Cross-Sectional Associations between Prenatal Per- and Poly-Fluoroalkyl Substances and Bioactive Lipids in Three Environmental Influences on Child Health Outcomes (ECHO) Cohorts.

Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipids─metabolic and inflammation pathway indicators. We estimated associations between prenatal PFAS exposure and bioactive lipids, measuring 12 serum PFAS and 50 plasma bioactive lipids in 414 pregnant women (median 17.4 weeks' gestation) from three Environmental influences on Child Health Outcomes Program cohorts. Pairwise association estimates across cohorts were obtained through linear mixed models and meta-analysis, adjusting the former for false discovery rates. Associations between the PFAS mixture and bioactive lipids were estimated using quantile g-computation. Pairwise analyses revealed bioactive lipid levels associated with PFDeA, PFNA, PFOA, and PFUdA (p < 0.05) across three enzymatic pathways (cyclooxygenase, cytochrome p450, lipoxygenase) in at least one combined cohort analysis, and PFOA and PFUdA (q < 0.2) in one linear mixed model. The strongest signature revealed doubling in PFOA corresponding with PGD2 (cyclooxygenase pathway; +24.3%, 95% CI: 7.3-43.9%) in the combined cohort. Mixture analysis revealed nine positive associations across all pathways with the PFAS mixture, the strongest signature indicating a quartile increase in the PFAS mixture associated with PGD2 (+34%, 95% CI: 8-66%), primarily driven by PFOS. Bioactive lipids emerged as prenatal PFAS exposure biomarkers, deepening insights into PFAS' influence on pregnancy outcomes.

Joint Asian Pacific Association of Gastroenterology (APAGE)-Asian Pacific Society of Digestive Endoscopy (APSDE) clinical practice guidelines on the use of non-invasive biomarkers for diagnosis of colorectal neoplasia.

Screening for colorectal cancer (CRC) is effective in reducing CRC related mortality. Current screening methods include endoscopy based and biomarker based approaches. This guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society of Digestive Endoscopy (APSDE), developed in response to the increasing use of, and accumulating supportive evidence for the role of, non-invasive biomarkers for the diagnosis of CRC and its precursor lesions. A systematic review of 678 publications and a two stage Delphi consensus process involving 16 clinicians in various disciplines was undertaken to develop 32 evidence based and expert opinion based recommendations for the use of faecal immunochemical tests, faecal based tumour biomarkers or microbial biomarkers, and blood based tumour biomarkers for the detection of CRC and adenoma. Comprehensive up-to-date guidance is provided on indications, patient selection and strengths and limitations of each screening tool. Future research to inform clinical applications are discussed alongside objective measurement of research priorities. This joint APAGE-APSDE practice guideline is intended to provide an up-to-date guide to assist clinicians worldwide in utilising non-invasive biomarkers for CRC screening; it has particular salience for clinicians in the Asia-Pacific region.

Diagnostic routes and time intervals for ovarian cancer in nine international jurisdictions; findings from the International Cancer Benchmarking Partnership (ICBP).

BACKGROUND: International Cancer Benchmarking Partnership Module 4 reports the first international comparison of ovarian cancer (OC) diagnosis routes and intervals (symptom onset to treatment start), which may inform previously reported variations in survival and stage. METHODS: Data were collated from 1110 newly diagnosed OC patients aged >40 surveyed between 2013 and 2015 across five countries (51-272 per jurisdiction), their primary-care physicians (PCPs) and cancer treatment specialists, supplement by treatment records or clinical databases. Diagnosis routes and time interval differences using quantile regression with reference to Denmark (largest survey response) were calculated. RESULTS: There were no significant jurisdictional differences in the proportion diagnosed with symptoms on the Goff Symptom Index (53%; P = 0.179) or National Institute for Health and Care Excellence NG12 guidelines (62%; P = 0.946). Though the main diagnosis route consistently involved primary-care presentation (63-86%; P = 0.068), onward urgent referral rates varied significantly (29-79%; P < 0.001). In most jurisdictions, diagnostic intervals were generally shorter and other intervals, in particular, treatment longer compared to Denmark. CONCLUSION: This study highlights key intervals in the diagnostic pathway where improvements could be made. It provides the opportunity to consider the systems and approaches across different jurisdictions that might allow for more timely ovarian cancer diagnosis and treatment.

