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The development of the microbiome from infancy to childhood is dependent on a range of factors, with microbial-immune crosstalk during this time thought to be involved in the pathobiology of later life diseases 1-9 such as persistent islet autoimmunity and type 1 diabetes 10-12 . However, to our knowledge, no studies have performed extensive characterization of the microbiome in early life in a large, multi-centre population. Here we analyse longitudinal stool samples from 903 children between 3 and 46 months of age by 16S rRNA gene sequencing (n = 12,005) and metagenomic sequencing (n = 10,867), as part of the The Environmental Determinants of Diabetes in the Young (TEDDY) study. We show that the developing gut microbiome undergoes three distinct phases of microbiome progression: a developmental phase (months 3-14), a transitional phase (months 15-30), and a stable phase (months 31-46). Receipt of breast milk, either exclusive or partial, was the most significant factor associated with the microbiome structure. Breastfeeding was associated with higher levels of Bifidobacterium species (B. breve and B. bifidum), and the cessation of breast milk resulted in faster maturation of the gut microbiome, as marked by the phylum Firmicutes. Birth mode was also significantly associated with the microbiome during the developmental phase, driven by higher levels of Bacteroides species (particularly B. fragilis) in infants delivered vaginally. Bacteroides was also associated with increased gut diversity and faster maturation, regardless of the birth mode. Environmental factors including geographical location and household exposures (such as siblings and furry pets) also represented important covariates. A nested case-control analysis revealed subtle associations between microbial taxonomy and the development of islet autoimmunity or type 1 diabetes. These data determine the structural and functional assembly of the microbiome in early life and provide a foundation for targeted mechanistic investigation into the consequences of microbial-immune crosstalk for long-term health.

Objectives: The composition and structure of site-specific microbiota have been investigated as potential biomarkers for a variety of chronic inflammatory diseases and cancers. While many studies have focused on the changes in the airway microbiota using respiratory specimens from patients with various respiratory diseases, more research is needed to explore the microbial profiles within the distal lung parenchyma in smokers with lung cancer and/or emphysema., Materials and Methods: To describe and contrast lung tissue-associated microbial signatures in smokers with lung cancer and/or emphysema, we employed culture-independent pyrosequencing of 16S rRNA gene hypervariable V4 region and compositional analysis in non-malignant lung tissue samples obtained from 40 heavy smokers, including 10 emphysema-only, 11 lung cancer-only, and 19 with both lung cancer and emphysema., Results and Conclusion: The emphysema-only group presented a lower bacterial community evenness defined by a significantly lower Shannon diversity index compared to the lung cancer patients with or without emphysema ( P = 0.006). Furthermore, community compositions of lung cancer patients with or without emphysema were characterized by a significantly lower abundance of Proteobacteria (primary the genera Acinetobacter and Acidovorax ) and higher prevalence of Firmicutes ( Streptococcus ) and Bacteroidetes ( Prevotella ), compared to emphysema-only patients. In conclusion, the lung microbial composition and communities structures of smokers with lung cancer are distinct from the emphysema-only patients. Although preliminary, our findings suggest that lung microbiome changes could be a biomarker of lung cancer that could eventually be used to help screening for the disease., Competing Interests: None.

[This corrects the article DOI: 10.7717/peerj.4693.].

Understanding how students interact and learn within the lecture theatre environment is central to successful learning outcomes. Previous studies into the use of the lecture theatre teaching space have found that students sit in specific locations due to a range of factors; these include being noticed, addressing anxiety or an ability to focus. This study further explores the personal and social factors at play within students' lecture theatre seating choice and the resulting effects on attainment. Student responses on seating preferences detailing why they chose a given location were mapped at a seat-specific level and correlated against attainment. In parallel, staff perceptions of student attainment in relation to their seating choice were obtained. No direct correlation between student location and attainment was found, contrary to staff perceptions. Interestingly, it was found that students physically locate into friendship groups clusters and that these clusters obtained similar levels of attainment in problem-solving tasks, with pockets of both high- and low-performing students being observed. It was also noted that isolated students performed less well. These data would indicate that peer group formation exerts a strong impact on attainment and engagement. Outcomes from this study will enable academic staff to better understand the student body and inform the way in which teaching sessions are performed within a lecture theatre.

Background: An elevated risk of suicide after a diagnosis of prostate cancer has been reported previously in the USA and Sweden. We aimed to identify whether prostate cancer survivors resident in New South Wales Australia are at higher risk of suicide and if so, who is most at risk., Methods: Data were obtained from the New South Wales (NSW) Cancer Registry for all men diagnosed with prostate cancer in NSW during 1997 to 2007. These were linked by the Centre for Health Record Linkage (CHeReL) to Australian Bureau of Statistics Mortality Data to the end of 2007 to determine vital status and cause of death. We compared the number of suicides observed for prostate cancer survivors with the expected number of suicides based on age- and calendar year- specific rates for the NSW male population using standardised mortality ratios (SMRs). Suicide rate ratios (RR) by disease and patients' characteristics were estimated using multivariable negative binomial regression to determine the most at risk groups., Results: During the study period 51,924 NSW men were diagnosed with prostate cancer. Forty nine of these men were subsequently recorded as committing suicide up to 10 years after diagnosis with an SMR of 1.70 (95% CI:1.26-2.25). Twenty six (53%) of these suicides occurred within 12 months after diagnosis. Risk diminished over time since diagnosis (RR in 1-2 years after diagnosis = 0.29, 95% CI: 0.12-0.71, 2-4 years RR = 0.30, 95% CI: 0.14-0.16 and 4+ years RR = 0.26, 95% CI: 0.11-0.60 compared with <1 year since diagnosis). Men with non-localised disease had a higher risk of suicide compared to men with localised disease (RR = 2.68, 95% CI: 1.15-6.23). Men living outside major cities had lower risk of suicide compared to those resident in major cities (rate ratio = 0.42, 95% CI: 0.20-0.87). Single, divorced, widowed or separated men were more likely to commit suicide than married men (RR = 4.18, 95% CI: 2.36-7.42)., Conclusion: Risk of suicide is higher for NSW men diagnosed with prostate cancer than the general age matched male population. Vulnerable or lonely men and those with pre-existing depression or suicidal ideation who are diagnosed with prostate cancer should be offered additional psychological support., Competing Interests: The authors have declared that no competing interests exist.

