Measurement of the ν_{e}-Nucleus Charged-Current Double-Differential Cross Section at ⟨E_{ν}⟩=2.4 GeV Using NOvA.

The inclusive electron neutrino charged-current cross section is measured in the NOvA near detector using 8.02×10^{20} protons-on-target in the NuMI beam. The sample of GeV electron neutrino interactions is the largest analyzed to date and is limited by ≃17% systematic rather than the ≃7.4% statistical uncertainties. The double-differential cross section in final-state electron energy and angle is presented for the first time, together with the single-differential dependence on Q^{2} (squared four-momentum transfer) and energy, in the range 1 GeV≤E_{ν}<6 GeV. Detailed comparisons are made to the predictions of the GENIE, GiBUU, NEUT, and NuWro neutrino event generators. The data do not strongly favor a model over the others consistently across all three cross sections measured, though some models have especially good or poor agreement in the single differential cross section vs Q^{2}.

Search for Active-Sterile Antineutrino Mixing Using Neutral-Current Interactions with the NOvA Experiment.

This Letter reports results from the first long-baseline search for sterile antineutrinos mixing in an accelerator-based antineutrino-dominated beam. The rate of neutral-current interactions in the two NOvA detectors, at distances of 1 and 810 km from the beam source, is analyzed using an exposure of 12.51×10^{20} protons-on-target from the NuMI beam at Fermilab running in antineutrino mode. A total of 121 of neutral-current candidates are observed at the far detector, compared to a prediction of 122±11(stat.)±15(syst.) assuming mixing only between three active flavors. No evidence for ν[over ¯]_{µ}→ν[over ¯]_{s} oscillation is observed. Interpreting this result within a 3+1 model, constraints are placed on the mixing angles θ_{24}<25° and θ_{34}<32° at the 90% C.L. for 0.05 eV^{2}≤Δm_{41}^{2}≤0.5 eV^{2}, the range of mass splittings that produces no significant oscillations at the near detector. These are the first 3+1 confidence limits set using long-baseline accelerator antineutrinos.

Asthma and high-intensity interval training have no effect on clustered cardiometabolic risk or arterial stiffness in adolescents.

PURPOSE: Cardiometabolic risk, including arterial stiffness, is increasing in youth. Those with asthma are suggested to be particularly at risk of cardiovascular disease. Efficient and effective strategies are required to prevent the atherosclerotic process in youth. The purpose of this study was to investigate the effect of 6 months high-intensity interval training (HIIT) on cardiometabolic risk in youth with and without asthma. METHODS: 65 adolescents (31 mild asthma; 34 non-asthma) were recruited, 32 (16 asthma) of whom were randomly allocated to receive HIIT three times per week for 6 months. At baseline, mid-intervention, post-intervention and at a 3-month follow-up, anthropometric, metabolic and vascular determinants of cardiometabolic risk were assessed. Following principal component analysis (PCA), linear mixed models were used to assess the influence of asthma, HIIT and their interaction. RESULTS: Seven factors were identified which explained 88% of the common variance shared among the parameters. Those with asthma demonstrated lower arterial stiffness factor scores mid-intervention (P = 0.047) and lower cholesterol factor scores post-intervention (P = 0.022) but there was no effect of the intervention, or interaction effects, on any PCA-identified factor, at any time-point. HIIT was associated with a lower low-density lipoprotein and diastolic blood pressure at mid-intervention. DISCUSSION: Neither arterial stiffness nor clustered cardiometabolic risk are influenced by HIIT in adolescents with or without asthma, despite important changes in blood lipid and pressure profiles. Blood pressure, augmentation and pulse wave velocity should be considered physiologically distinct constructs and as potential markers of cardiovascular health.

A combined analysis of genetically correlated traits identifies 187 loci and a role for neurogenesis and myelination in intelligence.

Intelligence, or general cognitive function, is phenotypically and genetically correlated with many traits, including a wide range of physical, and mental health variables. Education is strongly genetically correlated with intelligence (rg = 0.70). We used these findings as foundations for our use of a novel approach-multi-trait analysis of genome-wide association studies (MTAG; Turley et al. 2017)-to combine two large genome-wide association studies (GWASs) of education and intelligence, increasing statistical power and resulting in the largest GWAS of intelligence yet reported. Our study had four goals: first, to facilitate the discovery of new genetic loci associated with intelligence; second, to add to our understanding of the biology of intelligence differences; third, to examine whether combining genetically correlated traits in this way produces results consistent with the primary phenotype of intelligence; and, finally, to test how well this new meta-analytic data sample on intelligence predicts phenotypic intelligence in an independent sample. By combining datasets using MTAG, our functional sample size increased from 199,242 participants to 248,482. We found 187 independent loci associated with intelligence, implicating 538 genes, using both SNP-based and gene-based GWAS. We found evidence that neurogenesis and myelination-as well as genes expressed in the synapse, and those involved in the regulation of the nervous system-may explain some of the biological differences in intelligence. The results of our combined analysis demonstrated the same pattern of genetic correlations as those from previous GWASs of intelligence, providing support for the meta-analysis of these genetically-related phenotypes.