Development of platforms for functional characterization and production of phenazines using a multi-chassis approach via CRAGE.

Phenazines (Phzs), a family of chemicals with a phenazine backbone, are secondary metabolites with diverse properties such as antibacterial, anti-fungal, or anticancer activity. The core derivatives of phenazine, phenazine-1-carboxylic acid (PCA) and phenazine-1,6-dicarboxylic acid (PDC), are themselves precursors for various other derivatives. Recent advances in genome mining tools have enabled researchers to identify many biosynthetic gene clusters (BGCs) that might produce novel Phzs. To characterize the function of these BGCs efficiently, we performed modular construct assembly and subsequent multi-chassis heterologous expression using chassis-independent recombinase-assisted genome engineering (CRAGE). CRAGE allowed rapid integration of a PCA BGC into 23 diverse γ-proteobacteria species and allowed us to identify top PCA producers. We then used the top five chassis hosts to express four partially refactored PDC BGCs. A few of these platforms produced high levels of PDC. Specifically, Xenorhabdus doucetiae and Pseudomonas simiae produced PDC at a titer of 293 mg/L and 373 mg/L, respectively, in minimal media. These titers are significantly higher than those previously reported. Furthermore, selectivity toward PDC production over PCA production was improved by up to 9-fold. The results show that these strains are promising chassis for production of PCA, PDC, and their derivatives, as well as for function characterization of Phz BGCs identified via bioinformatics mining.

Understanding patient barriers and facilitators to uptake of lung screening using low dose computed tomography: a mixed methods scoping review of the current literature.

BACKGROUND: Targeted lung cancer screening is effective in reducing mortality by upwards of twenty percent. However, screening is not universally available and uptake is variable and socially patterned. Understanding screening behaviour is integral to designing a service that serves its population and promotes equitable uptake. We sought to review the literature to identify barriers and facilitators to screening to inform the development of a pilot lung screening study in Scotland. METHODS: We used Arksey and O'Malley's scoping review methodology and PRISMA-ScR framework to identify relevant literature to meet the study aims. Qualitative, quantitative and mixed methods primary studies published between January 2000 and May 2021 were identified and reviewed by two reviewers for inclusion, using a list of search terms developed by the study team and adapted for chosen databases. RESULTS: Twenty-one articles met the final inclusion criteria. Articles were published between 2003 and 2021 and came from high income countries. Following data extraction and synthesis, findings were organised into four categories: Awareness of lung screening, Enthusiasm for lung screening, Barriers to lung screening, and Facilitators or ways of promoting uptake of lung screening. Awareness of lung screening was low while enthusiasm was high. Barriers to screening included fear of a cancer diagnosis, low perceived risk of lung cancer as well as practical barriers of cost, travel and time off work. Being health conscious, provider endorsement and seeking reassurance were all identified as facilitators of screening participation. CONCLUSIONS: Understanding patient reported barriers and facilitators to lung screening can help inform the implementation of future lung screening pilots and national lung screening programmes.

Verbal fluency as a quick and simple tool to help in deciding when to refer patients with a possible brain tumour.

BACKGROUND: Patients with brain tumours often present with non-specific symptoms. Correctly identifying who to prioritise for urgent brain imaging is challenging. Brain tumours are amongst the commonest cancers diagnosed as an emergency presentation. A verbal fluency task (VFT) is a rapid triage test affected by disorders of executive function, language and processing speed. We tested whether a VFT could support identification of patients with a brain tumour. METHODS: This proof-of-concept study examined whether a VFT can help differentiate patients with a brain tumour from those with similar symptoms (i.e. headache) without a brain tumour. Two patient populations were recruited, (a) patients with known brain tumour, and (b) patients with headache referred for Direct-Access Computed-Tomography (DACT) from primary care with a suspicion of a brain tumour. Semantic and phonemic verbal fluency data were collected prospectively. RESULTS: 180 brain tumour patients and 90 DACT patients were recruited. Semantic verbal fluency score was significantly worse for patients with a brain tumour than those without (P < 0.001), whether comparing patients with headache, or patients without headache. Phonemic fluency showed a similar but weaker difference. Raw and incidence-weighted positive and negative predictive values were calculated. CONCLUSION: We have demonstrated the potential role of adding semantic VFT score performance into clinical decision making to support triage of patients for urgent brain imaging. A relatively small improvement in the true positive rate in patients referred for DACT has the potential to increase the timeliness and efficiency of diagnosis and improve patient outcomes.

