The host galaxy of a fast radio burst.

In recent years, millisecond-duration radio signals originating in distant galaxies appear to have been discovered in the so-called fast radio bursts. These signals are dispersed according to a precise physical law and this dispersion is a key observable quantity, which, in tandem with a redshift measurement, can be used for fundamental physical investigations. Every fast radio burst has a dispersion measurement, but none before now have had a redshift measurement, because of the difficulty in pinpointing their celestial coordinates. Here we report the discovery of a fast radio burst and the identification of a fading radio transient lasting ~6 days after the event, which we use to identify the host galaxy; we measure the galaxy's redshift to be z = 0.492 ± 0.008. The dispersion measure and redshift, in combination, provide a direct measurement of the cosmic density of ionized baryons in the intergalactic medium of ΩIGM = 4.9 ± 1.3 per cent, in agreement with the expectation from the Wilkinson Microwave Anisotropy Probe, and including all of the so-called 'missing baryons'. The ~6-day radio transient is largely consistent with the radio afterglow of a short γ-ray burst, and its existence and timescale do not support progenitor models such as giant pulses from pulsars, and supernovae. This contrasts with the interpretation of another recently discovered fast radio burst, suggesting that there are at least two classes of bursts.

Personal dosimetry for positron emitters, and occupational exposures from clinical use of gallium-68.

The current status and issues regarding positron dosimetry in nuclear medicine are summarized. The suitability of the United Kingdom Health Security Agency extremity and eye beta-gamma personal thermoluminescence dosemeters are then considered. Monte Carlo modelling is performed to determine their responses and derive sets of calibration factors, along withHp(0.07) andHp(3) conversion coefficients, for carbon-11, nitrogen-13, oxygen-15, fluorine-18 and gallium-68 sources, which are commonly used in positron emission tomography (PET) computed tomography; data for these isotopes is assumed extrapolatable to other positron sources. It is found that the dosemeters are adequate for assessing exposures to PET radionuclides, even if their routine calibrations to caesium-137 were maintained. An idealized set of measurements representing gallium-68 exposure scenarios is then described, including reproducible mock-ups of individuals manipulating vials and syringes. Finally, a short case-study is presented that explores occupational doses during routine clinical use of gallium-68. The extremity dosemeter results demonstrated significant variations dependent upon the exposure conditions, with some seen to be comparatively large; whole-body and eye dose rates per activity were found to be lower. The importance of routine dose monitoring of workers is emphasized, with the need for a longer-termed follow-up study demonstrated.

Multidisciplinary guidelines for the management of paediatric tracheostomy emergencies.

Temporary and permanent tracheostomies are required in children to manage actual or anticipated long-term ventilatory support, to aid secretion management or to manage fixed upper airway obstruction. Tracheostomies may be required from the first few moments of life, with the majority performed in children < 4 years of age. Although similarities with adult tracheostomies are apparent, there are key differences when managing the routine and emergency care of children with tracheostomies. The National Tracheostomy Safety Project identified the need for structured guidelines to aid multidisciplinary clinical decision making during paediatric tracheostomy emergencies. These guidelines describe the development of a bespoke emergency management algorithm and supporting resources. Our aim is to reduce the frequency, nature and severity of paediatric tracheostomy emergencies through preparation and education of staff, parents, carers and patients.

Offenders with intellectual disabilities in prison: what happens when they leave?

BACKGROUND: People with intellectual disabilities, if convicted of offences, may be sentenced to prison, but little is known about their life when they are released. METHOD: This study followed up men with intellectual disabilities who were leaving prisons in England. RESULTS: The men were hard to contact, but 38 men were interviewed, on average 10 weeks after leaving prison. The men were living in a variety of situations and often were very under-occupied, with limited social networks. A total of 70% were above the clinical cut-off for anxiety, and 59.5% were above the clinical cut-off for depression. The men were receiving little support in the community, and many had been reinterviewed by police. CONCLUSIONS: Community teams need to provide better support to this very vulnerable group.

