Altered functional and structural brain network organization in autism.

Structural and functional underconnectivity have been reported for multiple brain regions, functional systems, and white matter tracts in individuals with autism spectrum disorders (ASD). Although recent developments in complex network analysis have established that the brain is a modular network exhibiting small-world properties, network level organization has not been carefully examined in ASD. Here we used resting-state functional MRI (n = 42 ASD, n = 37 typically developing; TD) to show that children and adolescents with ASD display reduced short and long-range connectivity within functional systems (i.e., reduced functional integration) and stronger connectivity between functional systems (i.e., reduced functional segregation), particularly in default and higher-order visual regions. Using graph theoretical methods, we show that pairwise group differences in functional connectivity are reflected in network level reductions in modularity and clustering (local efficiency), but shorter characteristic path lengths (higher global efficiency). Structural networks, generated from diffusion tensor MRI derived fiber tracts (n = 51 ASD, n = 43 TD), displayed lower levels of white matter integrity yet higher numbers of fibers. TD and ASD individuals exhibited similar levels of correlation between raw measures of structural and functional connectivity (n = 35 ASD, n = 35 TD). However, a principal component analysis combining structural and functional network properties revealed that the balance of local and global efficiency between structural and functional networks was reduced in ASD, positively correlated with age, and inversely correlated with ASD symptom severity. Overall, our findings suggest that modeling the brain as a complex network will be highly informative in unraveling the biological basis of ASD and other neuropsychiatric disorders

Correlating peer and tutor assessment on a low-stakes engineering assignment

Peer assessment has been a subject of great debate in recent years. The way students perceive assessment and what motivates them when assessing may differ significantly from the tutor. This paper discusses a study designed to correlate students marking with the marks awarded by their tutors when peer assessing one another from in-class oral presentations. A new and alternative approach to correlate results is presented, which is based on the normalisation of the quantitative judgements based on determined criteria. The methodology was blind and holistic, as described in previous works: some guidelines were provided to the students on what is considered acceptable without getting into detail (holistic marking), and peer-assessment marks were made confidential (blind approach). It was observed that students have a tendency to overrate fellow students - especially where lower marks might be awarded. There is, however, direct agreement with the tutors marking in terms of qualitative judgements, which is highlighted by the presented correlation method used to adjust students marks. The presented methodology to correlate marks between the students and tutor showed to be a promising one. After processing the data with this simple and straightforward algorithm, peer and tutor assessment practically showed a perfect match

Case Report: Color as a Therapeutic Intervention

Peer reviewedFinal Accepted Versio

Negotiating professional and social voices in research principles and practice

This paper draws on work conducted for a qualitative interview based study which explores the gendered racialised and professional identifications of health and social care professionals. Participants for the project were drawn from the professional executive committees of recently formed Primary Care Trusts. The paper discusses how the feminist psychosocial methodological approach developed for the project is theoretically, practically and ethically useful in exploring the voices of those in positions of relative power in relation to both health and social care services and the social relations of gender and ethnicity. The approach draws on psychodynamic accounts of (defended) subjectivity and the feminist work of Carol Gilligan on a voice-centred relational methodology. Coupling the feminist with the psychosocial facilitates an emphasis on voice and dialogic communication between participant and researcher not always captured in psychosocial approaches which tend towards favouring the interviewer as ‘good listener’. This emphasis on dialogue is important in research contexts where prior and ongoing relationships with professional participants make it difficult and indeed undesirable for researchers to maintain silence

Assessing Australian women's knowledge and knowledge preferences about long-term health after hypertensive disorders of pregnancy: a survey study.

OBJECTIVES: To (1) assess women's current knowledge regarding long-term cardiovascular health after hypertensive disorders of pregnancy (2) elicit women's preferred educational content and format regarding health after hypertensive disorders of pregnancy. DESIGN AND SETTING: A custom-created online survey exploring Australian women's knowledge about long-term health after hypertensive disorders of pregnancy, distributed through consumer groups and social media. PARTICIPANTS: 266 women with (n=174) or without (n=92) a history of hypertensive disorders of pregnancy. PRIMARY AND SECONDARY OUTCOME MEASURES: (1) Proportion of women identifying long-term health risks after hypertensive disorder of pregnancy using a 10-point risk knowledge score with 0-4 'low', 4.1-7.0 'moderate' and 7.1-10 'high'. (2) Exploration of preferred content, format and distribution of educational material post hypertensive disorder of pregnancy. RESULTS: Knowledge scores about health after hypertensive disorder of pregnancy were moderate in groups with and without a history of the disorder. Knowledge was highest regarding risk of recurrent hypertensive disorders in a subsequent pregnancy, 'moderate' for chronic hypertension and heart attack, 'moderate' and 'low' regarding risk of heart disease and 'low' for diabetes and renal disease. Only 36% of all participants were aware that risks start within 10 years after the affected pregnancy. The majority of respondents with a history of hypertensive disorder of pregnancy (76%) preferred receiving information about long-term health 0-6 months post partum from a healthcare provider (80%), key organisations (60%), social media (47%) and brochures/flyers (43%). CONCLUSIONS: Women's knowledge regarding health risks after hypertensive disorder of pregnancy was 'moderate', although with important disease-specific gaps such as increased risk of diabetes. Most women wanted to be informed about their long-term health from a healthcare provider

