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Brighton and Sussex Medical School

UniversityBrighton, United Kingdom

Research output, citation impact, and the most-cited recent papers from Brighton and Sussex Medical School (United Kingdom). Aggregated across the NobleBlocks index of 300M+ scholarly works.

Total works
10.2K
Citations
549.4K
h-index
281
i10-index
7.2K
Also known as
Brighton and Sussex Medical School

Top-cited papers from Brighton and Sussex Medical School

Treatment of Hypertension in Patients 80 Years of Age or Older
Nigel Beckett, Ruth Peters, Astrid Fletcher, Jan A. Staessen +4 more
2008· New England Journal of Medicine3.1Kdoi:10.1056/nejmoa0801369

BACKGROUND: Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear. It has been suggested that antihypertensive therapy may reduce the risk of stroke, despite possibly increasing the risk of death. METHODS: We randomly assigned 3845 patients from Europe, China, Australasia, and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide (sustained release, 1.5 mg) or matching placebo. The angiotensin-converting-enzyme inhibitor perindopril (2 or 4 mg), or matching placebo, was added if necessary to achieve the target blood pressure of 150/80 mm Hg. The primary end point was fatal or nonfatal stroke. RESULTS: The active-treatment group (1933 patients) and the placebo group (1912 patients) were well matched (mean age, 83.6 years; mean blood pressure while sitting, 173.0/90.8 mm Hg); 11.8% had a history of cardiovascular disease. Median follow-up was 1.8 years. At 2 years, the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group. In an intention-to-treat analysis, active treatment was associated with a 30% reduction in the rate of fatal or nonfatal stroke (95% confidence interval [CI], -1 to 51; P=0.06), a 39% reduction in the rate of death from stroke (95% CI, 1 to 62; P=0.05), a 21% reduction in the rate of death from any cause (95% CI, 4 to 35; P=0.02), a 23% reduction in the rate of death from cardiovascular causes (95% CI, -1 to 40; P=0.06), and a 64% reduction in the rate of heart failure (95% CI, 42 to 78; P<0.001). Fewer serious adverse events were reported in the active-treatment group (358, vs. 448 in the placebo group; P=0.001). CONCLUSIONS: The results provide evidence that antihypertensive treatment with indapamide (sustained release), with or without perindopril, in persons 80 years of age or older is beneficial. (ClinicalTrials.gov number, NCT00122811 [ClinicalTrials.gov].).

The Global Burden of Cancer 2013
Christina Fitzmaurice, Daniel Dicker, Amanda Pain, Hannah Hamavid +4 more
2015· JAMA Oncology2.8Kdoi:10.1001/jamaoncol.2015.0735

IMPORTANCE: Cancer is among the leading causes of death worldwide. Current estimates of cancer burden in individual countries and regions are necessary to inform local cancer control strategies. OBJECTIVE: To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 28 cancers in 188 countries by sex from 1990 to 2013. EVIDENCE REVIEW: The general methodology of the Global Burden of Disease (GBD) 2013 study was used. Cancer registries were the source for cancer incidence data as well as mortality incidence (MI) ratios. Sources for cause of death data include vital registration system data, verbal autopsy studies, and other sources. The MI ratios were used to transform incidence data to mortality estimates and cause of death estimates to incidence estimates. Cancer prevalence was estimated using MI ratios as surrogates for survival data; YLDs were calculated by multiplying prevalence estimates with disability weights, which were derived from population-based surveys; YLLs were computed by multiplying the number of estimated cancer deaths at each age with a reference life expectancy; and DALYs were calculated as the sum of YLDs and YLLs. FINDINGS: In 2013 there were 14.9 million incident cancer cases, 8.2 million deaths, and 196.3 million DALYs. Prostate cancer was the leading cause for cancer incidence (1.4 million) for men and breast cancer for women (1.8 million). Tracheal, bronchus, and lung (TBL) cancer was the leading cause for cancer death in men and women, with 1.6 million deaths. For men, TBL cancer was the leading cause of DALYs (24.9 million). For women, breast cancer was the leading cause of DALYs (13.1 million). Age-standardized incidence rates (ASIRs) per 100 000 and age-standardized death rates (ASDRs) per 100 000 for both sexes in 2013 were higher in developing vs developed countries for stomach cancer (ASIR, 17 vs 14; ASDR, 15 vs 11), liver cancer (ASIR, 15 vs 7; ASDR, 16 vs 7), esophageal cancer (ASIR, 9 vs 4; ASDR, 9 vs 4), cervical cancer (ASIR, 8 vs 5; ASDR, 4 vs 2), lip and oral cavity cancer (ASIR, 7 vs 6; ASDR, 2 vs 2), and nasopharyngeal cancer (ASIR, 1.5 vs 0.4; ASDR, 1.2 vs 0.3). Between 1990 and 2013, ASIRs for all cancers combined (except nonmelanoma skin cancer and Kaposi sarcoma) increased by more than 10% in 113 countries and decreased by more than 10% in 12 of 188 countries. CONCLUSIONS AND RELEVANCE: Cancer poses a major threat to public health worldwide, and incidence rates have increased in most countries since 1990. The trend is a particular threat to developing nations with health systems that are ill-equipped to deal with complex and expensive cancer treatments. The annual update on the Global Burden of Cancer will provide all stakeholders with timely estimates to guide policy efforts in cancer prevention, screening, treatment, and palliation.