An investigation into the content validity of the Antimicrobial Self-Assessment Toolkit for NHS Trusts (ASAT v15a) using cognitive interviews with antimicrobial pharmacists.

WHAT IS KNOWN AND OBJECTIVE: The Antimicrobial Self-Assessment Toolkit for NHS Trusts (ASAT) was developed to evaluate the organizational strategies used to implement hospital-based antimicrobial stewardship programmes. An iterative approach was used to develop ASAT v15a, which has been previously investigated for face validity; however, further investigation into other types of validity was required. Therefore, the aim of this study was to investigate the content validity of ASAT v15a and hence modify and improve the content validity of the toolkit. METHODS: A purposive sample of eight antimicrobial pharmacists was interviewed using cognitive interviewing techniques from within the former North-west Strategic Health Authority in England. Respondents were asked to 'think aloud' and to verbally express their thought processes as they generated responses to each question with the ASAT. RESULTS: There were no cognitive difficulties reported by respondents in response to 26/83 (31·3%) questions within the ASAT. However, cognitive difficulties were reported by respondents at each stage of the cognitive processing pathway in response to 57/83 (68·7%) questions. These difficulties were comprehension/interpretation in 27/83 (32·5%) questions, information retrieval in 10/83 (12%) questions, judgment/decision in 6/83 (7·2%) questions and response generation/formatting in 13/83 (15·7%) questions. Other findings included disagreement with the weightings applied to 13/83 (15·7%) questions. Respondents recommended that these questions should be modified to reflect their impact on hospital-based antimicrobial stewardship programmes (ASPs). Based on these findings, modifications were made to ASAT v15a to produce the next iteration (ASAT v16). Furthermore, respondents indicated that the role of clinical microbiologists was underrepresented in the current version of the toolkit; therefore, seven proposed questions were drafted, based on a literature review. WHAT IS NEW AND CONCLUSION: Cognitive interviews were effectively able to detect problems encountered by respondents along the cognitive processing pathway by identifying words and/or phrases that required further modifications. Also, this method highlighted that there was a disparity between the respondents' interpretation and the ASAT developers' intent within some questions. Although respondents indicated that the toolkit evaluated the most pertinent components of ASPs, further modifications and testing would be required to improve its validity. These results highlight the importance of the inclusion of end-users in the development of reporting and/or evaluation tools or questionnaires.

Antibacterial usage in English NHS hospitals as part of a national Antimicrobial Stewardship Programme.

Antimicrobial resistance (AMR) has become a global problem for health care services, with fewer antimicrobials entering the market and some pathogenic organisms becoming resistant to commonly used antimicrobials. Antimicrobial stewardship (AS), including evidence-based standard setting, education and communication, and audits of practice, has become a key method of preventing the rise in the rise in AMR. Data on antibiotic consumption are often obtained through prospective and retrospective point prevalence audits of antibiotic usage, but such studies are very resource intensive and only provide a snapshot of consumption. The objective of the study reported here was to examine longitudinal total antibacterial usage at a national level and cross-sectional usage at an individual hospital trust level using a commercial database that captures antimicrobial prescribing from at least 99% of English hospital Trusts.

The use of Surgihoney to prevent or eradicate bacterial colonisation in dressing oncology long vascular lines.

OBJECTIVE: A pilot evaluation was performed to assess the effects of Surgihoney, an engineered honey with highly active antimicrobial activity, on bacterial colonisation in long lines in oncology patients. METHOD: This prospective service evaluation was conducted at Hampshire Hospitals NHS Foundation Trust (HHFT) in England, UK, between 2012 and 2013. The study population consisted of oncology patients with central intravenous lines who were receiving outpatient chemotherapy. All patients were offered line dressing with or without Surgihoney, applied to the line exit site. RESULTS: The primary outcome measure of the study was the presence or absence of bacterial colonisation of the line site. There were 30 patients in each arm - with or without Surgihoney. In the Surgihoney arm, 2 patients with existing line site colonisation were cleared of bacterial colonisation and none acquired colonisation during the study period. In the non-treatment arm, 6 patients were colonised at the line site prior to screening or during the evaluation. Bacterial colonisation was maintained throughout the period. CONCLUSION: Surgihoney is an effective antimicrobial line-site dressing, significantly reducing line site colonisation and eradicating existing colonisation. It was well tolerated by the patients. DECLARATION OF INTEREST: Surgihoney supplies were donated by Healing Honey International (HHI) who also provided some funding to Hampshire Hospitals Foundation Trust for microbiological investigation. MD and JC have provided clinical advice in an advisory capacity to HHI.