Background: Long-term psychological well-being and quality-of-life are important considerations when deciding whether to undergo active treatment for low-risk localised prostate cancer., Objective: To assess the long-term effects of active surveillance (AS) and/or watchful waiting (WW) on psychological and quality-of-life outcomes for low-risk localised prostate cancer patients., Design, Setting, and Participants: The Prostate Cancer Care and Outcome Study is a population-based prospective cohort study in New South Wales, Australia. Participants for these analyses were low-risk localised prostate cancer patients aged <70 yr at diagnosis and participated in the 10-yr follow-up., Outcome Measurements and Statistical Analysis: Validated instruments assessed outcomes relating to six health-related quality-of-life and nine psychological domains relevant to prostate cancer patients. Adjusted mean differences (AMDs) in outcome scores between prostate cancer treatment groups were estimated using linear regression., Results and Limitations: At 9-11 yr after diagnosis, patients who started AS/WW initially had (1) higher levels of distress and hyperarousal than initial radiation/high-dose-rate brachytherapy patients (AMD=5.9; 95% confidence interval or CI [0.5, 11.3] and AMD=5.4; 95% CI [0.2, 10.5], respectively), (2) higher levels of distress and avoidance than initial low-dose-rate brachytherapy patients (AMD=5.3; 95% CI [0.2, 10.3] and AMD=7.0; 95% CI [0.5, 13.5], respectively), (3) better urinary incontinence scores than initial radical prostatectomy patients (AMD=-9.1; 95% CI [-16.3, -2.0]), and (4) less bowel bother than initial radiation/high-dose-rate brachytherapy patients (AMD=-16.8; 95% CI [-27.6, -6.0]). No other significant differences were found. Limitations include participant attrition, inability to assess urinary voiding and storage symptoms, and nonrandom treatment allocation., Conclusions: Notwithstanding some long-term differences between AS/WW and various active treatment groups in terms of distress, hyperarousal, avoidance, urinary incontinence, and bowel bother, most long-term outcomes were similar between these groups., Patient Summary: This study assessed the long-term psychological and quality-of-life impacts of initially monitoring rather than actively treating low-risk prostate cancer. The results suggest that initial monitoring rather than active treatment has only a minor impact on subsequent long-term psychological and quality-of-life outcomes., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Emerging evidence suggests that a diagnosis of cutaneous melanoma (CM) may be associated with prostate cancer (PC) incidence. We examined if the incidence of CM was associated with an increased subsequent risk of PC. We used data from the New South Wales Cancer Registry for all CM and PC cases diagnosed between January 1972 and December 2008. We calculated the age standardized incidence ratio (SIR) and 95% confidence intervals (95% CI) for PC incidence following a CM diagnosis, applying age- and calendar- specific rates to the appropriate person years at risk. We determined rate ratio (RR) and 95% CI of PC incidence according to specified socio-demographic categories and disease related characteristics, using a negative binomial model. There were 143,594 men diagnosed with PC or CM in the study period and of these 101,198 and 42,396 were diagnosed with PC and CM, respectively, as first primary cancers. Risk of PC incidence increased following CM diagnosis (n = 2,114; SIR = 1.25; 95% CI:1.20.8-1.31: p < 0.0001), with the increased risk apparent in men diagnosed with localised CM (n = 1,862;SIR = 1.26; 95% CI:1.20-1.32). CM diagnosis increased the subsequent risk of PC incidence. This raises the potential for future PC risk to be discussed with newly diagnosed males with CM.

Background: The use of electronic cigarettes (ECs) has increased drastically over the past five years, primarily as an alternative to smoking tobacco cigarettes. However, the adverse effects of acute and long-term use of ECs on the microbiota have not been explored. In this pilot study, we sought to determine if ECs or tobacco smoking alter the oral and gut microbiota in comparison to non-smoking controls., Methods: We examined a human cohort consisting of 30 individuals: 10 EC users, 10 tobacco smokers, and 10 controls. We collected cross-sectional fecal, buccal swabs, and saliva samples from each participant. All samples underwent V4 16S rRNA gene sequencing., Results: Tobacco smoking had a significant effect on the bacterial profiles in all sample types when compared to controls, and in feces and buccal swabs when compared to EC users. The most significant associations were found in the gut, with an increased relative abundance of Prevotella ( P = 0.006) and decreased Bacteroides ( P = 0.036) in tobacco smokers. The Shannon diversity was also significantly reduced ( P = 0.009) in fecal samples collected from tobacco smokers compared to controls. No significant difference was found in the alpha diversity, beta-diversity or taxonomic relative abundances between EC users and controls., Discussion: From a microbial ecology perspective, the current pilot data demonstrate that the use of ECs may represent a safer alternative compared to tobacco smoking. However, validation in larger cohorts and greater understanding of the short and long-term impact of EC use on microbiota composition and function is warranted., Competing Interests: The authors declare that they have no competing interests.