Comparison of tumour-based (Petersen Index) and inflammation-based (Glasgow Prognostic Score) scoring systems in patients undergoing curative resection for colon cancer

After resection, it is important to identify colon cancer patients, who are at a high risk of recurrence and who may benefit from adjuvant treatment. The Petersen Index (PI), a prognostic model based on pathological criteria is validated in Dukes' B and C disease. Similarly, the modified Glasgow Prognostic Score (mGPS) based on biochemical criteria has also been validated. This study compares both the scores in patients undergoing curative resection of colon cancer. A total of 244 patients underwent elective resection between 1997 and 2005. The PI was constructed from pathological reports; the mGPS was measured pre-operatively. The median follow-up was 67 months (minimum 36 months) during which 109 patients died; 68 of them from cancer. On multivariate analysis of age, Dukes' stage, PI and mGPS, age (hazard ratio, HR, 1.74, P=0.001), Dukes' stage (HR, 3.63, P<0.001), PI (HR, 2.05, P=0.010) and mGPS (HR, 2.34, P<0.001) were associated independently with cancer-specific survival. Three-year cancer-specific survival rates for Dukes' B patients with the low-risk PI were 98, 92 and 82% for the mGPS of 0, 1 and 2, respectively (P<0.05). The high-risk PI population is small, in particular for Dukes' B disease (9%). The mGPS further stratifies those patients classified as low risk by the PI. Combining both the scoring systems could identify patients who have undergone curative surgery but are at high-risk of cancer-related death, therefore guiding management and trial stratification

The Fusion Loops of the Initial Prefusion Conformation of Herpes Simplex Virus 1 Fusion Protein Point Toward the Membrane

All enveloped viruses, including herpesviruses, must fuse their envelope with the host membrane to deliver their genomes into target cells, making this essential step subject to interference by antibodies and drugs. Viral fusion is mediated by a viral surface protein that transits from an initial prefusion conformation to a final postfusion conformation. Strikingly, the prefusion conformation of the herpesvirus fusion protein, gB, is poorly understood. Herpes simplex virus (HSV), a model system for herpesviruses, causes diseases ranging from mild skin lesions to serious encephalitis and neonatal infections. Using cryo-electron tomography and subtomogram averaging, we have characterized the structure of the prefusion conformation and fusion intermediates of HSV-1 gB. To this end, we have set up a system that generates microvesicles displaying full-length gB on their envelope. We confirmed proper folding of gB by nondenaturing electrophoresis-Western blotting with a panel of monoclonal antibodies (MAbs) covering all gB domains. To elucidate the arrangement of gB domains, we labeled them by using (i) mutagenesis to insert fluorescent proteins at specific positions, (ii) coexpression of gB with Fabs for a neutralizing MAb with known binding sites, and (iii) incubation of gB with an antibody directed against the fusion loops. Our results show that gB starts in a compact prefusion conformation with the fusion loops pointing toward the viral membrane and suggest, for the first time, a model for gB’s conformational rearrangements during fusion. These experiments further illustrate how neutralizing antibodies can interfere with the essential gB structural transitions that mediate viral entry and therefore infectivity

England SimSmoke: the impact of nicotine vaping on smoking prevalence and smoking‐attributable deaths in England

BACKGROUND AND AIMS: While the use of nicotine vaping products (NVPs) is widespread, their impact on smoking prevalence is controversial. This study considered the potential impact of NVPs on smoking prevalence in England. DESIGN: Indirect simulation model. The England SimSmoke model is validated through 2012, before NVP use became more widely used by smokers. Because information on NVP-related transitions is limited, an indirect method is used; the difference in observed smoking prevalence (reflecting NVPs) is compared with a 2012-2019 counterfactual No-NVP scenario (without NVPs) to estimate the impact of NVPs on smoking and smoking-attributable deaths. SETTING: England, 2000-2019. PARTICIPANTS: Nationally representative sample of population. MEASUREMENTS: England's population, mortality rates, and smoking prevalence estimates from three national surveys and tobacco control policies. FINDINGS: Between 2000 and 2012, SimSmoke projected a decline in age 18+ smoking prevalence of 23.5% in men and 27.0% in women. These projections, as well as those by specific age groups, were generally consistent with findings from the three national surveys. Comparing 2012-2019 relative reduction in age 18+ prevalence from the Annual Population Survey (males 27.5%) with the model-predicted No-NVP reduction (males 7.3%), the implied NVP-attributable relative reduction in adult smoking prevalence was 20.2% (95% CI, 18.8%-22.0%) for males and 20.4% (18.7%-22.2%) for females. The NVP-attributable reduction was 27.2% (22.8%-31.6%) for males and 31.7% (27.4%-36.5%) for females ages 18-24 and 18.6% (15.2%-21.8%) for males and 15.0% (11.1%-18.8%) for females ages 25-34, with similar reductions for ages 35 and above. The implied reduction in smoking prevalence between 2012 and 2019 equates to 165,660 (132,453-199,501) averted deaths by 2052. Other surveys yielded smaller, but relatively consistent results. CONCLUSIONS: An indirect method of simulation modeling indicates that substantial reductions in smoking prevalence occurred in England from 2012 to 2019 coinciding with the growth in nicotine vaping product use