Patient-reported diagnostic intervals to colorectal cancer diagnosis in the Midland region of New Zealand: a prospective cohort study.

BACKGROUND AND OBJECTIVES: New Zealand (NZ) has high rates of colorectal cancer (CRC) but low rates of early detection. The majority of CRC is diagnosed through general practice, where lengthy diagnostic intervals are common. We investigated factors contributing to diagnostic delay in a cohort of patients newly diagnosed with CRC. METHODS: Patients were recruited from the Midland region and interviewed about their diagnostic experience using a questionnaire based on a modified Model of Pathways to Treatment framework and SYMPTOM questionnaire. Descriptive statistics were used to describe the population characteristics. Chi-square analysis and logistic regression were used to analyse factors influencing diagnostic intervals. RESULTS: Data from 176 patients were analysed, of which 65 (36.9%) experienced a general practitioner (GP) diagnostic interval of >120 days and 96 (54.5%) experienced a total diagnostic interval (TDI) > 120 days. Patients reporting rectal bleeding were less likely to experience a long TDI (odds ratio [OR] 0.34, 95% confidence interval [CI]: 0.14-0.78) and appraisal/help-seeking interval (OR, 0.19, 95% CI: 0.06-0.59). Patients <60 were more likely to report a longer appraisal/help-seeking interval (OR, 3.32, 95% CI: 1.17-9.46). Female (OR, 2.19, 95% CI: 1.08-4.44) and Maori patients (OR, 3.18, 95% CI: 1.04-9.78) were more likely to experience a long GP diagnostic interval. CONCLUSION: NZ patients with CRC can experience long diagnostic intervals, attributed to patient and health system factors. Young patients, Maori, females, and patients experiencing change of bowel habit may be at particular risk. We need to increase symptom awareness of CRC for patients and GPs. Concentrated efforts are needed to ensure equity for Maori in access to screening, diagnostics, and treatment.

New Zealand has high rates of colorectal cancer but low rates of early detection. We interviewed newly diagnosed patients about their diagnostic experience to identify factors influencing time to diagnosis. More than half of patients experienced a long diagnostic interval. Young patients, Maori, females, and patients experiencing changes of bowel habit may be at particular risk for long intervals. With the diagnostic difficulty of colorectal cancer (CRC), we need to increase CRC symptom awareness for patients and general practitioners.

Optimizing the implementation of lung cancer screening in Scotland: Focus group participant perspectives in the LUNGSCOT study.

INTRODUCTION: Targeted lung cancer screening is effective in reducing lung cancer and all-cause mortality according to major trials in the United Kingdom and Europe. However, the best ways of implementing screening in local communities requires an understanding of the population the programme will serve. We undertook a study to explore the views of those potentially eligible for, and to identify potential barriers and facilitators to taking part in, lung screening, to inform the development of a feasibility study. METHODS: Men and women aged 45-70, living in urban and rural Scotland, and either self-reported people who smoke or who recently quit, were invited to take part in the study via research agency Taylor McKenzie. Eleven men and 14 women took part in three virtual focus groups exploring their views on lung screening. Focus group transcripts were transcribed and analysed using thematic analysis, assisted by QSR NVivo. FINDINGS: Three overarching themes were identified: (1) Knowledge, awareness and acceptability of lung screening, (2) Barriers and facilitators to screening and (3) Promoting screening and implementation ideas. Participants were largely supportive of lung screening in principle and described the importance of the early detection of cancer. Emotional and psychological concerns as well as system-level and practical issues were discussed as posing barriers and facilitators to lung screening. CONCLUSIONS: Understanding the views of people potentially eligible for a lung health check can usefully inform the development of a further study to test the feasibility and acceptability of lung screening in Scotland. PATIENT OR PUBLIC CONTRIBUTION: The LUNGSCOT study has convened a patient advisory group to advise on all aspects of study development and implementation. Patient representatives commented on the focus group study design, study materials and ethics application, and two representatives read the focus group transcripts.