British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults
Christopher A Lamb, Nicholas A. Kennedy, Tim Raine, Philip Hendy +4 more
2019· Gut2.4Kdoi:10.1136/gutjnl-2019-318484

Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.

Using Bayes to get the most out of non-significant results
Zoltán Dienes
2014· Frontiers in Psychology2.1Kdoi:10.3389/fpsyg.2014.00781

No scientific conclusion follows automatically from a statistically non-significant result, yet people routinely use non-significant results to guide conclusions about the status of theories (or the effectiveness of practices). To know whether a non-significant result counts against a theory, or if it just indicates data insensitivity, researchers must use one of: power, intervals (such as confidence or credibility intervals), or else an indicator of the relative evidence for one theory over another, such as a Bayes factor. I argue Bayes factors allow theory to be linked to data in a way that overcomes the weaknesses of the other approaches. Specifically, Bayes factors use the data themselves to determine their sensitivity in distinguishing theories (unlike power), and they make use of those aspects of a theory's predictions that are often easiest to specify (unlike power and intervals, which require specifying the minimal interesting value in order to address theory). Bayes factors provide a coherent approach to determining whether non-significant results support a null hypothesis over a theory, or whether the data are just insensitive. They allow accepting and rejecting the null hypothesis to be put on an equal footing. Concrete examples are provided to indicate the range of application of a simple online Bayes calculator, which reveal both the strengths and weaknesses of Bayes factors.

3rd ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3)
Fátima Cardoso, A. Costa, Elżbieta Senkus, Matti Aapro +4 more
2016· Annals of Oncology2.1Kdoi:10.1093/annonc/mdw544

Advanced Breast Cancer (ABC) comprises both locally advanced (LABC) and metastatic breast cancer (MBC) [1]. Although treatable, MBC remains an incurable disease with a median overall survival of ∼2–3 years and a 5-year survival of only ∼25% [2–4]. Some more recent series seem to indicate an improvement in median overall survival [5, 6].

Randomized Multicenter Trial of Sentinel Node Biopsy Versus Standard Axillary Treatment in Operable Breast Cancer: The ALMANAC Trial
Robert E. Mansel, Lesley Fallowfield, Mark Kissin, Amit Goyal +4 more
2006· JNCI Journal of the National Cancer Institute1.7Kdoi:10.1093/jnci/djj158

BACKGROUND: Sentinel lymph node biopsy in women with operable breast cancer is routinely used in some countries for staging the axilla despite limited data from randomized trials on morbidity and mortality outcomes. We conducted a multicenter randomized trial to compare quality-of-life outcomes between patients with clinically node-negative invasive breast cancer who received sentinel lymph node biopsy and patients who received standard axillary treatment. METHODS: The primary outcome measures were arm and shoulder morbidity and quality of life. From November 1999 to October 2003, 1031 patients were randomly assigned to undergo sentinel lymph node biopsy (n = 515) or standard axillary surgery (n = 516). Patients with sentinel lymph node metastases proceeded to delayed axillary clearance or received axillary radiotherapy (depending on the protocol at the treating institution). Intention-to-treat analyses of data at 1, 3, 6, and 12 months after surgery are presented. All statistical tests were two-sided. RESULTS: The relative risks of any lymphedema and sensory loss for the sentinel lymph node biopsy group compared with the standard axillary treatment group at 12 months were 0.37 (95% confidence interval [CI] = 0.23 to 0.60; absolute rates: 5% versus 13%) and 0.37 (95% CI = 0.27 to 0.50; absolute rates: 11% versus 31%), respectively. Drain usage, length of hospital stay, and time to resumption of normal day-to-day activities after surgery were statistically significantly lower in the sentinel lymph node biopsy group (all P < .001), and axillary operative time was reduced (P = .055). Overall patient-recorded quality of life and arm functioning scores were statistically significantly better in the sentinel lymph node biopsy group throughout (all P < or = .003). These benefits were seen with no increase in anxiety levels in the sentinel lymph node biopsy group (P > .05). CONCLUSION: Sentinel lymph node biopsy is associated with reduced arm morbidity and better quality of life than standard axillary treatment and should be the treatment of choice for patients who have early-stage breast cancer with clinically negative nodes.

