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In this paper, we show how the methods of systematic reviewing and meta-analysis can be used in conjunction with structural equation modeling to summarize the results of studies in a way that will facilitate the theory development and testing needed to advance prevention science. We begin with a high-level overview of the considerations that researchers need to address when using meta-analytic structural equation modeling (MASEM) and then discuss a research project that brings together theoretically important cognitive constructs related to depression to (a) show how these constructs are related, (b) test the direct and indirect effects of dysfunctional attitudes on depression, and (c) test the effects of study-level moderating variables. Our results suggest that the indirect effect of dysfunctional attitudes (via negative automatic thinking) on depression is two and a half times larger than the direct effect of dysfunctional attitudes on depression. Of the three study-level moderators tested, only sample recruitment method (clinical vs general vs mixed) yielded different patterns of results. The primary difference observed was that the dysfunctional attitudes → automatic thoughts path was less strong for clinical samples than it was for general and mixed samples. These results illustrate how MASEM can be used to compare theoretically derived models and predictions resulting in a richer understanding of both the empirical results and the theories underlying them.

Background Diet-induced obesity (DIO) and psychological stress are significant independent regulators of gastrointestinal physiology; however, our understanding of how these two disorders influence the host-microbe interface is still poorly characterized. The aim of this study was to assess the combined influences of diet-induced obesity and psychological stress on microbiome composition and colonic gene expression. Methods C57BL/6J mice (n = 48) were subject to a combination of 22 weeks of Western diet (WD) feeding and a chronic restraint stressor (CRS) for the last 4 weeks of feeding. At the end of the combined intervention, microbiome composition was determined from cecal contents, and colonic tissue gene expression was assessed by multiplex analysis using NanoString nCounter System and real-time qPCR. Results WD feeding induced a DIO phenotype with increased body weight, worsened metabolic markers, and alterations to microbiome composition. CRS reduced body weight in both dietary groups while having differential effects on glucose metabolism. CRS improved the Firmicutes/Bacteroidetes ratio in WD-fed animals while expanding the Proteobacteria phyla. Significantly lower expression of colonic Tlr4 (p = 0.008), Ocln (p = 0.004), and Cldn3 (p = 0.004) were noted in WD-fed animals compared to controls with no synergistic effects observed when combined with CRS. No changes to colonic expression of downstream inflammatory mediators were observed. Interestingly, higher levels of expression of Cldn2 (p = 0.04) and bile acid receptor Nr1h4 (p = 0.02) were seen in mice exposed to CRS. Conclusion Differential but not synergistic effects of WD and CRS were noted at the host-microbe interface suggesting multifactorial responses that require further investigation.

Current concepts of the extended amygdala posit that basolateral to central amygdala projections mediate fear‐conditioned autonomic alerting, whereas projections to the bed nucleus of the stria terminalis mediate sustained anxiety. Using diffusion tensor imaging tractography in humans, we show that microstructure of the stria terminalis correlates with an orienting bias towards threat in a saccade decision task, providing the first evidence that this circuit supports decisions guiding evaluation of threatening stimuli.

Objective Despite the move to at-home, small-volume collection kits to facilitate large population-based studies of faecal microbial compositional profiling, there remains limited reporting on potential impacts of faecal subsampling approaches on compositional profiles. This study aimed to compare the microbial composition from faecal subsamples ( Results There were no significant differences in OTU count (p = 0.32) or Shannon diversity index (p = 0.29) between the subsamples. Comparison of relative abundance for identified taxa revealed very few differences between subsamples. At the lower levels of taxonomic classification differences in abundance of the Bacillales (p = 0.02) and the Eubacteriaceae family (p = 0.03), and the Eubacterium genera (p = 0.03) were noted. The observation of consistent microbial compositional profiles between faecal subsamples from the beginning and end of a single bowel movement is an important outcome for study designs employing this approach to faecal sample collection. These findings provide assurance that use of a faecal subsample for microbial composition profiling is generally representative of the gut luminal contents more broadly.