Associations between caries levels and BMI measures among five-year-old children. Analysis and cross-sectional multi-variable analysis at individual child level.

OBJECTIVES: To establish the existence and directions of any associations between measures of body mass index (BMI) with caries levels using individual measures of each as derived from national surveys in England. METHODS: The BMIs of five-year-old children calculated from the 2017 National Child Measurement Programme and caries measures from the 2016-17 Public Health England (PHE) National dental epidemiology survey were securely linked at a child level. Comparison at individual level of caries levels and BMI z scores was done using multivariable regression. RESULTS: Records for 67,033 children were linked and allocated a deprivation quintile. An association between BMI Z score categories and caries levels was established. Caries prevalence was higher among overweight (24.4%) and very overweight (27.6%) children compared with those of average BMI (22.5%). Odds ratios were statistically significant at 1.08 and 1.14 for prevalence among overweight and very overweight children. Children of low BMI were found to have higher caries severity (1.2 d3mft) and extent (4.4 d3mft among those with any caries) compared to children of healthy BMI (0.7 d3mft, 3.3 d3mft) with statistically significant Incidence Rate Ratio of 1.24. Underweight children were more likely to have caries experience and more severe attack compared with children of healthy weight. Deprivation and ethnicity were confounding factors. CONCLUSIONS: There is some association between child BMI status and caries levels whereby caries prevalence among children of higher BMI is increased. The associations are over and above those of deprivation, ethnicity and water fluoridation individually, but these factors impact on the strength of the link between BMI and caries.

Low prevalence of male microchimerism in women with Mayer-Rokitansky-Küster-Hauser syndrome.

STUDY QUESTION: Is there an increased prevalence of male microchimerism in women with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, as evidence of fetal exposure to blood and anti-Müllerian hormone (AMH) from a (vanished) male co-twin resulting in regression of the Müllerian duct derivatives? SUMMARY ANSWER: Predominant absence of male microchimerism in adult women with MRKH syndrome does not support our hypothesis that intrauterine blood exchange with a (vanished) male co-twin is the pathophysiological mechanism. WHAT IS KNOWN ALREADY: The etiology of MRKH is unclear. Research on the phenotype analogous condition in cattle (freemartinism) has yielded the hypothesis that Müllerian duct development is inhibited by exposure to AMH in utero. In cattle, the male co-twin has been identified as the source for AMH, which is transferred via placental blood exchange. In human twins, a similar exchange of cellular material has been documented by detection of chimerism, but it is unknown whether this has clinical consequences. STUDY DESIGN, SIZE, DURATION: An observational case-control study was performed to compare the presence of male microchimerism in women with MRKH syndrome and control women. Through recruitment via the Dutch patients' association of women with MRKH (comprising 300 members who were informed by email or regular mail), we enrolled 96 patients between January 2017 and July 2017. The control group consisted of 100 women who reported never having been pregnant. PARTICIPANTS/MATERIALS, SETTING, METHODS: After written informed consent, peripheral blood samples were obtained by venipuncture, and genomic DNA was extracted. Male microchimerism was detected by Y-chromosome-specific real-time quantitative PCR, with use of DYS14 marker. Possible other sources for microchimerism, for example older brothers, were evaluated using questionnaire data. MAIN RESULTS AND THE ROLE OF CHANCE: The final analysis included 194 women: 95 women with MRKH syndrome with a mean age of 40.9 years and 99 control women with a mean age of 30.2 years. In total, 54 women (56.8%) were identified as having typical MRKH syndrome, and 41 women (43.2%) were identified as having atypical MRKH syndrome (when extra-genital malformations were present). The prevalence of male microchimerism was significantly higher in the control group than in the MRKH group (17.2% versus 5.3%, P = 0.009). After correcting for age, women in the control group were 5.8 times more likely to have male microchimerism (odds ratio 5.84 (CI 1.59-21.47), P = 0.008). The mean concentration of male microchimerism in the positive samples was 56.0 male genome equivalent per 1 000 000 cells. The prevalence of male microchimerism was similar in women with typical MRKH syndrome and atypical MRKH syndrome (5.6% versus 4.9%, P = 0.884). There were no differences between women with or without microchimerism in occurrence of alternative sources of XY cells, such as older brothers, previous blood transfusion, or history of sexual intercourse. LIMITATIONS, REASON FOR CAUTION: We are not able to draw definitive conclusions regarding the occurrence of AMH exchange during embryologic development in women with MRKH syndrome. Our subject population includes all adult women and therefore is reliant on long-term prevalence of microchimerism. Moreover, we have only tested blood, and, theoretically, the cells may have grafted anywhere in the body during development. It must also be considered that the exchange of AMH may occur without the transfusion of XY cells and therefore cannot be discovered by chimerism detection. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to test the theory that freemartinism causes the MRKH syndrome in humans. The study aimed to test the presence of male microchimerism in women with MRKH syndrome as a reflection of early fetal exposure to blood and AMH from a male (vanished) co-twin. We found that male microchimerism was only present in 5.3% of the women with MRKH syndrome, a significantly lower percentage than in the control group (17.2%). Our results do not provide evidence for an increased male microchimerism in adult women with MRKH as a product of intrauterine blood exchange. However, the significant difference in favor of the control group is of interest to the ongoing discussion on microchimeric cell transfer and the possible sources of XY cells. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: Dutch trial register, NTR5961.