Circulating Angiogenic and Senescent T Lymphocytes in Ageing and Frailty.

BACKGROUND: There is a need to identify vascular and geroscience-relevant markers and mediators that can physiologically link ageing to vascular disease. There is evidence of specific T cell subsets, all influenced by age, that exert positive and negative effects on vascular health. CD31+, termed angiogenic T cells, have been linked to vascular repair whereas CD28null, termed senescent T cells, display pro-inflammatory and cytotoxic effector functions. OBJECTIVE: This study sought to determine the combined influence of increasing age and frailty status on these circulating CD31+ and CD28null T cell subsets. METHODS: This cross-sectional study recruited four different cohorts of men and women; young (20-30 years, n=22), older (65-75 years, n=17), robust non-frail (76+ years, n=17), and frail (76+ years, n=15) adults. Frailty was determined using the Fried Frailty method. T cell subsets were determined by whole blood flow cytometry based on the expression of CD3, CD4, CD8, CD31 and CD28. Cognitive impairment (CI) was measured via the Montreal Cognitive Assessment test. RESULTS: Whether expressed as circulating counts or as a % of total T cells, there was a progressive decrease (p<0.05) in CD31+ T cells with increasing age but paradoxically higher values (p<0.05) in the frail compared to the robust non-frail group. These changes were similar in the CD4+ and CD8+ fractions. CD28null T cells were considerably higher (p<0.05) in the frail compared to the robust non-frail group, including in the CD8+ (47% vs 29%, p<0.05) and CD4+ (4% vs 1%, p<0.05) fractions. CD28null T cell percentage was also higher (p<0.05) in those with moderate CI compared to mild CI and normal function. CONCLUSION: CD8+CD28null T cells are considerably elevated in frailty and with cognitive impairment and may serve as a useful target for intervention. Currently, the utility of CD31+ T cells as an ageing biomarker may be confined to healthy ageing cohorts.

Evidence-based decision-making in a climate of political expediency: insights from local government.

AIMS: Local authorities in England are responsible for public health and health promotion. This article sought to explore how research and decision-making co-exist in a local authority in England. METHODS: An Embedded Researcher was based within the local authority and used qualitative methodology to address the research aim. Interviews and focus groups were employed to ascertain a range of stakeholder views in the local authority. All transcripts were coded on NVivo 12 by the Embedded Researcher and two members of the research team cross-checked a sample for coding accuracy. Data were analysed using framework analysis. RESULTS: The data suggest several barriers to using research to inform decision-making in health promotion and public health. The study shows that research is valued in local authorities, but not always privileged - this is due to cultural factors and practical political reasons which often means that decisions need to be made expediently. Participants outlined a juxtaposition between academic credibility; timeliness to complete the research and the financial cost associated with it; against the independence and credibility that independent academics could bring. CONCLUSION: Policy formulation and delivery is an integral aspect of health promotion and critical to achieving improved population health and reductions in health inequalities. However, there exists tensions between gathering research evidence and making research-informed decisions. The article concludes by advocating the use of Embedded Researchers to fully understand how research is gathered and used to support public health and health promotion policymaking.

Development of the obstetric unanticipated difficult video-laryngoscopy algorithm through a quality improvement randomized open-label in situ simulation study.