In this paper, we show how the methods of systematic reviewing and meta-analysis can be used in conjunction with structural equation modeling to summarize the results of studies in a way that will facilitate the theory development and testing needed to advance prevention science. We begin with a high-level overview of the considerations that researchers need to address when using meta-analytic structural equation modeling (MASEM) and then discuss a research project that brings together theoretically important cognitive constructs related to depression to (a) show how these constructs are related, (b) test the direct and indirect effects of dysfunctional attitudes on depression, and (c) test the effects of study-level moderating variables. Our results suggest that the indirect effect of dysfunctional attitudes (via negative automatic thinking) on depression is two and a half times larger than the direct effect of dysfunctional attitudes on depression. Of the three study-level moderators tested, only sample recruitment method (clinical vs general vs mixed) yielded different patterns of results. The primary difference observed was that the dysfunctional attitudes → automatic thoughts path was less strong for clinical samples than it was for general and mixed samples. These results illustrate how MASEM can be used to compare theoretically derived models and predictions resulting in a richer understanding of both the empirical results and the theories underlying them.

Rodent models are important in mechanistic studies of the physiological and pathophysiological determinants of behaviour. The Open Field Test (OFT) is one of the most commonly utilised tests to assess rodent behaviour in a novel open environment. The key variables assessed in an OFT are general locomotor activity and exploratory behaviours and can be assessed manually or by automated systems. Although several automated systems exist, they are often expensive, difficult to use, or limited in the type of video that can be analysed. Here we describe a machine-learning algorithm - dubbed Cosevare - that uses a trained YOLOv3 DNN to identify and track movement of mice in the open-field arena. We validated Cosevare's capacity to accurately track locomotive and exploratory behaviour in 10 videos, comparing outputs generated by Cosevare with analysis by 5 manual scorers. Behavioural differences between control mice and those with diet-induced obesity (DIO) were also documented. We found the YOLOv3 based tracker to be accurate at identifying and tracking the mice within the open-field arena and in instances with variable backgrounds. Additionally, kinematic and spatial-based analysis demonstrated highly consistent scoring of locomotion, centre square duration (CSD) and entries (CSE) between Cosevare and manual scorers. Automated analysis was also able to distinguish behavioural differences between healthy control and DIO mice. The study found that a YOLOv3 based tracker is able to easily track mouse behaviour in the open field arena and supports machine learning as a potential future alternative for the assessment of animal behaviour in a wide range of species in differing environments and behavioural tests.

OnBehalf United Kingdom Cardiac SABR consortium Background Stereotactic Ablative Body Radiotherapy (SABR) is a novel non-invasive treatment for Ventricular Tachycardia (VT) refractory to standard catheter ablation. 3 UK hospitals have started compassionate use cardiac SABR programmes, and are working in close collaboration. Purpose To report initial UK experience for treatment of refractory VT with cardiac SABR. Methods All patients had undergone prior unsuccessful invasive ablation with VT recurrence despite anti-arrhythmic drug (AAD) use. High-resolution CT imaging with 3D reconstruction was combined with 12 lead ECGs of VT and prior invasive +/- non-invasive electrophysiology mapping data to define a cardiac target. Treatment margins were modified to account for cardiac/respiratory motion and to minimise off target treatment to other organs as per clinical SABR practice. Single fraction high dose treatment (20-25 Gy) was delivered by CT guided Linear Accelerator. Patients were assessed regularly with clinical review and remote device monitoring. Results 3 patients have been treated so far with aetiologies of prior myocarditis, non-ischaemic dilated cardiomyopathy and ischaemic cardiomyopathy. All patients successfully received planned SABR treatment in Conclusions Cardiac SABR shows promise for VT control, but further experience and trials are needed. Integration of imaging and electrophysiology data to generate accurate targets appears critical. The effect of SABR seems to develop over several weeks after therapy. Patient selection and timing of SABR delivery is important with acknowledgement that competing causes of death exist in patients with refractory VT entering a compassionate use program. Abstract Figure. Example SBRT plan