First measurement of neutrino oscillation parameters using neutrinos and antineutrinos by NOvA.

The NOvA experiment has seen a 4.4σ signal of ν[over ¯]_{e} appearance in a 2 GeV ν[over ¯]_{µ} beam at a distance of 810 km. Using 12.33×10^{20} protons on target delivered to the Fermilab NuMI neutrino beamline, the experiment recorded 27 ν[over ¯]_{µ}→ν[over ¯]_{e} candidates with a background of 10.3 and 102 ν[over ¯]_{µ}→ν[over ¯]_{µ} candidates. This new antineutrino data are combined with neutrino data to measure the parameters |Δm_{32}^{2}|=2.48_{-0.06}^{+0.11}×10^{-3} eV^{2}/c^{4} and sin^{2}θ_{23} in the ranges from (0.53-0.60) and (0.45-0.48) in the normal neutrino mass hierarchy. The data exclude most values near δ_{CP}=π/2 for the inverted mass hierarchy by more than 3σ and favor the normal neutrino mass hierarchy by 1.9σ and θ_{23} values in the upper octant by 1.6σ.

Genetic contributions to self-reported tiredness.

Self-reported tiredness and low energy, often called fatigue, are associated with poorer physical and mental health. Twin studies have indicated that this has a heritability between 6 and 50%. In the UK Biobank sample (N=108 976), we carried out a genome-wide association study (GWAS) of responses to the question, 'Over the last two weeks, how often have you felt tired or had little energy?' Univariate GCTA-GREML found that the proportion of variance explained by all common single-nucleotide polymorphisms for this tiredness question was 8.4% (s.e.=0.6%). GWAS identified one genome-wide significant hit (Affymetrix id 1:64178756_C_T; P=1.36 × 10-11). Linkage disequilibrium score regression and polygenic profile score analyses were used to test for shared genetic aetiology between tiredness and up to 29 physical and mental health traits from GWAS consortia. Significant genetic correlations were identified between tiredness and body mass index (BMI), C-reactive protein, high-density lipoprotein (HDL) cholesterol, forced expiratory volume, grip strength, HbA1c, longevity, obesity, self-rated health, smoking status, triglycerides, type 2 diabetes, waist-hip ratio, attention deficit hyperactivity disorder, bipolar disorder, major depressive disorder, neuroticism, schizophrenia and verbal-numerical reasoning (absolute rg effect sizes between 0.02 and 0.78). Significant associations were identified between tiredness phenotypic scores and polygenic profile scores for BMI, HDL cholesterol, low-density lipoprotein cholesterol, coronary artery disease, C-reactive protein, HbA1c, height, obesity, smoking status, triglycerides, type 2 diabetes, waist-hip ratio, childhood cognitive ability, neuroticism, bipolar disorder, major depressive disorder and schizophrenia (standardised ß's had absolute values<0.03). These results suggest that tiredness is a partly heritable, heterogeneous and complex phenomenon that is phenotypically and genetically associated with affective, cognitive, personality and physiological processes.