Acceptability of and barriers to human papillomavirus vaccination in China: A systematic review of the Chinese and English scientific literature.

INTRODUCTION: Widespread adoption of the human papillomavirus (HPV) vaccine will require population acceptance and tailoring of immunisation services to community needs and preferences. We examined peer-reviewed publications on the acceptability of and barriers to the HPV vaccine across China. METHODS: We searched English (MEDLINE, Embase, and Web of Science) and Chinese (CNKI, VIP, Wanfang data) databases between 1 January 2006 and 31 December 2017. We adopted a narrative approach for data synthesis. RESULTS: We identified 73 studies. The overall median acceptability of HPV vaccine was 71.8% (Q1-Q3: 58.6%-81%). Low levels of acceptability (<40%) of HPV vaccine were found in eastern regions of China. The largest differences of acceptability were observed between rural western regions (all >90%) and urban eastern regions (all <35%). Despite these regional variations, common barriers to HPV vaccine acceptance were concerns about vaccine safety, uncertainty over vaccine effectiveness, low perceived risk of cervical cancer and the price of the vaccine. The level of willingness to pay for the HPV vaccine (over 153 US dollars) was very low (<7%). CONCLUSION: The acceptability of and attitudes towards HPV vaccine vary by regions and populations across China. HPV vaccination programmes will need to tailor service delivery as well as information materials to take account of regional concerns.

Functional Analysis of Phenazine Biosynthesis Genes in Burkholderia spp.

Burkholderia encompasses a group of ubiquitous Gram-negative bacteria that includes numerous saprophytes as well as species that cause infections in animals, immunocompromised patients, and plants. Some species of Burkholderia produce colored, redox-active secondary metabolites called phenazines. Phenazines contribute to competitiveness, biofilm formation, and virulence in the opportunistic pathogen Pseudomonas aeruginosa, but knowledge of their diversity, biosynthesis, and biological functions in Burkholderia is lacking. In this study, we screened publicly accessible genome sequence databases and identified phenazine biosynthesis genes in multiple strains of the Burkholderia cepacia complex, some isolates of the B. pseudomallei clade, and the plant pathogen B. glumae We then focused on B. lata ATCC 17760 to reveal the organization and function of genes involved in the production of dimethyl 4,9-dihydroxy-1,6-phenazinedicarboxylate. Using a combination of isogenic mutants and plasmids carrying different segments of the phz locus, we characterized three novel genes involved in the modification of the phenazine tricycle. Our functional studies revealed a connection between the presence and amount of phenazines and the dynamics of biofilm growth in flow cell and static experimental systems but at the same time failed to link the production of phenazines with the capacity of Burkholderia to kill fruit flies and rot onions.IMPORTANCE Although the production of phenazines in Burkholderia was first reported almost 70 years ago, the role these metabolites play in the biology of these economically important microorganisms remains poorly understood. Our results revealed that the phenazine biosynthetic pathway in Burkholderia has a complex evolutionary history, which likely involved horizontal gene transfers among several distantly related groups of organisms. The contribution of phenazines to the formation of biofilms suggests that Burkholderia, like fluorescent pseudomonads, may benefit from the unique redox-cycling properties of these versatile secondary metabolites.

Patient and GP experiences of pathways to diagnosis of a second primary cancer: a qualitative study.