The oral microbiome has been linked to a number of chronic inflammatory conditions, including obesity, diabetes, periodontitis, and cancers of the stomach and liver. These conditions disproportionately affect Mexican American women, yet few studies have examined the oral microbiota in this at-risk group. We characterized the 16S rDNA oral microbiome in 369 non-smoking women enrolled in the MD Anderson Mano a Mano Mexican American Cohort Study. Lower bacterial diversity, a potential indicator of oral health, was associated with increased age and length of US residency among recent immigrants. Grouping women by overarching bacterial community type (e.g., "Streptococcus," "Fusobacterium," and "Prevotella" clusters), we observed differences across a number of acculturation-related variables, including nativity, age at immigration, time in the US, country of longest residence, and a multi-dimensional acculturation scale. Participants in the cluster typified by higher abundance of Streptococcus spp. exhibited the lowest bacterial diversity and appeared the most acculturated as compared to women in the "Prevotella" group. Computationally-predicted functional analysis suggested the Streptococcus-dominated bacterial community had greater potential for carbohydrate metabolism while biosynthesis of essential amino acids and nitrogen metabolism prevailed among the Prevotella-high group. Findings suggest immigration and adaption to life in the US, a well-established mediator of disease risk, is associated with differences in oral microbial profiles in Mexican American women. These results warrant further investigation into the joint and modifying effects of acculturation and oral bacteria on the health of Mexican American women and other immigrant populations. The oral microbiome presents an easily accessible biomarker of disease risk, spanning biological, behavioral, and environmental factors.

Ryk is a member of the receptor tyrosine kinase (RTK) family of proteins that control and regulate cellular processes. It is distinguished by binding Wnt ligands and having no detectable intrinsic protein tyrosine kinase activity suggesting Ryk is a pseudokinase. Here, we show an essential role for Ryk in directing morphogenetic events required for normal cardiac development through the examination of Ryk-deficient mice. We employed vascular corrosion casting, vascular perfusion with contrast dye, and immunohistochemistry to characterize cardiovascular and pharyngeal defects in Ryk -/- embryos. Ryk -/- mice exhibit a variety of malformations of the heart and outflow tract that resemble human congenital heart defects. This included stenosis and interruption of the aortic arch, ventriculoarterial malalignment, ventricular septal defects and abnormal pharyngeal arch artery remodelling. This study therefore defines a key intersection between a subset of growth factor receptors involved in planar cell polarity signalling, the Wnt family and mammalian cardiovascular development.

Objective: Non-muscle invasive bladder cancer (NMIBC) is a chronic condition requiring ongoing treatment and endoscopic examinations that are frequent and can be life-long. To ensure the comprehensive assessment of the benefits and harms of treatments for NMIBC, the impact on important and relevant patient-reported outcomes (PROs) should be determined. We systematically reviewed the NMIBC PRO literature to determine the suitability of available PRO measures (PROMs) for use in evaluating patient outcomes in NMIBC research., Methods: We searched six electronic databases, reference lists, and key authors. Two reviewers independently applied inclusion and quality criteria and extracted findings. PROM domains, item content, and content coverage and relevance were determined for identified PROMs. Content validity was assessed against an empirically derived NMIBC-specific conceptual framework that includes 11 PRO domains and 19 sub-domains., Results: Seventeen studies assessed PROs related to NMIBC and treatment impact. From these studies, 11 PROMs were identified, including three generic, three cancer-specific, and five symptom-specific. None of the PROMs cover all PRO domains important in NMIBC as assessed against our conceptual framework. The EORTC QLQ-C30 plus the NMIBC24 module was best aligned to the conceptual model, but failed to represent six outcomes important to NMIBC patients., Conclusions: Currently, some outcomes important in NMIBC are inadequately covered by generic and cancer-specific measures despite similar conceptual models. This review identified gaps in the literature regarding assessment of symptoms and other PROs considered important by NMIBC patients. Careful consideration of PROM item content is required when selecting outcome measures for use in future NMIBC clinical trials to ensure that appropriate measures are used to assess outcomes that matter to patients.

Background: This study assessed whether a theoretically conceptualised tailored intervention centred on multidisciplinary teams (MDTs) increased clinician referral behaviours in line with clinical practice guideline recommendations., Methods: Nine hospital Sites in New South Wales (NSW), Australia with a urological MDT and involvement in a state-wide urological clinical network participated in this pragmatic stepped wedge, cluster randomised implementation trial. Intervention strategies included flagging of high-risk patients by pathologists, clinical leadership, education, and audit and feedback of individuals' and study Sites' practices. The primary outcome was the proportion of patients referred to radiation oncology within 4 months after prostatectomy. Secondary outcomes were proportion of patients discussed at a MDT meeting within 4 months after surgery; proportion of patients who consulted a radiation oncologist within 6 months; and the proportion who commenced radiotherapy within 6 months. Urologists' attitudes towards adjuvant radiotherapy were surveyed pre- and post-intervention. A process evaluation measured intervention fidelity, response to intervention components and contextual factors that impacted on implementation and sustainability., Results: Records for 1071 high-risk post-RP patients operated on by 37 urologists were reviewed: 505 control-phase; and 407 intervention-phase. The proportion of patients discussed at a MDT meeting increased from 17% in the control-phase to 59% in the intervention-phase (adjusted RR = 4.32; 95% CI [2.40 to 7.75]; p < 0·001). After adjustment, there was no significant difference in referral to radiation oncology (intervention 32% vs control 30%; adjusted RR = 1.06; 95% CI [0.74 to 1.51]; p = 0.879). Sites with the largest relative increases in the percentage of patients discussed also tended to have greater increases in referral (p = 0·001). In the intervention phase, urologists failed to provide referrals to more than half of patients whom the MDT had recommended for referral (78 of 140; 56%)., Conclusions: The intervention resulted in significantly more patients being discussed by a MDT. However, the recommendations from MDTs were not uniformly recorded or followed. Although practice varied markedly between MDTs, the intervention did not result in a significant overall change in referral rates, probably reflecting a lack of change in urologists' attitudes. Our results suggest that interventions focused on structures and processes that enable health system-level change, rather than those focused on individual-level change, are likely to have the greatest effect., Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12611001251910 ). Registered 6 December 2011.