Genetic contributions to Trail Making Test performance in UK Biobank.

The Trail Making Test (TMT) is a widely used test of executive function and has been thought to be strongly associated with general cognitive function. We examined the genetic architecture of the TMT and its shared genetic aetiology with other tests of cognitive function in 23 821 participants from UK Biobank. The single-nucleotide polymorphism-based heritability estimates for trail-making measures were 7.9% (part A), 22.4% (part B) and 17.6% (part B-part A). Significant genetic correlations were identified between trail-making measures and verbal-numerical reasoning (rg>0.6), general cognitive function (rg>0.6), processing speed (rg>0.7) and memory (rg>0.3). Polygenic profile analysis indicated considerable shared genetic aetiology between trail making, general cognitive function, processing speed and memory (standardized ß between 0.03 and 0.08). These results suggest that trail making is both phenotypically and genetically strongly associated with general cognitive function and processing speed.

Genetic contributions to self-reported tiredness.

This corrects the article DOI: 10.1038/mp.2017.5.

Effect of asthma and six-months high-intensity interval training on heart rate variability during exercise in adolescents.

Little is known regarding the influence of asthma and exercise, and their interaction, on heart rate variability (HRV) in adolescents. Thirty-one adolescents with asthma (13.7±0.9 years; 21.9±3.9 kg·m-2; 19 boys, 12 girls) and thirty-three healthy adolescents (13.8±0.9 years; 20.3±3.2 kg·m-2; 16 boys, 17 girls) completed an incremental ramp test and three heavy-intensity constant-work-rate cycle tests. Thirteen adolescents (7 boys, 6 girls; 6 asthma, 7 control) completed six-months high-intensity interval training (HIIT) and were compared to age- and sex-matched controls. Standard time-domain, frequency-domain and non-linear indices of HRV were derived at baseline, three- and six-months. Asthma did not influence HRV at baseline or following HIIT. Total power, low frequency and normalised low frequency power, and sympathovagal balance increased at three-months in HIIT, subsequently declining towards baseline at six-months. Normalised high frequency power was reduced at three-months in both groups, which was sustained at six-months. No effects of HIIT were observed in the time-domain nor in the non-linear indices. HRV was not influenced by asthma, potentially because such derangements are a function of disease progression, severity or duration. HIIT may be associated with a short-term shift towards greater sympathetic predominance during exercise, perhaps caused by physiological overload and fatigue.

Increased fire severity alters initial vegetation regeneration across Calluna-dominated ecosystems.

Calluna vulgaris-dominated habitats are valued for ecosystem services such as carbon storage and for their conservation importance. Climate and environmental change are altering their fire regimes. In particular, more frequent summer droughts will result in higher severity wildfires. This could alter the plant community composition of Calluna habitats and thereby influence ecosystem function. To study the effect of fire severity on community composition we used rain-out shelters to simulate drought prior to experimental burns at two Calluna-dominated sites, a raised bog and a heathland. We analysed species abundance in plots surveyed ca. 16 months after fire in relation to burn severity (indicated by fire-induced soil heating). We found that fire severity was an important control on community composition at both sites. Higher fire severity increased the abundance of ericoids, graminoids and acrocarpous mosses, and decreased the abundance of pleurocarpous mosses compared to lower severity fires. At the raised bog, the keystone species Sphagnum capillifolium and Eriophorum vaginatum showed no difference in regeneration with fire severity. Species and plant functional type beta-diversity increased following fire, and was similar in higher compared to lower severity burns. Our results further our understanding of the response of Calluna-dominated habitats to projected changes in fire regimes, and can assist land managers using prescribed fires in selecting burning conditions to achieve management objectives.

Burning increases post-fire carbon emissions in a heathland and a raised bog, but experimental manipulation of fire severity has no effect.

Large amounts of carbon are stored in northern peatlands. There is concern that greater wildfire severity following projected increases in summer drought will lead to higher post-fire carbon losses. We measured soil carbon dynamics in a Calluna heathland and a raised peat bog after experimentally manipulating fire severity. A gradient of fire severity was achieved by simulating drought in 2 × 2 m plots. Ecosystem respiration (ER), net ecosystem exchange (NEE), methane (CH4) flux and concentration of dissolved organic carbon ([DOC], measured at the raised bog only) were measured for up to two years after burning. The response of these carbon fluxes to increased fire severity in drought plots was similar to plots burnt under ambient conditions associated with traditional managed burning. Averaged across all burnt plots, burning altered mean NEE from a net carbon sink at the heathland (-0.33 µmol CO2 m-2 s-1 in unburnt plots) to a carbon source (0.50 µmol m-2 s-1 in burnt plots) and at the raised bog (-0.38 and 0.16 µmol m-2 s-1, respectively). Burning also increased CH4 flux at the raised bog (from 1.16 to 25.3 nmol m-2 s-1 in the summer, when it accounted for 79% of the CO2-equivalent emission). Burning had no significant effect on soil water [DOC].