BACKGROUND: Video-laryngoscopy is increasingly used during general anesthesia for emergency cesarean deliveries. Given the heightened risk of difficult tracheal intubation in obstetrics, addressing challenges in airway management is crucial. In this simulation study, we hypothesized that using a flexible bronchoscope would lead to securing the airway faster than the Eschmann introducer when either device is used in addition to video-laryngoscopy. METHODS: Twenty-eight anesthesia trainees (n=14/group) were randomized to use either one of the rescue devices and video-recorded in a simulated scenario of emergency cesarean delivery. The primary outcome was the time difference in establishing intubation; secondary outcomes were the differences in incidence of hypoxemia, need for bag and mask ventilation, and failed intubation between the two rescue devices. RESULTS: Mean (±SD) time to intubation using flexible bronchoscopy was shorter compared to using an Eschmann introducer (24 ±â€¯10 vs 86 ±â€¯35 s; P<0.0001; difference in mean 62 seconds, 95% CI 42 to 82 seconds). In the fiberoptic bronchoscopy group, there were no episodes of hypoxemia or need for bag and mask ventilation; in contrast both such events occurred frequently in the Eschmann introducer group (71%, 10/14); P=0.0002). All flexible bronchoscopy-aided intubations were established on the first attempt. The incidence of failed intubation was similar in both groups. CONCLUSIONS: Our data from simulated emergency tracheal intubation suggest that flexible bronchoscopy combined with video-laryngoscopy results in faster intubation time than using an Eschmann introducer combined with video-laryngoscopy.

Next-generation precision medicine for suicidality prevention.

Suicidality remains a clear and present danger in society in general, and for mental health patients in particular. Lack of widespread use of objective and/or quantitative information has hampered treatment and prevention efforts. Suicidality is a spectrum of severity from vague thoughts that life is not worth living, to ideation, plans, attempts, and completion. Blood biomarkers that track suicidality risk provide a window into the biology of suicidality, as well as could help with assessment and treatment. Previous studies by us were positive. Here we describe new studies we conducted transdiagnostically in psychiatric patients, starting with the whole genome, to expand the identification, prioritization, validation and testing of blood gene expression biomarkers for suicidality, using a multiple independent cohorts design. We found new as well as previously known biomarkers that were predictive of high suicidality states, and of future psychiatric hospitalizations related to them, using cross-sectional and longitudinal approaches. The overall top increased in expression biomarker was SLC6A4, the serotonin transporter. The top decreased biomarker was TINF2, a gene whose mutations result in very short telomeres. The top biological pathways were related to apoptosis. The top upstream regulator was prednisolone. Taken together, our data supports the possibility that biologically, suicidality is an extreme stress-driven form of active aging/death. Consistent with that, the top subtypes of suicidality identified by us just based on clinical measures had high stress and high anxiety. Top therapeutic matches overall were lithium, clozapine and ketamine, with lithium stronger in females and clozapine stronger in males. Drug repurposing bioinformatic analyses identified the potential of renin-angiotensin system modulators and of cyclooxygenase inhibitors. Additionally, we show how patient reports for doctors would look based on blood biomarkers testing, personalized by gender. We also integrated with the blood biomarker testing social determinants and psychological measures (CFI-S, suicidal ideation), showing synergy. Lastly, we compared that to machine learning approaches, to optimize predictive ability and identify key features. We propose that our findings and comprehensive approach can have transformative clinical utility.

The impact of patient-reported frailty on cardiovascular outcomes in elderly patients after non-ST-acute coronary syndrome.