Knowing your own heart: Distinguishing interoceptive accuracy from interoceptive awareness
Sarah N. Garfinkel, Anil K. Seth, Adam B. Barrett, Keisuke Suzuki +1 more
2014· Biological Psychology1.6Kdoi:10.1016/j.biopsycho.2014.11.004

Interoception refers to the sensing of internal bodily changes. Interoception interacts with cognition and emotion, making measurement of individual differences in interoceptive ability broadly relevant to neuropsychology. However, inconsistency in how interoception is defined and quantified led to a three-dimensional model. Here, we provide empirical support for dissociation between dimensions of: (1) interoceptive accuracy (performance on objective behavioural tests of heartbeat detection), (2) interoceptive sensibility (self-evaluated assessment of subjective interoception, gauged using interviews/questionnaires) and (3) interoceptive awareness (metacognitive awareness of interoceptive accuracy, e.g. confidence-accuracy correspondence). In a normative sample (N=80), all three dimensions were distinct and dissociable. Interoceptive accuracy was only partly predicted by interoceptive awareness and interoceptive sensibility. Significant correspondence between dimensions emerged only within the sub-group of individuals with greatest interoceptive accuracy. These findings set the context for defining how the relative balance of accuracy, sensibility and awareness dimensions explain cognitive, emotional and clinical associations of interoceptive ability.

5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5)
Fátima Cardoso, Shani Paluch–Shimon, Elżbieta Senkus, Giuseppe Curigliano +4 more
2020· Annals of Oncology1.4Kdoi:10.1016/j.annonc.2020.09.010

For the purpose of advanced breast cancer (ABC) guidelines, ABC comprises both inoperable locally advanced breast cancer (LABC) and metastatic breast cancer (MBC).1,2 Advanced/metastatic breast cancer remains a virtually incurable disease, with a median overall survival (OS) of about 3 years and a 5-year survival rate of around 25%,3,4 even in countries without major accessibility problems. Survival is strongly related to breast cancer subtype, with the major advances seen in human epidermal growth factor receptor 2 (HER2)-positive ABC.

Neutrophil kinetics in health and disease
Charlotte Summers, Sara M. Rankin, Alison M. Condliffe, Nanak Singh +2 more
2010· Trends in Immunology1.2Kdoi:10.1016/j.it.2010.05.006

Neutrophils play a key role in the elimination of pathogens. They are remarkably short-lived with a circulating half life of 6-8h and hence are produced at a rate of 5x10(10)-10x10(10) cells/day. Tight regulation of these cells is vital because they have significant histotoxic capacity and are widely implicated in tissue injury. This review outlines our current understanding of how neutrophils are released from the bone marrow; in particular, the role of the CXC chemokine receptor 4/stromal-derived factor 1 axis, the relative size and role of the freely circulating and marginated (i.e. slowly transiting) pools within the vascular compartment, and the events that result in the uptake and removal of circulating neutrophils. We also review current understanding of how systemic stress and inflammation affect this finely balanced system.

4th ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4)
Fátima Cardoso, Elżbieta Senkus, A. Costa, Efthymios Papadopoulos +4 more
2018· Annals of Oncology1.2Kdoi:10.1093/annonc/mdy192

Advanced Breast Cancer (ABC) comprises both locally advanced breast cancer (LABC) and metastatic breast cancer (MBC) [1]. Although treatable, MBC remains virtually an incurable disease with a median overall survival (OS) of ∼3years and a 5-year survival of only ∼25% [2, 3]. The MBC Decade Report [2] shows that progress has been slow in terms of improved outcomes, quality of life (QoL), awareness and information regarding ABC. More recently, some studies seem to indicate an improvement in OS, mostly due to advances in human epidermal growth factor receptor 2 (HER2)-positive ABC [4–6].