Pharmacokinetics of rifampicin in adult TB patients and healthy volunteers: a systematic review and meta-analysis.

Objectives: The objectives of this study were to explore inter-study heterogeneity in the pharmacokinetics (PK) of orally administered rifampicin, to derive summary estimates of rifampicin PK parameters at standard dosages and to compare these with summary estimates for higher dosages. Methods: A systematic search was performed for studies of rifampicin PK published in the English language up to May 2017. Data describing the Cmax and AUC were extracted. Meta-analysis provided summary estimates for PK parameter estimates at standard rifampicin dosages. Heterogeneity was assessed by estimation of the I2 statistic and visual inspection of forest plots. Summary AUC estimates at standard and higher dosages were compared graphically and contextualized using preclinical pharmacodynamic (PD) data. Results: Substantial heterogeneity in PK parameters was evident and upheld in meta-regression. Treatment duration had a significant impact on the summary estimates for rifampicin PK parameters, with Cmax 8.98 mg/L (SEM 2.19) after a single dose and 5.79 mg/L (SEM 2.14) at steady-state dosing, and AUC 72.56 mg·h/L (SEM 2.60) and 38.73 mg·h/L (SEM 4.33) after single and steady-state dosing, respectively. Rifampicin dosages of at least 25 mg/kg are required to achieve plasma PK/PD targets defined in preclinical studies. Conclusions: Vast inter-study heterogeneity exists in rifampicin PK parameter estimates. This is not explained by the available modifying variables. The recommended dosage of rifampicin should be increased to improve efficacy. This study provides an important point of reference for understanding rifampicin PK at standard dosages as efforts to explore higher dosing strategies continue in this field.

Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117).

Alcohol consumption has been linked to over 200 diseases and is responsible for over 5% of the global disease burden. Well-known genetic variants in alcohol metabolizing genes, for example, ALDH2 and ADH1B, are strongly associated with alcohol consumption but have limited impact in European populations where they are found at low frequency. We performed a genome-wide association study (GWAS) of self-reported alcohol consumption in 112 117 individuals in the UK Biobank (UKB) sample of white British individuals. We report significant genome-wide associations at 14 loci. These include single-nucleotide polymorphisms (SNPs) in alcohol metabolizing genes (ADH1B/ADH1C/ADH5) and two loci in KLB, a gene recently associated with alcohol consumption. We also identify SNPs at novel loci including GCKR, CADM2 and FAM69C. Gene-based analyses found significant associations with genes implicated in the neurobiology of substance use (DRD2, PDE4B). GCTA analyses found a significant SNP-based heritability of self-reported alcohol consumption of 13% (se=0.01). Sex-specific analyses found largely overlapping GWAS loci and the genetic correlation (rG) between male and female alcohol consumption was 0.90 (s.e.=0.09, P-value=7.16 × 10-23). Using LD score regression, genetic overlap was found between alcohol consumption and years of schooling (rG=0.18, s.e.=0.03), high-density lipoprotein cholesterol (rG=0.28, s.e.=0.05), smoking (rG=0.40, s.e.=0.06) and various anthropometric traits (for example, overweight, rG=-0.19, s.e.=0.05). This study replicates the association between alcohol consumption and alcohol metabolizing genes and KLB, and identifies novel gene associations that should be the focus of future studies investigating the neurobiology of alcohol consumption.

GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium.

This corrects the article DOI: 10.1038/mp.2016.244.

GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium.

The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (~8M single-nucleotide polymorphisms (SNP) with minor allele frequency ⩾1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (P<5 × 10-8). Gene-based analysis identified an additional three Bonferroni-corrected significant loci at chromosomes 17q21.31, 17p13.1 and 1p13.3. Altogether, common variation across the genome resulted in a conservatively estimated SNP heritability of 21.5% (s.e.=0.01%) for general cognitive function. Integration with prior GWAS of cognitive performance and educational attainment yielded several additional significant loci. Finally, we found robust polygenic correlations between cognitive performance and educational attainment, several psychiatric disorders, birth length/weight and smoking behavior, as well as a novel genetic association to the personality trait of openness. These data provide new insight into the genetics of neurocognitive function with relevance to understanding the pathophysiology of neuropsychiatric illness.

