61 to 0.80; patients = 1928; studies = 10; low quality of evidence), but the evidence showed uncertainty for all‐cause admission (57% versus 53%, RR 0.93, 95% CI 0.84 to 1.03; patients = 1142; studies = 6; low quality of evidence). Six studies reported on adverse events, however the results could not be pooled (patients = 1144; low quality of evidence). Only four studies provided cost of treatment results, three of these studies reported a lower cost for NP‐guided treatment, whilst one reported a higher cost (results were not pooled; patients = 931, low quality of evidence). The evidence showed uncertainty for quality of life data (MD ‐0.03, 95% CI ‐1.18 to 1.13; patients = 1812; studies = 8; very low quality of evidence). We completed a 'Risk of bias' assessment for all studies. The impact of risk of bias from lack of blinding of outcome assessment and high attrition levels was examined by restricting analyses to only low 'Risk of bias' studies. Authors' conclusions In patients with heart failure low‐quality evidence showed a reduction in heart failure admission with NP‐guided treatment while low‐quality evidence showed uncertainty in the effect of NP‐guided treatment for all‐cause mortality, heart failure mortality, and all‐cause admission. Uncertainty in the effect was further shown by very low‐quality evidence for patient's quality of life. The evidence for adverse events and cost of treatment was low quality and we were unable to pool results.</p

Factors influencing fatigue in UK nurses working in respiratory clinical areas during the second wave of the Covid‐19 pandemic: An online survey

AIMS AND OBJECTIVES: This study explores UK nurses' experiences of working in a respiratory clinical area during the COVID‐19 pandemic over winter 2020. BACKGROUND: During the first wave of the pandemic, nurses working in respiratory clinical areas experienced significant levels of anxiety and depression. As the pandemic has progressed, levels of fatigue in nurses have not been assessed. METHODS: A cross‐sectional e‐survey was distributed via professional respiratory societies and social media. The survey included Generalised Anxiety Disorder Assessment (GAD7), Patient Health Questionnaire (PHQ9, depression), a resilience scale (RS‐14) and Chalder mental and physical fatigue tools. The STROBE checklist was followed as guidance to write the manuscript. RESULTS: Despite reporting anxiety and depression, few nurses reported having time off work with stress, most were maintaining training and felt prepared for COVID challenges in their current role. Nurses reported concerns over safety and patient feedback was both positive and negative. A quarter of respondents reported wanting to leave nursing. Nurses experiencing greater physical fatigue reported higher levels of anxiety and depression. CONCLUSIONS: Nurses working in respiratory clinical areas were closely involved in caring for COVID‐19 patients. Nurses continued to experience similar levels of anxiety and depression to those found in the first wave and reported symptoms of fatigue (physical and mental). A significant proportion of respondents reported considering leaving nursing. Retention of nurses is vital to ensure the safe functioning of already overstretched health services. Nurses would benefit from regular mental health check‐ups to ensure they are fit to practice and receive the support they need to work effectively. RELEVANCE TO CLINICAL PRACTICE: A high proportion of nurses working in respiratory clinical areas have been identified as experiencing fatigue in addition to continued levels of anxiety, depression over winter 2020. Interventions need to be implemented to help provide mental health support and improve workplace conditions to minimise PTSD and burnout

The Role of Pharmacists in Caring for Young People with Chronic Illness

PurposeTo explore the perceived and potential roles of pharmacists in the care of young people aged 10-24 years with chronic illness, through the exemplar of juvenile arthritis, from the perspectives of UK community and hospital pharmacists, health service commissioners, rheumatology health professionals and lay advocates.MethodsA sequential mixed methods study design comprising: focus groups with community and hospital pharmacists; telephone interviews with pharmacy and rheumatology stakeholders and commissioners, and multidisciplinary group discussions to prioritize roles generated by the first two qualitative phases.ResultsThe high priority roles for pharmacists, identified by pharmacists and rheumatology staff, were: developing generic healthcare skills among young people; transferring information effectively across care interfaces; building trusting relationships with young people; helping young people to find credible online health information, and the need to develop specialist expertise. Participants identified associated challenges for pharmacists in supporting young people with chronic illness. These challenges included parents collecting prescription refills alone, thus reducing opportunities to engage, and pharmacist isolation from the wider healthcare team.ConclusionsThis study has led to the identification of specific enhancements to pharmacy services for young people which have received the endorsement of a wide range of stakeholders. These suggestions could inform the next steps in developing the contribution of community and hospital pharmacy to support young people with chronic illness in the optimal use of their medication

Behavioral Interventions Associated with Smoking Cessation in the Treatment of Tobacco Use

Tobacco smoke is the leading cause of preventable premature death worldwide. While the majority of smokers would like to stop, the habitual and addictive nature of smoking makes cessation difficult. Clinical guidelines suggest that smoking cessation interventions should include both behavioural support and pharmacotherapy (e.g. nicotine replacement therapy). This commentary paper focuses on the important role of behavioural interventions in encouraging and supporting smoking cessation attempts. Recent developments in the field are discussed, including ‘cut-down to quit’, the behaviour change techniques taxonomy (BCTT) and very brief advice (VBA) on smoking. The paper concludes with a discussion of the important role that health professionals can and should play in the delivery of smoking cessation intervention