Income distribution and life expectancy.
Richard G. Wilkinson
1992· BMJ1.2Kdoi:10.1136/bmj.304.6820.165

The relationship between income distribution and mortality is explored using data from published sources. Specifically the author attempts to investigate the cross sectional relation between income distribution and mortality and its possible interactions with gross national product per head and to assess whether changes in income distribution over time are related to changes in mortality in developed countries. He concludes that there is clear evidence of a strong relation between a societys income distribution and the average life expectancy of its population. (EXCERPT)

The global threat of antimicrobial resistance: science for intervention
Ignasi Roca, Murat Akova, Fernando Baquero, Jean Carlet +4 more
2015· New Microbes and New Infections1.1Kdoi:10.1016/j.nmni.2015.02.007

In the last decade we have witnessed a dramatic increase in the proportion and absolute number of bacterial pathogens resistant to multiple antibacterial agents. Multidrug-resistant bacteria are currently considered as an emergent global disease and a major public health problem. The B-Debate meeting brought together renowned experts representing the main stakeholders (i.e. policy makers, public health authorities, regulatory agencies, pharmaceutical companies and the scientific community at large) to review the global threat of antibiotic resistance and come up with a coordinated set of strategies to fight antimicrobial resistance in a multifaceted approach. We summarize the views of the B-Debate participants regarding the current situation of antimicrobial resistance in animals and the food chain, within the community and the healthcare setting as well as the role of the environment and the development of novel diagnostic and therapeutic strategies, providing expert recommendations to tackle the global threat of antimicrobial resistance.

Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial
Ian Jacobs, Usha Menon, Andy Ryan, Aleksandra Gentry‐Maharaj +4 more
2015· The Lancet1.1Kdoi:10.1016/s0140-6736(15)01224-6

BACKGROUND: Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality. METHODS: In this randomised controlled trial, we recruited postmenopausal women aged 50-74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer-generated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032. FINDINGS: Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202,638 women: 50,640 (25·0%) to MMS, 50,639 (25·0%) to USS, and 101,359 (50·0%) to no screening. 202,546 (>99·9%) women were eligible for analysis: 50,624 (>99·9%) women in the MMS group, 50,623 (>99·9%) in the USS group, and 101,299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345,570 MMS and 327,775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0-12·0), we diagnosed ovarian cancer in 1282 (0·6%) women: 338 (0·7%) in the MMS group, 314 (0·6%) in the USS group, and 630 (0·6%) in the no screening group. Of these women, 148 (0·29%) women in the MMS group, 154 (0·30%) in the USS group, and 347 (0·34%) in the no screening group had died of ovarian cancer. The primary analysis using a Cox proportional hazards model gave a mortality reduction over years 0-14 of 15% (95% CI -3 to 30; p=0·10) with MMS and 11% (-7 to 27; p=0·21) with USS. The Royston-Parmar flexible parametric model showed that in the MMS group, this mortality effect was made up of 8% (-20 to 31) in years 0-7 and 23% (1-46) in years 7-14, and in the USS group, of 2% (-27 to 26) in years 0-7 and 21% (-2 to 42) in years 7-14. A prespecified analysis of death from ovarian cancer of MMS versus no screening with exclusion of prevalent cases showed significantly different death rates (p=0·021), with an overall average mortality reduction of 20% (-2 to 40) and a reduction of 8% (-27 to 43) in years 0-7 and 28% (-3 to 49) in years 7-14 in favour of MMS. INTERPRETATION: Although the mortality reduction was not significant in the primary analysis, we noted a significant mortality reduction with MMS when prevalent cases were excluded. We noted encouraging evidence of a mortality reduction in years 7-14, but further follow-up is needed before firm conclusions can be reached on the efficacy and cost-effectiveness of ovarian cancer screening. FUNDING: Medical Research Council, Cancer Research UK, Department of Health, The Eve Appeal.

Imaging biomarker roadmap for cancer studies
James P.B. O’Connor, Eric O. Aboagye, Judith E. Adams, Hugo J.W.L. Aerts +4 more
2016· Nature Reviews Clinical Oncology1.1Kdoi:10.1038/nrclinonc.2016.162

Imaging biomarkers (IBs) are used extensively in drug development and cancer research, but important differences exist between IBs and biospecimen-derived biomarkers. A tailored 'roadmap' is required for the development of new IBs to be used either in clinical research or for decision-making in healthcare. In this Consensus statement, a group of experts assembled by CRUK and the EORTC present 14 key recommendations for accelerating the clinical translation of IBs. Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.

Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study
Alison Rodger, Valentina Cambiano, Tina Bruun, Pietro Vernazza +4 more
2019· The Lancet1.0Kdoi:10.1016/s0140-6736(19)30418-0

BACKGROUND: The level of evidence for HIV transmission risk through condomless sex in serodifferent gay couples with the HIV-positive partner taking virally suppressive antiretroviral therapy (ART) is limited compared with the evidence available for transmission risk in heterosexual couples. The aim of the second phase of the PARTNER study (PARTNER2) was to provide precise estimates of transmission risk in gay serodifferent partnerships. METHODS: The PARTNER study was a prospective observational study done at 75 sites in 14 European countries. The first phase of the study (PARTNER1; Sept 15, 2010, to May 31, 2014) recruited and followed up both heterosexual and gay serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex, whereas the PARTNER2 extension (to April 30, 2018) recruited and followed up gay couples only. At study visits, data collection included sexual behaviour questionnaires, HIV testing (HIV-negative partner), and HIV-1 viral load testing (HIV-positive partner). If a seroconversion occurred in the HIV-negative partner, anonymised phylogenetic analysis was done to compare HIV-1 pol and env sequences in both partners to identify linked transmissions. Couple-years of follow-up were eligible for inclusion if condomless sex was reported, use of pre-exposure prophylaxis or post-exposure prophylaxis was not reported by the HIV-negative partner, and the HIV-positive partner was virally suppressed (plasma HIV-1 RNA <200 copies per mL) at the most recent visit (within the past year). Incidence rate of HIV transmission was calculated as the number of phylogenetically linked HIV infections that occurred during eligible couple-years of follow-up divided by eligible couple-years of follow-up. Two-sided 95% CIs for the incidence rate of transmission were calculated using exact Poisson methods. FINDINGS: Between Sept 15, 2010, and July 31, 2017, 972 gay couples were enrolled, of which 782 provided 1593 eligible couple-years of follow-up with a median follow-up of 2·0 years (IQR 1·1-3·5). At baseline, median age for HIV-positive partners was 40 years (IQR 33-46) and couples reported condomless sex for a median of 1·0 years (IQR 0·4-2·9). During eligible couple-years of follow-up, couples reported condomless anal sex a total of 76 088 times. 288 (37%) of 777 HIV-negative men reported condomless sex with other partners. 15 new HIV infections occurred during eligible couple-years of follow-up, but none were phylogenetically linked within-couple transmissions, resulting in an HIV transmission rate of zero (upper 95% CI 0·23 per 100 couple-years of follow-up). INTERPRETATION: Our results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV. FUNDING: National Institute for Health Research.

An Interoceptive Predictive Coding Model of Conscious Presence
Anil K. Seth, Keisuke Suzuki, Hugo Critchley
2012· Frontiers in Psychology978doi:10.3389/fpsyg.2011.00395

We describe a theoretical model of the neurocognitive mechanisms underlying conscious presence and its disturbances. The model is based on interoceptive prediction error and is informed by predictive models of agency, general models of hierarchical predictive coding and dopaminergic signaling in cortex, the role of the anterior insular cortex (AIC) in interoception and emotion, and cognitive neuroscience evidence from studies of virtual reality and of psychiatric disorders of presence, specifically depersonalization/derealization disorder. The model associates presence with successful suppression by top-down predictions of informative interoceptive signals evoked by autonomic control signals and, indirectly, by visceral responses to afferent sensory signals. The model connects presence to agency by allowing that predicted interoceptive signals will depend on whether afferent sensory signals are determined, by a parallel predictive-coding mechanism, to be self-generated or externally caused. Anatomically, we identify the AIC as the likely locus of key neural comparator mechanisms. Our model integrates a broad range of previously disparate evidence, makes predictions for conjoint manipulations of agency and presence, offers a new view of emotion as interoceptive inference, and represents a step toward a mechanistic account of a fundamental phenomenological property of consciousness.

Interoception and emotion
Hugo Critchley, Sarah N. Garfinkel
2017· Current Opinion in Psychology912doi:10.1016/j.copsyc.2017.04.020

Influential theories suggest emotional feeling states arise from physiological changes from within the body. Interoception describes the afferent signalling, central processing, and neural and mental representation of internal bodily signals. Recent progress is made in conceptualizing interoception and its neural underpinnings. These developments are supported by empirical data concerning interoceptive mechanisms and their contribution to emotion. Fresh insights include description of short-term interoceptive effects on neural and mental processes (including fear-specific cardiac effects), the recognition of dissociable psychological dimensions of interoception, and models of interoceptive predictive coding that explain emotions and selfhood (reinforced by structural anatomical models and brain and experimental findings). This growing grasp of interoception is enriching our understanding of emotion and its disorders.