Australia has one of the highest incidence rates of prostate cancer (PC) worldwide, due in part to widespread prostate specific antigen (PSA) testing. We aimed to identify factors associated with PSA testing in Australian men without a diagnosis of prostate cancer or prior prostate disease. Participants were men joining the 45 and Up Study in 2006-2009, aged ≥45 years at recruitment. Self-completed questionnaires were linked to cancer registrations, hospitalisations, health services data and deaths. Men with a history of PC, radical prostatectomy or a "monitoring" PSA test for prostate disease were excluded. We identified Medicare reimbursed PSA tests during 2012-2014. Multivariable logistic regression was used to estimate adjusted odds ratios (OR) for the association between having PSA tests and factors of interest. Of the 62,765 eligible men, 51.8% had at least one screening PSA test during 2012-2014. Factors strongly associated with having a PSA test included having 27+ general practitioner consultations (versus 3-9 consultations; OR = 2.00; 95%CI = 1.90-2.11), benign prostatic hyperplasia treatment (versus none; OR = 1.59(95%CI = 1.49-1.70), aged 60-69 years (versus 50-59 years; OR = 1.54; 95%CI = 1.48-1.60). These results emphasise the important role of primary care in decision making about PSA testing.

Background: Melanoma and prostate cancer may share risk factors. This study examined the association between serum PSA levels, which is a risk factor for prostate cancer, and variants in some melanoma-associated pigmentary genes., Methods: We studied participants, all aged 70+ years, in the Concord Health and Ageing in Men Project who had no history of prostatitis or received treatment for prostate disease (n = 1033). We genotyped variants in MC1R (rs1805007, rs1805008), ASIP (rs4911414, rs1015362), SLC45A2 (rs28777, rs16891982), IRF4 (rs12203592), TYRP1 (rs1408799), TYR (rs1126809, rs1042602), SLC24A2 (rs12896399), and OCA2 (rs7495174). Generalised linear dominant models with Poisson distribution, log link functions and robust variance estimators estimated adjusted percentage differences (%PSA) in mean serum PSA levels (ng/mL) between variant and wildtype (0%PSA = reference) genotypes, adjusting for age, body mass index, serum 25OHD levels and birth regions (Australia or New Zealand (ANZ), Europe or elsewhere)., Results: Serum PSA levels were strongly associated with advancing age and birth regions: mean PSA levels were lower in Europe-born (-29.7%) and elsewhere-born (-11.7%) men than ANZ-born men (reference). Lower %PSA was observed in men with variants in SLC45A2: rs28777 (-19.6;95%CI: -33.5, -2.7), rs16891982 (-17.3;95%CI:-30.4,-1.7) than in wildtype men (reference). There were significant interactions between birth regions and PSA levels in men with variants in MC1R (rs1805007; p-interaction = 0.0001) and ASIP (rs4911414; p-interaction = 0.007). For these genes %PSA was greater in ANZ-born men and lower in Europe- and elsewhere-born men with the variant than it was in wildtype men. In a post hoc analysis, serum testosterone levels were increased in men with MC1R rs1805007 and serum dihydrotestosterone in men with ASIP rs1015362., Conclusion: Men with SNPs in SLC45A2, who have less sun sensitive skin, have lower PSA levels. Men with SNPs in MC1R and ASIP, who have more sun sensitive skin, and were born in ANZ, have higher PSA levels. Androgens may modify these apparent associations of pigmentary genes and sun exposure with PSA levels., Impact: PSA levels and possibly prostate cancer risk may vary with sun sensitivity and sun exposure, the effects of which might be modified by androgen levels.

Objective: To assess whether the use of complementary and alternative medicines therapies (CAMs) for prostate cancer and/or its treatment side effects by long-term survivors is associated with selected socio-demographic, clinical, health-related quality-of-life (HRQOL) and/or psychological factors., Design, Setting and Participants: The Prostate Cancer Care and Outcomes Study (PCOS) is a population-based cohort study of men with prostate cancer who were aged less than 70 years at diagnosis in New South Wales, Australia. Included in these analyses were men who returned a 10-year follow-up questionnaire, which included questions about CAM use., Methods: Validated instruments assessed patient's HRQOL and psychological well-being. Poisson regression with robust variance estimation was used to estimate the adjusted relative risks of current CAM use for prostate cancer according to socio-demographic, clinical, HRQOL and psychological factors., Results: 996 of 1634 (61%) living PCOS participants completed the 10-year questionnaire. Of these 996 men, 168 (17%) were using CAMs for prostate cancer and 525 (53%) were using CAMs for any reason (including prostate cancer). Those using CAM for prostate cancer were more likely to be regular or occasional support group participants (vs. no participation RR = 2.02; 95%CI 1.41-2.88), born in another country (vs. Australian born RR = 1.59; 95%CI 1.17-2.16), have received androgen deprivation treatment (ADT) since diagnosis (RR = 1.60; 95%CI 1.12-2.28) or in the past two years (RR = 2.34; 95%CI 1.56-3.52). CAM use was associated with greater fear of recurrence (RR = 1.29; 95%CI 1.12-1.48), cancer-specific distress (RR = 1.15; 95%CI 1.01-1.30), cancer-specific hyperarousal (RR = 1.17; 95%CI 1.04-1.31), cancer locus of control (RR = 1.16; 95%CI 1.01-1.34) and less satisfaction with medical treatments (RR = 0.86; 95%CI 0.76-0.97), but not with intrusive thinking, cognitive avoidance, depression, anxiety or any HRQOL domains., Conclusions: In this study, about one in six long term prostate cancer survivors used CAMs for their prostate cancer with use centred around ADT, country of birth, distress, cancer control, fear of recurrence and active help seeking.