Background\ud Postmastectomy radiotherapy in patients with four or more positive axillary nodes reduces breast cancer mortality, but its role in patients with one to three involved nodes is controversial. We assessed the effects of postmastectomy radiotherapy on quality of life (QOL) in women with intermediate-risk breast cancer.\ud \ud Methods\ud SUPREMO is an open-label, international, parallel-group, randomised, controlled trial. Women aged 18 years or older with intermediate-risk breast cancer (defined as pT1–2N1; pT3N0; or pT2N0 if also grade III or with lymphovascular invasion) who had undergone mastectomy and, if node positive, axillary surgery, were randomly assigned (1:1) to receive chest wall radiotherapy (50 Gy in 25 fractions or a radiobiologically equivalent dose of 45 Gy in 20 fractions or 40 Gy in 15 fractions) or no radiotherapy. Randomisation was done with permuted blocks of varying block length, and stratified by centre, without masking of patients or investigators. The primary endpoint is 10-year overall survival. Here, we present 2-year results of QOL (a prespecified secondary endpoint). The QOL substudy, open to all UK patients, consists of questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23, Body Image Scale, Hospital Anxiety and Depression Scale [HADS], and EQ-5D-3L) completed before randomisation, and at 1, 2, 5, and 10 years. The prespecified primary outcomes within this QOL substudy were global QOL, fatigue, physical function, chest wall symptoms, shoulder and arm symptoms, body image, and anxiety and depression. Data were analysed by intention to treat, using repeated mixed-effects methods. This trial is registered with the ISRCTN registry, number ISRCTN61145589.\ud \ud Findings\ud Between Aug 4, 2006, and April 29, 2013, 1688 patients were enrolled internationally and randomly assigned to receive chest wall radiotherapy (n=853) or not (n=835). 989 (79%) of 1258 patients from 111 UK centres consented to participate in the QOL substudy (487 in the radiotherapy group and 502 in the no radiotherapy group), of whom 947 (96%) returned the baseline questionnaires and were included in the analysis (radiotherapy, n=471; no radiotherapy, n=476). At up to 2 years, chest wall symptoms were worse in the radiotherapy group than in the no radiotherapy group (mean score 14·1 [SD 15·8] in the radiotherapy group vs 11·6 [14·6] in the no radiotherapy group; effect estimate 2·17, 95% CI 0·40–3·94; p=0·016); however, there was an improvement in both groups between years 1 and 2 (visit effect −1·34, 95% CI −2·36 to −0·31; p=0·010). No differences were seen between treatment groups in arm and shoulder symptoms, body image, fatigue, overall QOL, physical function, or anxiety or depression scores.\ud \ud Interpretation\ud Postmastectomy radiotherapy led to more local (chest wall) symptoms up to 2 years postrandomisation compared with no radiotherapy, but the difference between groups was small. These data will inform shared decision making while we await survival (trial primary endpoint) results.\ud \ud Funding\ud Medical Research Council, European Organisation for Research and Treatment of Cancer, Cancer Australia, Dutch Cancer Society, Trustees of Hong Kong and Shanghai Banking Corporation.