BACKGROUND: More people are surviving a first primary cancer and experiencing a second, different cancer. However, little is known about the diagnostic journeys of patients with second primary cancer (SPC). This study explores the views of patients and general practitioners (GPs) on their experiences of pathways to diagnosis of SPC, including the influence of a previous diagnosis of cancer on symptom appraisal, help-seeking and referral decisions. METHODS: Qualitative interviews with patients with a SPC diagnosis and case-linked GP interviews in a Scottish primary care setting. In-depth face to face or telephone interviews were conducted, underpinned by a social constructionist approach. Interviews were transcribed and Braun and Clarke's thematic analysis undertaken. Three analysts from the research team read transcripts and developed the coding framework using QSR NVivo version 10, with input from a fourth researcher. Themes were developed from refined codes and interpreted in the context of existing literature and theory. RESULTS: Interviews were conducted with 23 patients (aged 43-84 years) with a SPC diagnosis, and 7 GPs. Five patient themes were identified: Awareness of SPC, symptom appraisal and help-seeking, pathways to diagnosis, navigating the healthcare system, and impact of SPC. GPs interviews identified: experience and knowledge of SPC and referrals and decision-making. CONCLUSIONS: Insights into the pathway to diagnosis of SPC highlights the need for increased awareness of and vigilance for SPC among patients and healthcare providers (HCPs), and emotional support to manage the psychosocial burden.

Heterogeneity in colorectal cancer incidence among people recommended 3-yearly surveillance post-polypectomy: a validation study.

BACKGROUND: Colonoscopy surveillance is recommended for patients at increased risk of colorectal cancer (CRC) following adenoma removal. Low-, intermediate-, and high-risk groups are defined by baseline adenoma characteristics. We previously examined intermediate-risk patients from hospital data and identified a higher-risk subgroup who benefited from surveillance and a lower-risk subgroup who may not require surveillance. This study explored whether these findings apply in individuals undergoing CRC screening. METHODS: This retrospective study used data from the UK Flexible Sigmoidoscopy Screening Trial (UKFSST), English CRC screening pilot (ECP), and US Kaiser Permanente CRC prevention program (KPCP). Screening participants (50 - 74 years) classified as intermediate-risk at baseline colonoscopy were included. CRC data were available through 2006 (KPCP) or 2014 (UKFSST, ECP). Lower- and higher-risk subgroups were defined using our previously identified baseline risk factors: higher-risk participants had incomplete colonoscopies, poor bowel preparation, adenomas ≥ 20 mm or with high-grade dysplasia, or proximal polyps. We compared CRC incidence in these subgroups and in the presence vs. absence of surveillance using Cox regression. RESULTS: Of 2291 intermediate-risk participants, 45 % were classified as higher risk. Median follow-up was 11.8 years. CRC incidence was higher in the higher-risk than lower-risk subgroup (hazard ratio [HR] 2.08, 95 % confidence interval [CI] 1.07 - 4.06). Surveillance reduced CRC incidence in higher-risk participants (HR 0.35, 95 %CI 0.14 - 0.86) but not statistically significantly so in lower-risk participants (HR 0.41, 95 %CI 0.12 - 1.38). CONCLUSION: As previously demonstrated for hospital patients, screening participants classified as intermediate risk comprised two risk subgroups. Surveillance clearly benefited the higher-risk subgroup.

Rhizosphere plant-microbe interactions under water stress.

Climate change, with its extreme temperature, weather and precipitation patterns, is a major global concern of dryland farmers, who currently meet the challenges of climate change agronomically and with growth of drought-tolerant crops. Plants themselves compensate for water stress by modifying aerial surfaces to control transpiration and altering root hydraulic conductance to increase water uptake. These responses are complemented by metabolic changes involving phytohormone network-mediated activation of stress response pathways, resulting in decreased photosynthetic activity and the accumulation of metabolites to maintain osmotic and redox homeostasis. Phylogenetically diverse microbial communities sustained by plants contribute to host drought tolerance by modulating phytohormone levels in the rhizosphere and producing water-sequestering biofilms. Drylands of the Inland Pacific Northwest, USA, illustrate the interdependence of dryland crops and their associated microbiota. Indigenous Pseudomonas spp. selected there by long-term wheat monoculture suppress root diseases via the production of antibiotics, with soil moisture a critical determinant of the bacterial distribution, dynamics and activity. Those pseudomonads producing phenazine antibiotics on wheat had more abundant rhizosphere biofilms and provided improved tolerance to drought, suggesting a role of the antibiotic in alleviation of drought stress. The transcriptome and metabolome studies suggest the importance of wheat root exudate-derived osmoprotectants for the adaptation of these pseudomonads to the rhizosphere lifestyle and support the idea that the exchange of metabolites between plant roots and microorganisms profoundly affects and shapes the belowground plant microbiome under water stress.