The purpose of this study was to provide in-depth insight into men's experiences of prostate cancer, specifically: perceived stigma and self-blame, social isolation, unmet need and help-seeking. A qualitative descriptive approach was used. Semi-structured interviews were undertaken with 20 men diagnosed with prostate cancer, and thematic analysis was undertaken. Some participants perceived a stigma associated with prostate cancer and cancer in general, which sometimes acted as a barrier to disclosure. Self-blame and internalisation of cause was not a prominent issue. Participants' descriptions of emotional distress, social isolation and anxiety demonstrated the impact of prostate cancer. Social isolation was most commonly reported as a physical consequence of treatment and/or side effects. Participants felt both support and ongoing care were limited at post-treatment. Most did not seek or receive help for emotional or psychosocial problems from a formal source due to anticipated awkwardness, autonomous coping, not burdening others, unwanted sympathy and retaining privacy. Prostate cancer can cause considerable emotional and social burden for some men, and many are unlikely to seek or receive help. Men, and their support networks, require active encouragement throughout diagnosis, treatment and follow-up to overcome barriers and access additional support, particularly for sexual, emotional and psychosocial issues., (© 2017 John Wiley & Sons Ltd.)

Currently, it is unknown whether treatment outcomes derived from randomized controlled trials (RCTs) of cognitive-behavioural therapy (CBT) for problem gamblers still hold when applied to patients seen in routine practice. Thus, data from an RCT of cognitive therapy versus exposure therapy for problem gambling versus patients of a gambling help service were compared. Assessments of problem gambling severity, psychosocial impairment, and alcohol use were undertaken at baseline and post-treatment and evaluated within a counterfactual framework. Findings showed that the contrast between routine CBT for pokies and horse betting had a significant effect, indicative of a 62% lower gambling urge score if routine CBT recipients had all been horse/track betters opposed to gambling with "pokies." However, the majority of contrasts indicated therapeutic outcomes achieved in routine CBT treatments were of equivalent robustness relative to RCT conditions. The present findings infer routine practice treatment outcomes are as efficacious as those generated in RCT contexts., (Copyright © 2017 John Wiley & Sons, Ltd.)

In response to the five commentaries on our paper 'Comparative approaches to gentrification: lessons from the rural', we open up more 'windows' on rural gentrification and its urban counterpart. First, we highlight the issues of metrocentricity and urbanormativity within gentrification studies, highlighting their employment by our commentators. Second, we consider the issue of displacement and its operation within rural space, as well as gentrification as a coping strategy for neoliberal existence and connections to more-than-human natures. Finally, we consider questions of scale, highlighting the need to avoid naturalistic conceptions of scale and arguing that attention could be paid to the role of material practices, symbolizations and lived experiences in producing scaled geographies of rural and urban gentrification., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The epistemologies and politics of comparative research are prominently debated within urban studies, with 'comparative urbanism' emerging as a contemporary lexicon of urban studies. The study of urban gentrification has, after some delay, come to engage with these debates, which can be seen to pose a major challenge to the very concept of gentrification. To date, similar debates or developments have not unfolded within the study of rural gentrification. This article seeks to address some of the challenges posed to gentrification studies through an examination of strategies of comparison and how they might be employed within a comparative study of rural gentrification. Drawing on Tilly ( Big structures Large Processes Huge Comparisons . New York: Russell Sage), examples of four 'strategies of comparison' are identified within studies of urban and rural gentrification, before the paper explores how 'geographies of the concept' and 'geographies of the phenomenon' of rural gentrification in the United Kingdom, United States and France may be investigated using Latour's ( Pandora's Hope . London: Harvard University Press) notion of 'circulatory sociologies of translation'. The aim of our comparative discussion is to open up dialogues on the challenges of comparative studies that employ conceptions of gentrification and also to promote reflections of the metrocentricity of recent discussions of comparative research., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ectomycorrhizal (ECM) fungi can influence the establishment and performance of host species by increasing nutrient and water absorption. Therefore, understanding the response of ECM fungi to expected changes in the global climate is crucial for predicting potential changes in the composition and productivity of forests. While anthropogenic activity has, and will continue to, cause global temperature increases, few studies have investigated how increases in temperature will affect the community composition of ectomycorrhizal fungi. The effects of global warming are expected to be particularly strong at biome boundaries and in the northern latitudes. In the present study, we analyzed the effects of experimental manipulations of temperature and canopy structure (open vs. closed) on ectomycorrhizal fungi identified from roots of host seedlings through 454 pyrosequencing. The ecotonal boundary site selected for the study was between the southern boreal and temperate forests in northern Minnesota, USA, which is the southern limit range for Picea glauca and Betula papyrifera and the northern one for Pinus strobus and Quercus rubra. Manipulations that increased air and soil temperature by 1.7 and 3.4 °C above ambient temperatures, respectively, did not change ECM richness but did alter the composition of the ECM community in a manner dependent on host and canopy structure. The prediction that colonization of boreal tree species with ECM symbionts characteristic of temperate species would occur was not substantiated. Overall, only a small proportion of the ECM community appears to be strongly sensitive to warming.