Objectives Parental knowledge on sleep hygiene in children may be a contributing factor for sleep difficulties in preschoolers. As sleep is crucial for healthy development, it is important to understand how parental knowledge can be improved. The aim of this qualitative study was to develop an understanding of advice available in the United Kingdom (UK) on sleep in young children. Design This study employed constructivist grounded theory methodology. Methods Participants were recruited via social media and a previously constructed participant database. Interviews were audio-recorded, transcribed, and analysed. Results Fourteen mothers were interviewed independently, whilst one mother was interviewed together with her husband. Themes relating to how UK mothers wish advice on sleep to be formulated, what they believe it should include and when they would like to receive it, were identified from the data. Specifically, this study suggests that UK mothers value experience and thus recommends that advice be made through collaboration projects involving both professionals and parents. It also suggests that advice should be readily available and given to expecting parents prior to the arrival of their baby as well as at regular follow-ups. In addition, the participating mothers wanted advice to be balanced and non-judgemental. Conclusion This study looks at the views of mainly White British mothers currently residing within the United Kingdom. Thus, it may not represent the views of everyone in the United Kingdom. Nevertheless, it still makes important recommendations for practice. For example, relationships between health professionals and parents need to be improved and information on different sleeping practices widely dispersed. Statement of contribution What is already known on this subject? Poor sleep is common in young children. Young children's sleep quality can be affected by parental behaviours. Parents lack knowledge of sleep in young children. What does this study add? According to this study: It would be beneficial for professionals to work in partnership with parents when formulating advice. Mothers want advice to appreciate individual differences, be free of stigma, and manage expectations. Mothers want advice both prenatally and throughout their child's development.

INTRODUCTION In the North Trent Cancer Network (NTCN) patients requiring retroperitoneal lymphadenectomy for metastatic testicular cancer have been treated by vascular service since 1990. This paper reviews our experience and considers the case for involvement of vascular surgeons in the management of these tumours. PATIENTS AND METHODS Patients referred by the NTCN to the vascular service for retroperitoneal lymphadenectomy between 1990 and 2009 were identified through a germ cell database. Data were supplemented by a review of case notes to record histology, intraoperative and postoperative details. RESULTS A total of 64 patients were referred to the vascular service for retroperitoneal lymph node dissection, with a median age of 29 years (16–63 years) and a median follow-up of 4.9 years. Ten patients died: eight from tumour recurrence, one from septicaemia during chemotherapy and one by suicide. Of the 54 who survived, 7 were alive with residual masses and 47 patients were disease-free at the last follow-up. Sixteen patients required vascular procedures: four had aortic repair (fascia), three had aortic replacement (spiral graft), four had inferior vena cava resection, two had iliac artery replacement and two had iliac vein resection. CONCLUSIONS Retroperitoneal lymph node dissection often involves mobilisation and/or the resection/replacement of major vessels. We recommend that a vascular surgeon should be a part of testicular germ cell multidisciplinary team.

The relationship between aquaculture and infestations of sea lice on wild sea trout ( Salmo trutta ) populations is controversial. Although some authors have concluded that there is a link between aquaculture and lice burdens on wild fish, others have questioned this interpretation. Lice levels have been shown to be generally higher on Atlantic salmon farms during the second years of two-year production cycles. Here we investigate whether this pattern relates to lice burdens on wild fish across broad temporal and spatial axes. Within Loch Shieldaig across five successive farm cycles from 2000 to 2009, the percentage of sea trout with lice, and those above a critical level, were significantly higher in the second year of a two-year production cycle. These patterns were mirrored in 2002–2003 across the Scottish west coast. The results suggest a link between Atlantic salmon farms and sea lice burdens on sea trout in the west of Scotland.

The liquefaction potential of clean and silty sands is examined on the basis of the field measurement of the shear-wave velocity, Vs. The starting point is the database of 225 case histories supporting the Andrus-Stokoe Vs-based liquefaction chart for sands, silts, and gravels. Only clean and silty sands with nonplastic fines are considered, resulting in a reduced database of 110 case histories, which are plotted separately by type of deposit. A line of constant cyclic shear strain, γcl≈0.03%, is recommended for liquefaction evaluation of recent uncompacted clean and silty sand fills and earthquake magnitude, Mw=7.5. The geologically recent natural silty sand sites in the Imperial Valley of southern California have significantly higher liquefaction resistance as a result of preshaking caused by the high seismic activity in the valley. A line of constant cyclic shear strain, γcl≈0.1–0.2%, is recommended for practical use in the Imperial Valley. Additional research including revisiting available Vs-...