Outcomes from colonoscopy following referral from New Zealand general practice: a retrospective analysis.

BACKGROUND: New Zealand has high rates of colorectal cancer (CRC) but poor outcomes. Most patients with CRC are diagnosed following referral from general practice, where a general practitioner (GP) assesses symptoms according to national guidelines. All referred patients are then re-prioritised by the hospital system. The first objective of this study was to identify what proportion of patients referred by general practice to surgical/gastroenterology at Waikato District Health Board (DHB) had a colonoscopy. The second objective was to determine what proportion of these referrals have an underlying CRC and the factors associated with the likelihood of this diagnosis. METHODS: This study is a retrospective analysis of e-referral data for patients aged 30-70+ who were referred from 75 general practices to general surgery, gastroenterology or direct to colonoscopy at Waikato DHB, 01 January 2015-31 December 2017. Primary and secondary outcome measures included the proportion and characteristics of patients who were having colonoscopy, and of those, who were diagnosed with CRC. Data were analysed using chi square and logistic regression. RESULTS: 6718/20648 (32.5%) patients had a colonoscopy and 372 (5.5%) of these were diagnosed with CRC. The probability of having CRC following a colonoscopy increased with age (p value < 0.001). Females (p value < 0.001), non-Maori (p value < 0.001), and patients with a high suspicion of cancer (HSCan) label originating from their GP were more likely to have a colonoscopy, while the odds ratio of Maori having a colonoscopy was 0.66 (95% CI 0.60-0.73). The odds ratio of a CRC diagnosis following colonoscopy was 1.67 (95% CI 1.35-2.07) for men compared to women, and 2.34 (95% CI 1.70-3.22) for those with a GP HSCan label. Of the 585 patients referred with a GP HSCan, 423 (72.3%) were reprioritised by the hospital and 55 patients had their diagnosis unnecessarily delayed. CONCLUSIONS: If a GP refers a patient with an HSCan, and the patient receives a colonoscopy, then the likelihood of having CRC is almost 15.0%. This would suggest that these patients should be routinely prioritised without further triage by the hospital. Further research is needed to understand why Maori are less likely to receive a colonoscopy following referral from general practice.

Evaluation of the Phytotoxicity of 2,4-Diacetylphloroglucinol and Pseudomonas brassicacearum Q8r1-96 on Different Wheat Cultivars.

Pseudomonas brassicacearum Q8r1-96 and other 2,4-diacetylphloroglucinol (DAPG)-producing pseudomonads of the P. fluorescens complex possess both biocontrol and growth-promoting properties and play an important role in suppression of take-all of wheat in the Pacific Northwest (PNW) of the United States. However, P. brassicacearum can also reduce seed germination and cause root necrosis on some wheat cultivars. We evaluated the effect of Q8r1-96 and DAPG on the germination of 69 wheat cultivars that have been or currently are grown in the PNW. Cultivars varied widely in their ability to tolerate P. brassicacearum or DAPG. The frequency of germination of the cultivars ranged from 0 to 0.87 and 0.47 to 0.90 when treated with Q8r1-96 and DAPG, respectively. There was a significant positive correlation between the frequency of germination of cultivars treated with Q8r1-96 in assays conducted in vitro and in the greenhouse. The correlation was greater for spring than for winter cultivars. In contrast, the effect of Q8r1-96 on seed germination was not correlated with that of DAPG alone, suggesting that DAPG is not the only factor responsible for the phytotoxicity of Q8r1-96. Three wheat cultivars with the greatest tolerance and three cultivars with the least tolerance to Q8r1-96 were tested for their ability to support root colonization by strain Q8r1-96. Cultivars with the greatest tolerance supported significantly greater populations of strain Q8r1-96 than those with the least tolerance to the bacteria. Our results show that wheat cultivars differ widely in their interaction with P. brassicacearum and the biocontrol antibiotic DAPG.

Proteomics Reveals the Changes that Contribute to Fusarium Head Blight Resistance in Wheat.