Clinical Relevance of Biomarkers of Oxidative Stress
Jeroen Frijhoff, Paul G. Winyard, Neven Žarković, Sean S. Davies +4 more
2015· Antioxidants and Redox Signaling909doi:10.1089/ars.2015.6317

SIGNIFICANCE: Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino acids. RECENT ADVANCES: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. CRITICAL ISSUES: The literature is very heterogeneous. It is often difficult to draw general conclusions on the significance of oxidative stress biomarkers, as only in a limited proportion of diseases have a range of different biomarkers been used, and different biomarkers have been used to study different diseases. In addition, biomarkers are often measured using nonspecific methods, while specific methodologies are often too sophisticated or laborious for routine clinical use. FUTURE DIRECTIONS: Several markers of oxidative stress still represent a viable biomarker opportunity for clinical use. However, positive findings with currently used biomarkers still need to be validated in larger sample sizes and compared with current clinical standards to establish them as clinical diagnostics. It is important to realize that oxidative stress is a nuanced phenomenon that is difficult to characterize, and one biomarker is not necessarily better than others. The vast diversity in oxidative stress between diseases and conditions has to be taken into account when selecting the most appropriate biomarker.

Socioeconomic determinants of health: Health inequalities: relative or absolute material standards?
Richard G. Wilkinson
1997· BMJ889doi:10.1136/bmj.314.7080.591

That mortality in developed countries is affected more by relative than absolute living standards is shown by three pieces of evidence. Firstly, mortality is related more closely to relative income within countries than to differences in absolute income between them. Secondly, national mortality rates tend to be lowest in countries that have smaller income differences and thus have lower levels of relative deprivation. Thirdly, most of the long term rise in life expectancy seems unrelated to long term economic growth rates. Although both material and social influences contribute to inequalities in health, the importance of relative standards implies that psychosocial pathways may be particularly influential. During the 1980s income differences widened more rapidly in Britain than in other countries; almost a quarter of the population now lives in relative poverty. The effects of higher levels of relative deprivation and lower social cohesion may already be visible in mortality trends among young adults. A “feel bad” factor in the health divide? TONY WALLIS The existence of wide-and widening-socioeconomic differences in health shows how extraordinarily sensitive health remains to socioeconomic circumstances. Twofold, threefold, or even fourfold differences in mortality have been reported within Britain, depending largely on the social classification used.1 2 3 This series will illustrate some of the most important mechanisms involved in the generation of these differences. Fundamental to understanding the causes of these differences in health is the distinction between the effects of relative and absolute living standards. Socioeconomic gradients in health are simultaneously an association with social position and with different material circumstances, both of which have implications for health-but which is more important in terms of causality? Is the health disadvantage of the least well off part of the population mainly a reflection of the direct physiological effects of lower absolute material standards (of bad …

Assessment of tumor heterogeneity: an emerging imaging tool for clinical practice?
F. Davnall, Connie Yip, Gunnar Ljungqvist, Mariyah Selmi +4 more
2012· Insights into Imaging884doi:10.1007/s13244-012-0196-6

BACKGROUND: Tumor spatial heterogeneity is an important prognostic factor, which may be reflected in medical images METHODS: Image texture analysis is an approach of quantifying heterogeneity that may not be appreciated by the naked eye. Different methods can be applied including statistical-, model-, and transform-based methods. RESULTS: Early evidence suggests that texture analysis has the potential to augment diagnosis and characterization as well as improve tumor staging and therapy response assessment in oncological practice. CONCLUSION: This review provides an overview of the application of texture analysis with different imaging modalities, CT, MRI, and PET, to date and describes the technical challenges that have limited its widespread clinical implementation so far. With further efforts to refine its application, image texture analysis has the potential to develop into a valuable clinical tool for oncologic imaging. TEACHING POINTS : • Tumor spatial heterogeneity is an important prognostic factor. • Image texture analysis is an approach of quantifying heterogeneity. • Different methods can be applied, including statistical-, model-, and transform-based methods. • Texture analysis could improve the diagnosis, tumor staging, and therapy response assessment.