Doctors are at an increased risk for prescription drug use, particularly opioids and benzodiazpines. This use can interfere with work function and has major potential negative implications for patient safety. Oral naltrexone, an opioid antagonist, has been used as part of a management strategy for opioid-dependent physicians. While some patients stabilize on oral naltrexone, others relapse to opioid use. An alternative method of naltrexone maintenance involves the injection or surgical insertion of a sustained release preparation of naltrexone. This approach dramatically improves compliance, removing the onus from the previously opioid impaired physician to use daily oral naltrexone. This article describes the cases of four opioid-impaired doctors who received naltrexone (either oral or implant) as part of their management. The authors conclude that monitoring daily oral naltrexone use and detecting early opioid relapse is difficult, placing both the opioid impaired physician and their patients at risk. In contrast, by using implantable naltrexone, compliance is assured and opioid abstinence can virtually be guaranteed for five months. It is argued that naltrexone implants offer a level of protection not achieved with any previous treatment. It is recommended that management should involve early and close collaboration between the treating doctor and the Medical Board, with initial treatment, ongoing monitoring and follow-up being a Medical Board requirement for registration.

Patients with an isolated spiral or long oblique fracture of the proximal phalanx were randomized into two groups. One was treated by closed reduction and Kirschner wire fixation and the second treated by open reduction and lag screw fixation. An independent observer assessed function, pain, movement, grip strength and intrinsic muscle function. X-rays were assessed for malunion. Thirty-two patients were entered the study and 15 in the Kirschner wire and 13 in the lag screw group were reviewed at a mean follow-up of 40 months. There was no significant difference in the functional recovery rates or in the pain scores for the two groups. X-rays showed similar rates of malunion and there were no statistically significant differences in range of movement or grip strength.

The synthesis and characterisation of the mercury(II) complexes [RHg{(SePiPr2)2N}] [R = methyl (2a), ethyl (3a), thienyl (T) (4a), 2-selenyl (SL) (5a) and phenyl (6a)], prepared by the reaction of the sodium salt of NH(SePiPr2)2 (1a) with the appropriate alkyl/aryl mercury halide in methanol are reported. Results are compared and contrasted to the corresponding sulfur analogues [RHg{(SPiPr2)2N}] [R = T (4b), SL (5b) and Ph (6b)], and these new compounds have been evaluated, by thermogravimetric analysis and mass spectrometry as potential precursors and powder X-ray diffraction used to identify solid-state products. The solid-state structure of the symmetrical complex Hg[(SePiPr2)2N]27a, and di(2-selenyl)mercury, one of the symmetrisation products of [SLHg{(SePiPr2)2N}] 5a in solution, have been determined by single crystal X-ray crystallography.