Insects and other arthropods transmit devastating human diseases, and these vectors use chemical senses to target humans. Understanding how these animals detect, respond, and adapt to volatile odorants may lead to novel ways to disrupt host localization or mate recognition in these pests. The past decade has led to remarkable progress in understanding odorant detection in arthropods. Insects use odorant-gated ion channels, first discovered in Drosophila melanogaster , to detect volatile chemicals. In flies, 60 "tuning" receptor subunits combine with a common subunit, Orco ( o dorant r eceptor co receptor) to form ligand-gated ion channels. The mechanisms underlying odorant receptor desensitization in insects are largely unknown. Recent work reveals that dephosphorylation of serine 289 on the shared Orco subunit is responsible for slow, odor-induced receptor desensitization. Dephosphorylation has no effect on the localization of the receptor protein, and activation of the olfactory neurons in the absence of odor is sufficient to induce dephosphorylation and desensitization. These findings reveal a major component of receptor modulation in this important group of disease vectors, and implicate a second messenger feedback mechanism in this process., Competing Interests: Declaration Of Conflicting Interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Most studies describing the human gut microbiome in healthy and diseased states have emphasized the bacterial component, but the fungal microbiome (i.e., the mycobiome) is beginning to gain recognition as a fundamental part of our microbiome. To date, human gut mycobiome studies have primarily been disease centric or in small cohorts of healthy individuals. To contribute to existing knowledge of the human mycobiome, we investigated the gut mycobiome of the Human Microbiome Project (HMP) cohort by sequencing the Internal Transcribed Spacer 2 (ITS2) region as well as the 18S rRNA gene., Results: Three hundred seventeen HMP stool samples were analyzed by ITS2 sequencing. Fecal fungal diversity was significantly lower in comparison to bacterial diversity. Yeast dominated the samples, comprising eight of the top 15 most abundant genera. Specifically, fungal communities were characterized by a high prevalence of Saccharomyces, Malassezia, and Candida, with S. cerevisiae, M. restricta, and C. albicans operational taxonomic units (OTUs) present in 96.8, 88.3, and 80.8% of samples, respectively. There was a high degree of inter- and intra-volunteer variability in fungal communities. However, S. cerevisiae, M. restricta, and C. albicans OTUs were found in 92.2, 78.3, and 63.6% of volunteers, respectively, in all samples donated over an approximately 1-year period. Metagenomic and 18S rRNA gene sequencing data agreed with ITS2 results; however, ITS2 sequencing provided greater resolution of the relatively low abundance mycobiome constituents., Conclusions: Compared to bacterial communities, the human gut mycobiome is low in diversity and dominated by yeast including Saccharomyces, Malassezia, and Candida. Both inter- and intra-volunteer variability in the HMP cohort were high, revealing that unlike bacterial communities, an individual's mycobiome is no more similar to itself over time than to another person's. Nonetheless, several fungal species persisted across a majority of samples, evidence that a core gut mycobiome may exist. ITS2 sequencing data provided greater resolution of the mycobiome membership compared to metagenomic and 18S rRNA gene sequencing data, suggesting that it is a more sensitive method for studying the mycobiome of stool samples.

Background: Nonmuscle invasive bladder cancer (NMIBC) is a chronic condition requiring intensive follow-up, repeated endoscopic examinations, tumor resections, and intravesical treatments that can occur every 3 months for life. In this clinical context, patient-reported outcomes (PROs) are a critical concern for patients and their managing clinicians. PROs have enormous potential to be integral to treatment assessment and recommendations for NMIBC; however, current PRO measures are inadequate for NMIBC because they lack key NMIBC-specific symptoms and side effects associated with contemporary treatments., Objective: The overarching aim of this study was to develop and evaluate a patient-reported symptom index (SI) for individuals with NMIBC (the NMIBC-SI) that is acceptable to patients; reliable, valid, and responsive to differences between contemporary treatments for NMIBC; and fit for purpose as an endpoint in clinical trials., Methods: The NMIBC-SI will be evaluated in 2 field tests across a total of 3 years. Field test 1 is a cross-sectional study design involving 225 adult NMIBC patients recruited while undergoing active treatment or those who completed final treatment within the past week. Data collected include patient demographics, clinical features of the tumor, risk category, treatment type, comorbidity, and PROs. Field test 2 is a prospective longitudinal study involving 225 newly diagnosed NMIBC-SI patients. Clinical data and patient-completed questionnaires will be collected at 4 time points during treatment: before tumor resection, 1 week after resection, end-of-induction intravesical therapy, and 1-year follow-up. Standard psychometric tests will be performed to assess the reliability, validity, responsiveness, and clinical utility of the NMIBC-SI., Results: Participant recruitment to field test 1 commenced in February 2017. Recruitment for field test 2 is planned to commence in January 2018. Final results are expected to be published in 2019. The NMIBC-SI will be freely available for use via registration., Conclusions: This study protocol contains detailed methods that will be used across multiple international sites. Phase 2 in the development of the NMIBC-SI will enable a comprehensive evaluation of its reliability, validity, and responsiveness to ensure that the NMIBC-SI is fit for purpose in clinical research and provides an evidence base for the ongoing improvement of future therapies for NMIBC., Trial Registration: ClinicalTrials.gov NCT03091764; http://clinicaltrials.gov/ct2/showNCT03091764 (Archived by WebCite at http://www.webcitation.org/6umBhQeNX)., (©Claudia Rutherford, Madeleine T King, David P Smith, Daniel SJ Costa, Margaret-Ann Tait, Manish I Patel, NMIBC-SI Working Group. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 08.11.2017.)

Background: The simultaneous adoption of laparoscopy and partial nephrectomy (PN) has been reported to result in unintended consequences. We aim to examine the contemporary (2001-2009) trends in use of PN and laparoscopy within a population-wide database., Methods: All renal cell carcinomas diagnosed between 2001 and 2009 in New South Wales, Australia, were identified from the Central Cancer Registry. Records of treatment were electronically linked. All patients with localized renal cell carcinoma who underwent surgical treatment were selected for this study (3771 patients). Follow-up was to the end of 2010. Multivariable logistic regression analysis was used to determine predictors of PN and laparoscopy., Results: In the entire cohort, 150 (4%), 495 (13%), 1516 (40%) and 1610 (43%) received laparoscopic PN, open PN, laparoscopic radical nephrectomy (RN) and open RN, respectively. Between the years 2001 and 2009, there was a gradual increase in the use of PN except between 2005 and 2007. Between 2001 and 2009, a rapid uptake of laparoscopy was observed. Multivariable analysis demonstrated that age (OR: 0.99 (0.98-0.99)), year of surgery (OR: 1.15 (1.11-1.19)), comorbidity (OR: 1.40 (1.12-1.76)) and hospital case load >8/year (OR: 2.39 (1.49-3.81)) predicted use of PN. Year of surgery (OR: 1.19 (1.15-1.21)), comorbidity (OR: 0.70 (0.58-0.85)), non-teaching hospital (OR: 0.70 (0.53-0.93)), private hospital (OR: 1.86 (1.45-2.38)) and hospital case load > 8/year (OR: 3.36 (2.22-5.09)) predicted use of laparoscopy., Conclusion: The unintended decrease in PN associated with increased use of laparoscopic RN had reversed by 2009. Hospital case load predicts the use of PN and laparoscopy., (© 2016 Royal Australasian College of Surgeons.)