Fusarium head blight (FHB) is a devastating disease of wheat, causing yield losses and quality reduction as a result of mycotoxin production. In this study, iTRAQ (isobaric tags for relative and absolute quantification)-labeling-based mass spectrometry was employed to characterize the proteome in wheat cultivars Xinong 538 and Zhoumai 18 with contrasting levels of FHB resistance as a means to elucidate the molecular mechanisms contributing to FHB resistance. A total of 13,669 proteins were identified in the two cultivars 48 h after Fusarium graminearum inoculation. Among these, 2,505 unique proteins exclusively accumulated in Xinong 538 (resistant) and 887 proteins in Zhoumai 18 (susceptible). Gene Ontology enrichment analysis showed that most differentially accumulated proteins (DAPs) from both cultivars were assigned to the following categories: metabolic process, single-organism process, cellular process, and response to stimulus. Kyoto Encyclopedia of Genes and Genomes analysis showed that a greater number of proteins belonging to different metabolic pathways were identified in Xinong 538 compared with Zhoumai 18. Specifically, DAPs from the FHB-resistant cultivar Xinong 538 populated categories of metabolic pathways related to plant-pathogen interaction. These DAPs might play a critical role in defense responses exhibited by Xinong 538. DAPs from both genotypes were assigned to all wheat chromosomes except chromosome 6B, with approximately 30% mapping to wheat chromosomes 2B, 3B, 5B, and 5D. Twenty single nucleotide polymorphism markers, flanking DAPs on chromosomes 1B, 3B, 5B, and 6A, overlapped with the location of earlier mapped FHB-resistance quantitative trait loci. The data provide evidence for the involvement of several DAPs in the early stages of the FHB-resistance response in wheat; however, further functional characterization of candidate proteins is warranted.

Experiences of cervical screening participation and non-participation in women from minority ethnic populations in Scotland.

BACKGROUND: The introduction of screening in the UK and other high-income countries led to a significant decrease in the incidence of cervical cancer and increase in survival rates. Minority ethnic groups are often underrepresented in screening participation for reasons that are poorly understood. OBJECTIVE: To explore experiences of cervical screening participation and non-participation of women from minority ethnic populations in Scotland and gain insights to support the development of interventions that could potentially support screening participation and thereby reduce inequalities. DESIGN: Qualitative comparison group study using in-depth, semi-structured individual interviews that were thematically analysed. SETTING AND PARTICIPANTS: This study took place in Scotland. Fifty women were purposively sampled from four ethnic minority groups: South Asian; East European; Chinese; and Black African or Caribbean. White Scottish women were also interviewed. RESULTS: Many experiences described were common regardless of ethnicity, such as difficulties managing competing priorities, including work and care responsibilities. However, important differences existed across the groups. These included going abroad for more frequent screening, delayed introduction to screening and not accessing primary care services, language difficulties in health-care settings despite proficiency in English and not being sexually active at screening commencement. Experiences of racism, ignorance and feeling shamed were also reported. CONCLUSIONS: Key differences exist in the experience of minority ethnic groups in Scotland. These offer potential opportunities to reduce disparity and support screening participation including maximizing co-incidental interactions and developing outreach work.

Economic evaluation of GPs' direct access to computed tomography for identification of brain tumours.

BACKGROUND: When GPs suspect a brain tumour, a referral for specialist assessment and subsequent brain imaging is generally the first option. NICE has recommended that GPs have rapid direct access to brain imaging for adults with progressive sub-acute loss of central nervous function; however, no studies have evaluated the cost-effectiveness. METHODS: We developed a cost-effectiveness model based on data from one region of the UK with direct access computed tomography (DACT), routine data from GP records and the literature, to explore whether unrestricted DACT for patients with suspected brain tumour might be more cost-effective than criteria-based DACT or no DACT. RESULTS: Although criteria-based DACT allows some patients without brain tumour to avoid imaging, our model suggests this may increase costs of diagnosis due to non-specific risk criteria and high costs of diagnosing or 'ruling out' brain tumours by other pathways. For patients diagnosed with tumours, differences in outcomes between the three diagnostic strategies are small. CONCLUSIONS: Unrestricted DACT may reduce diagnostic costs; however, the evidence is not strong and further controlled studies are required. Criteria-based access to CT for GPs might reduce demand for DACT, but imperfect sensitivity and specificity of current risk stratification mean that it will not necessarily be cost-effective.