BACKGROUND: As life expectancy increases, the population of older individuals with coronary artery disease and frailty is growing. We aimed to assess the impact of patient-reported frailty on the treatment and prognosis of elderly early survivors of non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: Frailty data were obtained from two prospective trials, POPular Age and the POPular Age Registry, which both assessed elderly NSTE-ACS patients. Frailty was assessed one month after admission with the Groningen Frailty Indicator (GFI) and was defined as a GFI-score of 4 or higher. In these early survivors of NSTE-ACS, we assessed differences in treatment and 1-year outcomes between frail and non-frail patients, considering major adverse cardiovascular events (MACE, including cardiovascular mortality, myocardial infarction, and stroke) and major bleeding. RESULTS: The total study population consisted of 2192 NSTE-ACS patients, aged ≥70 years. The GFI-score was available in 1320 patients (79 ± 5 years, 37% women), of whom 712 (54%) were considered frail. Frail patients were at higher risk for MACE than non-frail patients (9.7% vs. 5.1%, adjusted hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.01-2.43, p = 0.04), but not for major bleeding (3.7% vs. 2.8%, adjusted HR 1.23, 95% CI 0.65-2.32, p = 0.53). Cubic spline analysis showed a gradual increase of the risk for clinical outcomes with higher GFI-scores. CONCLUSIONS: In elderly NSTE-ACS patients who survived 1-month follow-up, patient-reported frailty was independently associated with a higher risk for 1-year MACE, but not with major bleeding. These findings emphasize the importance of frailty screening for risk stratification in elderly NSTE-ACS patients.

Comparison of circumferential resection margin clearance criteria with survival after surgery for cancer of esophagus.

BACKGROUND: Circumferential resection margin (CRM) is widely recognized as an important prognostic factor in esophageal cancer. The aim of this study was to evaluate the clinical significance of CRM according to the current criteria of the Royal College of Pathologists (RCP) and the College of American Pathologists (CAP). METHODS: Patients (115) who underwent esophagectomy between 2000 and 2006 were included in this retrospective study. Factors such as neo-adjuvant therapy, site, histological type, size, and lymph node involvement were tested to determine predictability of CRM involvement. Along with these, age, sex, CRM, and adjuvant therapy were analyzed to determine influence on survival. RESULTS: On the basis of CRM, patients were divided into three groups (involved, 0.1-1 mm and >1mm). Size (T) was the only factor strongly predictive of CRM involvement (P < 0.001). Size (T; P = 0.04) and lymph node involvement (N; P = 0.0003) were found to significantly influence overall survival (OS). When patients with CRM (involved and 0.1-1mm) were compared with those with CRM > 1 mm, OS was significantly prolonged in the latter (P = 0.02). CONCLUSION: This study appears to lend credence to the RCP criteria for definition of CRM over the CAP criteria.

Reasons for the use and non-use of school sexual health services: a systematic review of young people's views.

BACKGROUND: The potential for sexual health services to influence the sexual health and behaviour of school-aged young people is only likely to be realised if these services are accessed. This review and synthesis seeks to explore children and adolescents' views and experiences of school-based and school-linked sexual health services to identify barriers to and facilitators of service use. METHODS: The study design is a systematic review of studies focusing on the views of children and adolescents (11-18 years) about relevant services. Sixteen databases were searched, titles and abstracts were screened against the inclusion criteria, data extraction and quality assessment of included studies were performed and thematic synthesis was undertaken. RESULTS: Nineteen relevant studies were identified, but only studies from the USA and the UK satisfied the inclusion criteria. The principal themes to emerge from the analysis were awareness and need, confidentiality and disclosure, perceptions of staff, service location, physical environment, costs and types of services on offer. These findings were consistent across country and type of service. CONCLUSIONS: In the view of young people, school-linked sexual health services need to guarantee and promote the ideas of privacy, confidentiality and approachability if they are to be accessed and have an impact on behaviour.

Meal-induced increases in C-reactive protein, interleukin-6 and tumour necrosis factor α are attenuated by prandial + basal insulin in patients with Type 2 diabetes.