The use of cytoreductive nephrectomy (CRN) in the targeted therapy era is still debated. We aimed to determine factors associated with reduced use of CRN and determine the effect of CRN on overall survival in patients with metastatic renal cell carcinoma (RCC). All advanced RCC diagnosed between 2001 and 2009 in New South Wales, Australia, were identified from the Central Cancer Registry. Records of treatment and death were electronically linked. Follow-up was to the end of 2011. Multivariable logistic regression analysis was used to determine factors associated with the receipt of CRN. Cox proportional hazards model was used to determine factors associated with survival. A total of 1062 patients were identified with metastatic RCC of whom 289 (27%) received CRN. There was no difference in the use of CRN over the time period of the study. Females (OR 0.68 (95% CI: 0.48-0.96)), unmarried individuals (OR 0.68 (95% CI: 0.48-0.96)), treatment in a nonteaching hospital (OR 0.26 (95% CI: 0.18-0.36)) and individuals without private insurance (OR 0.29 (95% CI: 0.20-0.41)) all had reduced likelihood of receiving CRN. On multivariable analysis, not receiving CRN resulted in a 90% increase in death (HR 1.90 (95% CI: 1.61-2.25)). In addition, increasing age (P < 0.001), increasing Charlson comorbidity status (P = 0.002) and female gender also had a significant independent association with death. Despite a strong association with improved survival, individuals who are elderly, female, have treatment in a nonteaching facility or have no private insurance have a reduced likelihood of receiving CRN., (© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Context: Fibroblast growth factor 21 (FGF21) secretion has been shown to respond directly to carbohydrate consumption, with glucose, fructose, and sucrose all reported to increase plasma levels of FGF21 in rodents and humans. However, carbohydrate consumption also results in secretion of insulin., Objective: The aim of this study was to examine the combined and independent effects of hyperglycemia and hyperinsulinemia on total and bioactive FGF21 in the postprandial period in humans, and determine whether this effect is attenuated in conditions of altered insulin secretion and action., Methods: Circulating glucose, insulin, total and bioactive FGF21, and fibroblast activation protein were measured in adults with and without type 2 diabetes (T2D) following an oral glucose tolerance test (OGTT), and under a series of insulin and glucose clamp conditions and following high-fat diet in healthy adults., Results: Circulating total and bioactive FGF21 levels responded acutely to OGTT, and their ratio was attenuated in T2D patients with reduced postprandial insulin response. The clamp studies revealed that insulin but not glucose accounts for the postprandial rise in FGF21. Finally, there was an attenuated rise in FGF21 in response to a high-fat dietary intervention that is known to alter insulin-stimulated substrate utilization in metabolically active tissues., Conclusions: Insulin rather than glucose per se increases total and bioactive FGF21 in the postprandial period in adult humans. Understanding the impact of T2D on bioactive FGF21 will have a significant effect upon the efficacy of therapeutic agents designed to target the FGF21 pathway., (Copyright © 2017 Endocrine Society)

Purpose: Non-muscle invasive bladder cancer (NMIBC) is a chronic condition requiring repeated treatment and endoscopic examinations that can be life-long. In this context, health-related quality of life (HRQOL) is important to patients and managing clinicians, and integral to treatment recommendations for NMIBC. The aim of this study was to develop a conceptual framework of patient-reported NMIBC symptoms, treatment side effects, and HRQOL impacts from three sources: (1) literature, (2) patients and (3) treating clinicians., Methods: First, we undertook a scoping literature review for studies reporting patient-reported outcomes associated with NMIBC. Outcomes were extracted and grouped conceptually. Then, we conducted semi-structured interviews with patients with NMIBC and treating clinicians. Patients were asked about symptoms and HRQOL impacts experienced from their NMIBC and treatments. Clinicians were asked about commonly reported outcomes, and outcomes they felt were important to assess clinically. Interviews were audio recorded, transcribed and content analysed., Results: A total of 125 symptom- and functioning-related expressions from 18 studies, 26 patients and 20 clinicians were coded into three themes and 18 sub-themes. Patients commonly reported blood in urine and frequent urination. Clinicians considered BCG sepsis and flu-like symptoms important outcomes to assess during treatment for NMIBC., Conclusion: Our empirically derived conceptual framework identifies patient-reported outcomes that are important to people with NMIBC, provides the basis for the development of a new NMIBC-specific symptom index, and guides the design of a comprehensive PRO assessment plan for clinical practice in NMIBC and future clinical trials of treatments for NMIBC.

The increased prevalence of obesity and its cardiometabolic implications demonstrates the imperative to identify novel therapeutic targets able to effect meaningful metabolic changes in this population. Antibody-mediated targeting of fibroblast growth factor receptor 1c isoform (FGFR1c) has been shown to ameliorate hyperglycemia and protect from diet- and genetically-induced obesity in rodents and nonhuman primates. However, it is currently unknown which tissue(s) contribute to this glucose-lowering effect. Thus, to elucidate this effect, we treated euglycemic mice with H7, a monoclonal antibody that selectively targets FGFR1c, and used whole-body positron emission computed tomography with a glucose tracer (18F-fluorodeoxyglucose). Treatment with H7 increased basal glucose uptake in white adipose tissue (WAT), brown adipose tissue (BAT), the brain, and liver but reduced it in the quadriceps muscles. Consequentially, blood glucose was significantly reduced in response to treatment. Under insulin-stimulated conditions, the effects of H7 were maintained in WAT, BAT, liver, and muscle. Treatment with H7 decreased triglyceride (TG) content and increased adipose TG lipase content in white adipose tissue, while increasing activation of acetyl coenzyme A carboxylase, suggesting futile cycling of TGs, albeit favoring net hydrolysis. We demonstrated, in vitro, this is a direct effect of treatment in adipose tissue, as basal cellular respiration and glucose uptake were increased in response to treatment. Taken together, these data suggest that antibody-mediated targeting of FGFR1c exerts its powerful glucose-lowering efficacy primarily due to increased glucose uptake in adipose tissue., (Copyright © 2017 Endocrine Society.)