How do colorectal cancer patients rate their GP: a mixed methods study.

BACKGROUND: New Zealand (NZ) has a high incidence of colorectal cancer (CRC) and low rates of early diagnosis. With screening not yet nationwide, the majority of CRC is diagnosed through general practice. A good patient-general practitioner (GP) relationship can facilitate prompt diagnosis, but when there is a breakdown in this relationship, delays can occur. Delayed diagnosis of CRC in NZ receives a disproportionally high number of complaints directed against GPs, suggesting deficits in the patient-GP connection. We aimed to investigate patient-reported confidence and ratings of their GP following the diagnostic process. METHODS: This study is a mixed methods analysis of responses to a structured questionnaire and free text comments from patients newly diagnosed with CRC in the Midland region of NZ. A total of 195 patients responded to the structured questionnaire, and 113 patients provided additional free text comments. Descriptive statistics were used to describe the study population and chi square analysis determined the statistical significance of factors possibly linked to delay. Free text comments were analysed using a thematic framework. RESULTS: Most participants rated their GP as 'Very good/Good' at communication with patients about their health conditions and involving them in decisions about their care, and 6.7% of participants rated their overall level of confidence and trust in their GP as 'Not at all'. Age, gender, ethnicity and a longer diagnostic interval were associated with lower confidence and trust. Free text comments were grouped in to three themes: 1. GP Interpersonal skills; (communication, listening, taking patient symptoms seriously), 2. Technical competence; (speed of referral, misdiagnoses, lack of physical examination), and 3. Organisation of general practice care; (appointment length, getting an appointment, continuity of care). CONCLUSIONS: Maori, females, and younger participants were more likely to report low confidence and trust in their GP. Participants associate a poor diagnostic experience with deficits in the interpersonal and technical skills of their GP, and health system factors within general practice. Short appointment times, access to appointments and poor GP continuity are important components of how patients assess their experience and are particularly important to ensure equal access for Maori patients.

Symptoms and signs of colorectal cancer, with differences between proximal and distal colon cancer: a prospective cohort study of diagnostic accuracy in primary care.

BACKGROUND: In an abdominal symptom study in primary care in six European countries, 511 cases of cancer were recorded prospectively among 61,802 patients 16 years and older in Norway, Denmark, Sweden, Netherlands, Belgium and Scotland. Colorectal cancer is one of the main types of cancer associated with abdominal symptoms; hence, an in-depth subgroup analysis of the 94 colorectal cancers was carried out in order to study variation in symptom presentation among cancers in different anatomical locations. METHOD: Initial data capture was by completion of standardised forms containing closed questions about symptoms recorded during the consultation. Follow-up data were provided by the GP after diagnosis, based on medical record data made after the consultation. GPs also provided free text comments about the diagnostic procedure for individual patients. Fisher's exact test was used to analyse differences between groups. RESULTS: Almost all symptoms recorded could indicate colorectal cancer. 'Rectal bleeding' had a specificity of 99.4% and a PPV of 4.0%. Faecal occult blood in stool (FOBT) or anaemia may indicate gastrointestinal bleeding: when these symptoms and signs were combined, sensitivity reached 57.5%, with 69.2% for cancer in the distal colon. For proximal colon cancers, none of 18 patients had 'Rectal bleeding' at the initial consultation, but three of the 18 did so at a later consultation. 'Abdominal pain, lower part', 'Constipation' and 'Distended abdomen, bloating' were less specific and also less sensitive than 'Rectal bleeding', and with PPV between 0.7% and 1.9%. CONCLUSIONS: Apart from rectal bleeding, single symptoms did not reach the PPV 3% NICE threshold. However, supplementary information such as a positive FOBT or persistent symptoms may revise the PPV upwards. If a colorectal cancer is suspected by the GP despite few symptoms, the total clinical picture may still reach the NICE PPV threshold of 3% and justify a specific referral.