AIM: To determine if a regimen with prandial + basal insulin compared with basal insulin attenuates post-meal inflammatory and glycative biomarkers in patients with Type 2 diabetes. METHODS: This test-meal sub-study in the USA is from a previously reported clinical trial comparing the effect on glycaemic control of 24 weeks of thrice-daily pre-meal insulin lispro mix 50 (50% insulin lispro, 50% insulin lispro protamine suspension) or bedtime insulin glargine, both plus metformin. In the sub-study, glucose, insulin, triglycerides, high-sensitivity C-reactive protein, tumour necrosis factor α, interleukin-6, methylglyoxal and 3-deoxyglucosone were measured during the post-meal period of a mixed-meal breakfast at the final visit. Prandial + basal (n = 25) and basal (n = 21) insulin were administered at the same times as during the previous 24 weeks. RESULTS: Post-meal, the prandial + basal insulin group had significantly higher insulin, lower glucose and triglycerides, as well as lower high-sensitivity C-reactive protein, tumour necrosis factor α and interleukin-6, than the basal insulin group. Glucose incremental area under the concentration curve significantly correlated with high-sensitivity C-reactive protein, tumour necrosis factor α, interleukin-6, methylglyoxal and 3-deoxyglucosone incremental area under the concentration curve. Insulin incremental area under the concentration curve correlated inversely with high-sensitivity C-reactive protein and tumour necrosis factor α incremental area under the concentration curve. However, after adjusting for glucose incremental area under the concentration curve, these inverse correlations were no longer significant. Triglyceride incremental area under the concentration curve was not correlated with any biomarker incremental area under the concentration curve. CONCLUSIONS: Controlling post-meal hyperglycaemia with prandial + basal insulin in patients with Type 2 diabetes attenuates meal-induced increases in high-sensitivity C-reactive protein, interleukin-6 and tumour necrosis factor α compared with basal insulin. The rise in post-meal glucose, but not triglycerides, significantly correlated with the rise in post-meal inflammatory and glycative biomarkers.

Nicotine stimulates angiogenesis and promotes tumor growth and atherosclerosis.

We provide anatomic and functional evidence that nicotine induces angiogenesis. We also show that nicotine accelerates the growth of tumor and atheroma in association with increased neovascularization. Nicotine increased endothelial-cell growth and tube formation in vitro, and accelerated fibrovascular growth in vivo. In a mouse model of hind-limb ischemia, nicotine increased capillary and collateral growth, and enhanced tissue perfusion. In mouse models of lung cancer and atherosclerosis, we found that nicotine enhanced lesion growth in association with an increase in lesion vascularity. These effects of nicotine were mediated through nicotinic acetylcholine receptors at nicotine concentrations that are pathophysiologically relevant. The endothelial production of nitric oxide, prostacyclin and vascular endothelial growth factor might have a role in these effects.

The development of two postnatal health instruments: one for mothers (M-PHI) and one for fathers (F-PHI) to measure health during the first year of parenting.

PURPOSE: To develop and psychometrically evaluate two questionnaires measuring both positive and negative postnatal health of mothers (M-PHI) and fathers (F-PHI) during the first year of parenting. METHODS: The M-PHI and the F-PHI were developed in four stages. Stage 1: Postnatal women's focus group (M-PHI) and postnatal fathers' postal questionnaire (F-PHI); Stage 2: Qualitative interviews; Stage 3: Pilot postal survey and main postal survey; and Stage 4: Test-retest postal survey. RESULTS: The M-PHI consisted of a 29-item core questionnaire with six main scales and five conditional scales. The F-PHI consisted of a 27-item questionnaire with six main scales. All scales achieved good internal reliability (Cronbach's α 0.66-0.87 for M-PHI, 0.72-0.90 for F-PHI). Intraclass correlation coefficients demonstrated high test-retest reliability (0.60-0.88). Correlation coefficients supported the criterion validity of the M-PHI and the F-PHI when tested against the Short-Form-12 (SF-12), Edinburgh Postnatal Depression Scale (EPDS) and the Warwick and Edinburgh Mental Well-Being Scale (WEMWBS). CONCLUSION: The M-PHI and F-PHI are valid, reliable, parent-generated instruments. These unique instruments will be invaluable for practitioners wishing to promote family-centred care and for trialists and other researchers requiring a validated instrument to measure both positive and negative health during the first postnatal year, as to date no such measurement has existed.