Perceptions of asthma and exercise in adolescents with and without asthma.

OBJECTIVE: To elicit the views of adolescents, with and without asthma, about exercise and asthma, and the perceived benefits of and barriers to participation. The adolescent views elicited would subsequently inform the design of a high-intensity exercise intervention to improve asthma control. METHODS: Fifty-four adolescents (age 13.1 ± 0.9 years; 26 with asthma) participated in twelve semi-structured group interviews. Questions were structured around knowledge, attitudes and beliefs towards asthma and its impact on exercise participation and lifestyle. The interviews were transcribed verbatim, thematically analysed and presented via diagrams of emergent themes. Ethical approval was granted by the institutional research ethics committee. RESULTS: Fear of an asthma attack emerged as the main barrier to exercise, with many adolescents with asthma withdrawing from exercise as a coping strategy; many healthy adolescents perceived this withdrawal as laziness or an excuse. Despite this, the majority (81%) of adolescents with asthma reported exercise to be their most enjoyable activity. Adolescents suggested incorporating mixed activities, such as team games (e.g., rounders, football, netball), for future interventions to ensure adherence. CONCLUSIONS: Whilst exercise is important in the management of asthma, the tendency of those with asthma to withdraw from exercise to avoid adverse events could be addressed through a games-based high-intensity exercise intervention. Furthermore, educating all adolescents on asthma could simultaneously reduce stigmatisation and enhance exercise engagement.

The relationship between pre-operative hypertension and intra-operative haemodynamic changes known to be associated with postoperative morbidity.

Hypertension is not consistently associated with postoperative cardiovascular morbidity and is therefore not considered a major peri-operative risk factor. However, hypertension may predispose to peri-operative haemodynamic changes known to be associated with peri-operative morbidity and mortality, such as intra-operative hypotension and tachycardia. The objective of this study was to determine whether pre-operative hypertension was independently associated with haemodynamic changes known to be associated with adverse peri-operative outcomes. We performed a five-day multicentre, prospective, observational cohort study which included all adult inpatients undergoing elective, non-cardiac, non-obstetric surgery. We recruited 343 patients of whom 164 (47.8%) were hypertensive. An intra-operative mean arterial pressure of < 55 mmHg occurred in 59 (18.2%) patients, of which 25 (42.4%) were hypertensive. Intra-operative tachycardia (heart rate> 100 beats.min-1 ) occurred in 126 (38.9%) patients, of whom 61 (48.4%) were hypertensive. Multivariable logistic regression did not show an independent association between the stage of hypertension and either clinically significant hypotension or tachycardia, when controlled for ASA physical status, functional status, major surgery, duration of surgery or blood transfusion. There was no association between pre-operative hypertension and peri-operative haemodynamic changes known to be associated with major morbidity and mortality. These data, therefore, support the recommendation of the Joint Guidelines of the Association of Anaesthetists of Great Britain and Ireland (AAGBI) and the British Hypertension Society to proceed with elective surgery if a patient's blood pressure is < 180/110 mmHg.

Seeking, accepting and declining help for emotional distress in cancer: A systematic review and thematic synthesis of qualitative evidence.

Many individuals affected by cancer who experience emotional distress report not wanting help. This review aims to understand why individuals affected by cancer seek, accept or decline help for emotional distress and what influences these actions. A systematic review and thematic synthesis of the qualitative literature was conducted. Using pre-defined search terms, four electronic databases were searched from January 2000 to May 2016. Pre-determined inclusion and exclusion criteria were then applied. Identified papers were quality appraised. In total, 32 papers were included in the synthesis. Four themes emerged from data synthesis: attaining normality-the normality paradox; being emotionally literate; perceptions of help; needs-support gap. Attaining normality is ideographic, context dependent and temporally situated; some individuals maintain normality by not seeking/declining help whereas others seek/accept help to achieve a new normality. Thus, attaining normality paradoxically functions to explain both why individuals sought/accepted help or did not seek/declined help. Data indicate that a context dependent, systems thinking approach is merited to enhance psychosocial care. In particular, clinicians must actively explore the personal context of an individual's distress to ensure that help desired and help offered are mutually understood. Further research must address the limitations of the current evidence base to advance theoretical understanding.