Background TNT previously reported that patients(pts) with advanced triple negative breast cancer(TNBC) and germline BRCA1/2(gBRCA+) mutations are more likely to respond to carboplatin(C) than to docetaxel(D), and have longer progression-free survival with C. Here, we report results from a pre-planned biological analysis to test whether BRCA silencing or methylation status confer sensitivity to platinum. Methods Pts eligible for TNT had ER-, PgR-, HER2- BC or were known gBRCA+(any ER/PgR/HER2). Pts were randomized to C(AUC 6 q3wk) or D(100mg/m2 q3wk) for 6-8 cycles or until disease progression if sooner, with crossover possible on progression. Blood and archival tissue samples were requested for BRCA1/2 genotyping, central analysis of TN and DNA repair deficiency biomarkers. Primary endpoint was intention-to-treat objective response rate(ORR) up to cycle 6. BRCA1 mRNA level was estimated from whole-genome total RNA sequencing(RNA-Seq). BRCA1 methylation analysis was quantified by bisulfite sequencing. A methylation score for the sample was computed as percentage of methylated reads relative to total number of reads that were either methylated or not methylated for CpG sites. A sample with a score >10% was considered methylated(BRCA1meth)? a BRCA1 mRNA level "silenced" subgroup(BRCA1 silencing) was defined as value of log2(mRNA) Results 212 and 191 pts' samples were assessed for BRCA1 methylation and mRNA levels. 33 pts (15.6%) were found to be BRCA1meth. Pts with BRCA1meth had a better response to D (42%, 95%CI: 20, 64) than C (21%, 95%CI: -0.1, 43)? absolute difference (C-D) -21% (95%CI: -52, 10)? p=0.28), but not statistically significant. There was no evidence of a difference when gBRCA+ tumours were excluded. 31 pts (16%) had BRCA1 silencing. Concordant with BRCA1meth, pts with BRCA1 silencing had a better response to D (65%, 95%CI: 42, 87) than C (29%, 95%CI: 4.9, 52)? absolute difference (C-D) -36% (95%CI: -69, -3.3)? p=0.07), with an odds ratio 0.22 (95%CI: 0.035, 1.2) in favor of D, interaction with treatment not significant (p=0.066). 19 pts with BRCA1meth and BRCA1 silencing had a better response to D (60%, 95%CI: 30, 90) than C (22%, 95%CI: -5.0, 49)? absolute difference (C-D) -38% (95%CI: -79, 2.9) in favor of D (p=0.17), and the interaction was not significant (p=0.15). Further exploratory analyses examining any relationship between a response to C and new cutpoints for BRCA1meth or BRCA1 mRNA level did not suggest any evidence of a signal. Conclusion Our data did not support a priori hypotheses that BRCA1 methylation or silencing would be associated with a greater response to C than D, which is consistent with other reports in ovarian cancer. As BRCA1 methylation will not always lead to significant silencing or be the only cause of low BRCA1 gene expression, exploratory analysis is investigating the interaction of BRCA silenced group with D sensitivity. RNA-seq is ongoing and results from the final database will be presented. Citation Format: Tutt A, Cheang MCU, Kilburn L, Tovey H, Gillett C, Pinder S, Lanchbury J, Abraham J, Barrett S, Barrett-Lee P, Chan S, Gazinska P, Grigoriadis A, Kernaghan S, Hoadley K, Gutin A, Harper-Wynne C, Hatton M, Owen J, Parker P, Roylance R, Shaw A, Smith I, Thompson R, Timms K, Wardley A, Wilson G, Harries M, Ellis P, Ashworth A, Perou C, Bliss J, Rahman N, Brown R, On Behalf of the TNT Trial Management Group and Investigators. BRCA1 methylation status, silencing and treatment effect in the TNT trial: A randomized phase III trial of carboplatin compared with docetaxel for patients with metastatic or recurrent locally advanced triple negative or BRCA1/2 breast cancer (CRUK/07/012) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr S6-01.

Is handedness related to anxiety? Two separable dimensions of handedness have been considered in previous studies: Direction of the preferred hand (left or right) and the consistency with which the preferred hand is used over the nonpreferred hand (consistent or inconsistent). Findings have included (1) left-handedness being associated with greater anxiety than right-handedness, (2) consistent-handedness being associated with greater anxiety than inconsistent-handedness and (3) neither dimension being associated with anxiety. Here, we administered measures of trait anxiety, state anxiety and worry to individuals classified as consistent-left, inconsistent-left, inconsistent-right or consistent-right. Neither direction nor consistency had a main effect on any measure. However, there was a direction by consistency interaction in trait and state anxiety measured on the State/Trait Anxiety Inventory. Among right-handers, inconsistent individuals reported less anxiety than consistent individuals. Among left-handers, consistency was unrelated to anxiety. In consequence of this pattern, inconsistent right-handers were less anxious than inconsistent left-handers. Hence, supporting prior studies, left-handedness was associated with greater anxiety than right-handedness (but only among inconsistent individuals) and consistency was associated with greater anxiety than inconsistency (but only among right-handers). These findings advance our understanding of handedness consistency as an important individual difference factor in personality and cognition.

Sir, The review of 22 cases of septic discitis1 highlights similarities with other deep‐seated infections within the musculoskeletal system such as septic arthritis (SA). Here we present a case of septic discitis that confirms these similarities, shows that ultrasound can be useful in identifying soft tissue damage and demonstrates that distant infection can be the site of haematogenous bacterial spread. It also shows that the C‐reactive protein (CRP) is particularly useful in monitoring the acute phase response and success of treatment. A 43‐year‐old fireman was admitted with acute‐onset lower back and left hip pain. Five weeks earlier, he had sustained a scalp laceration necessitating suture and intravenous antibiotic treatment. Subsequently, a swelling developed at the site of injection (dorsum of the right hand) and he became unable to elevate the middle and ring fingers, but did not seek further medical advice at that time. Two weeks before admission, he developed increasing neck pain and difficulty moving the right shoulder that was compounded by increasing pain and stiffness of the lower back and left hip. This had deteriorated over the preceding 72 h, and had limited weight‐bearing, even though he had lost over 2 stone (14 kg) in weight. Two days before presentation, the left knee and ankle became stiff and he noticed a painless swelling over the right elbow. He denied rigors or sweats during this time and had only noted an occasional fever. There was no history of inflammatory joint disease, and other than treated hypertension, obesity and previous excessive alcohol consumption, the patient had no other relevant history. On examination he was apyrexial, and remained so for 24 h. The swelling of the dorsum of the right hand …

Fifty-seven values for the ortho-benzylic coupling constant 4JMeCCH (henceforth denoted as 4JOB) were obtained for a variety of heteroaromatic systems. It was shown that a good correlation exists between 4JOB when the methyl group is not α to the heteroatom and the SCF-MO bond order. This method can therefore be used as an experimental means of determining bond orders in heteroaromatic systems. An examination of bond alternation in thirteen heteroaromatic systems has given a measure of relative “degree of aromaticity” for a larger number of systems than previously reported by any single method.

Fifty-seven values for the ortho-benzylic coupling constant 4JMeCCH (henceforth denoted as 4JOB) were obtained for a variety of heteroaromatic systems. It was shown that a good correlation exists between 4JOB when the methyl group is not α to the heteroatom and the SCF-MO bond order. This method can therefore be used as an experimental means of determining bond orders in heteroaromatic systems. An examination of bond alternation in thirteen heteroaromatic systems has given a measure of relative “degree of aromaticity” for a larger number of systems than previously reported by any single method.

Introduction NIV is a treatment for acute respiratory acidosis in patients admitted with exacerbations of COPD. BTS audits have demonstrated that NIV is frequently used for other conditions, functional dependency is common and in-hospital mortality is high. Tools to prognosticate outcome from acute use of NIV tend to be disease-specific. Targeting the use of NIV to those who are most likely to benefit from it should be a clinical and ethical priority. Frailty relates to patient outcome in clinical settings including elderly patients with COPD and critical care admissions. We hypothesised that patients with higher frailty scores who receive NIV for acute respiratory failure have inferior outcomes, compared to those assessed as being less frail. Methods Prospective study of patients receiving acute NIV for respiratory failure; over 15 months. The respiratory physiotherapists manage all such patients and collect data into the EPR. An additional item of data was collected – the Clinical Frailty Scale (CFS). All analyses were by episode apart from demographics and mortality which were by individual. Results 89 patients received 110 episodes of acute NIV, median age 79, (range 23–97) years. Diagnoses: COPD (56%), Pneumonia and ‘other’ (30%), cardiogenic pulmonary oedema (4%), obesity-related (4%), chest wall/neuromuscular (7%). At initiation of NIV: median pH 7.26, PaCO2 9.8 kPa, PaO2 8.5 kPa. Duration of hospital stay, median 16.5 days, in-hospital mortality (28%). CFS median score 6, range (2–8). There was no correlation between CFS and age. CFS was statistically significantly higher in those who died (either during their index admission or during follow-up) than in those who survived – see Figure 1. Patients with a CFS of 7 or 8 had an in-hospital mortality of 40% and a total mortality of 80%. By contrast those with a CFS of less than 7 had an in-hospital mortality of 24% and a total mortality of 46%. Conclusions Patients receiving acute NIV who are very frail (CFS 7 or 8) are less likely to experience a mortality benefit. These data should inform discussions and decision-making about use of NIV.

To describe from a population-based perspective, recent and temporal (1975-1995) trends in the incidence, in-hospital and postdischarge case-fatality rates of heart failure (HF) complicating acute myocardial infarction (AMI).Extremely limited data are available describing the incidence and case-fatality rates associated with HF complicating AMI from a community-wide perspective.The medical records of 6,798 residents of the Worcester, Massachusetts metropolitan area with validated MI and without previous HF hospitalized in 10 annual periods between 1975 and 1995 were reviewed.The proportion of AMI patients developing HF during hospitalization declined between 1975-1978 (38%) and 1993-1995 (33%) (p0.001). After controlling for potentially confounding factors, the risk of developing HF declined progressively, albeit modestly, over time. In-hospital case-fatality rates of patients with AMI complicated by HF declined by approximately 46% between 1975-1978 (33%) and 1993-1995 (18%) (p0.001). Improving trends in hospital survival were observed after adjusting for potentially confounding prognostic factors. The one-year post-discharge mortality rate for hospital survivors of HF did not change over the 20-year period under study, even after controlling for additional prognostic characteristics.The results of this community-wide study suggest encouraging declines in the incidence and hospital death rates associated with HF complicating AMI. Continued efforts need to be directed towards the prevention of HF given the magnitude of this clinical syndrome. Efforts of secondary prevention are needed to identify and improve the treatment of patients with symptomatic left ventricular dysfunction following AMI given the lack of improvement in the long-term prognosis of these patients.

A fundamental step towards any potential integration of the specialties of medical and clinical oncology into a common faculty in the UK, is to establish a core curriculum of training in both cancer sciences and clinical cancer medicine for both specialties. A questionnaire was sent to all UK trainees in cancer medicine in March 1997 to establish a baseline of patterns of training and to gather information on the trainees' views regarding the future of oncology training. The results of this survey are presented along with suggestions for discussion on the future of oncology training.

This study was initiated by the Society for Vascular Nursing (SVN) Research Committee for the purpose of establishing priorities in vascular nursing research. With a three-round Delphi technique for this study, 176 SVN members were asked the question: What are the most significant problems or questions affecting the welfare of patients with vascular disease that can be solved or answered through nursing research? In round I, experts in vascular nursing ( n =43) identified 182 items that were edited by the investigators into 135 researchable questions and 15 categories. In round II, the expert panel ( n =35) rated each item on a 1 to 7-point scale regarding impact on patient welfare. For round III, panelists ( n =34) were asked to rerate each item, taking into consideration their individual and group mean on each item. Participants who responded to all three rounds were generally expertenced advanced practice vascular nurses. The number one research priority identified by this panel was the following: What are the most important barriers to compliance with treatment regimens (diet, cessation of smoking, etc) in the patient with vascular disease? Other top research priorities were concerned with nursing standards, patient education, risk factor modification, pain management, decreasing length of stay, nursing education, stress and anxiety in the preoperative period, and providing care at less expense. The research priorities identified by this study are intended to provide direction for the SVN and its members in their efforts to foster future research in vascular nursing.

The previously established n.m.r. method for estimating mobile bond orders was applied to the investigation of ground-state polarization of benzene derivatives with ortho or para pairs of +R/-R substituents, naphthalene and five heteroaromatic systems (furan, thiophen, pyrrole, quinoline and pyrazole). Evidence for significant ground-state polarization which is solvent-independent was found in a number of these systems, especially benzene, pyrrole and pyrazole.

The magnitude of the 4J proton-proton coupling constant across the fragment CH3CCH (a probe of the bond order between the central sp2-sp2 hybridized carbon atoms) has been found to be essentially independent of substitution on a toluene fragment and on the size of the ring containing the ortho-allylic fragment. The coupling constant is sensitive to direct substitution on the ortho-allylic fragment, especially where the substituent is placed α to the methyl group.