Background: Late onset sepsis (LOS) in preterm infants is associated with considerable morbidity and mortality. While studies have implicated gut bacteria in the aetiology of the disease, functional analysis and mechanistic insights are generally lacking. We performed temporal bacterial (n = 613) and metabolomic (n = 63) profiling on extensively sampled stool from 7 infants with LOS and 28 matched healthy (no LOS or NEC) controls., Results: The bacteria isolated in diagnostic blood culture usually corresponded to the dominant bacterial genera in the gut microbiome. Longitudinal changes were monitored based on preterm gut community types (PGCTs), where control infants had an increased number of PGCTs compared to LOS infants (P = 0.011). PGCT 6, characterised by Bifidobacteria dominance, was only present in control infants. Metabolite profiles differed between LOS and control infants at diagnosis and 7 days later, but not 7 days prior to diagnosis. Bifidobacteria was positively correlated with control metabolites, including raffinose, sucrose, and acetic acid., Conclusions: Using multi-omic analysis, we show that the gut microbiome is involved in the pathogenesis of LOS. While the causative agent of LOS varies, it is usually abundant in the gut. Bifidobacteria dominance was associated with control infants, and the presence of this organism may directly protect, or act as a marker for protection, against gut epithelial translocation. While the metabolomic data is preliminary, the findings support that gut development and protection in preterm infants is associated with increased in prebiotic oligosaccharides (e.g. raffinose) and the growth of beneficial bacteria (e.g. Bifidobacterium).

Chronic infection and associated inflammation have long been suspected to promote human carcinogenesis. Recently, certain gut bacteria, including some in the Fusobacterium genus, have been implicated in playing a role in human colorectal cancer development. However, the Fusobacterium species and subspecies involved and their oncogenic mechanisms remain to be determined. We sought to identify the specific Fusobacterium spp. and ssp. in clinical colorectal cancer specimens by targeted sequencing of Fusobacterium 16S ribosomal RNA gene. Five Fusobacterium spp. were identified in clinical colorectal cancer specimens. Additional analyses confirmed that Fusobacterium nucleatum ssp. animalis was the most prevalent F. nucleatum subspecies in human colorectal cancers. We also assessed inflammatory cytokines in colorectal cancer specimens using immunoassays and found that expression of the cytokines IL17A and TNFα was markedly increased but IL21 decreased in the colorectal tumors. Furthermore, the chemokine (C-C motif) ligand 20 was differentially expressed in colorectal tumors at all stages. In in vitro co-culture assays, F. nucleatum ssp. animalis induced CCL20 protein expression in colorectal cancer cells and monocytes. It also stimulated the monocyte/macrophage activation and migration. Our observations suggested that infection with F. nucleatum ssp. animalis in colorectal tissue could induce inflammatory response and promote colorectal cancer development. Further studies are warranted to determine if F. nucleatum ssp. animalis could be a novel target for colorectal cancer prevention and treatment. Cancer Prev Res; 10(7); 398-409. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Parkinson's disease is a multifactorial neurodegenerative disorder, the aetiology of which remains elusive. The primary clinical feature of progressively impaired motor control is caused by a loss of midbrain substantia nigra dopamine neurons that have a high α-synuclein (α-syn) and iron content. α-Syn is a neuronal protein that is highly modified post-translationally and central to the Lewy body neuropathology of the disease. This review provides an overview of findings on the role post translational modifications to α-syn have in membrane binding and intracellular vesicle trafficking. Furthermore, we propose a concept in which acetylation and phosphorylation of α-syn modulate endocytic import of iron and vesicle transport of dopamine during normal physiology. Disregulated phosphorylation and oxidation of α-syn mediate iron and dopamine dependent oxidative stress through impaired cellular location and increase propensity for α-syn aggregation. The proposition highlights a connection between α-syn, iron and dopamine, three pathological components associated with disease progression in sporadic Parkinson's disease.

The short and long-term impact of birth mode on the developing gut microbiome in neonates has potential implications for the health of infants. In term infants, the microbiome immediately following birth across multiple body sites corresponds to birth mode, with increased Bacteroides in vaginally delivered infants. We aimed to determine the impact of birth mode of the preterm gut microbiome over the first 100 days of life and following neonatal intensive care unit (NICU) discharge. In total, 867 stool samples from 46 preterm infants (21 cesarean and 25 vaginal), median gestational age 27 weeks, were sequenced (V4 region 16S rRNA gene, Illumina MiSeq). Of these, 776 samples passed quality filtering and were included in the analysis. The overall longitudinal alpha-diversity and within infant beta-diversity was comparable between cesarean and vaginally delivered infants. Vaginally delivered infants kept significantly more OTUs from 2 months of life and following NICU discharge, but OTUs lost, gained, and regained were not different based on birth mode. Furthermore, the temporal progression of dominant genera was comparable between birth modes and no significant difference was found for any genera following adjustment for covariates. Lastly, preterm gut community types (PGCTs) showed some moderate differences in very early life, but progressed toward a comparable pattern by week 5. No PGCT was significantly associated with cesarean or vaginal birth. Unlike term infants, birth mode was not significantly associated with changes in microbial diversity, composition, specific taxa, or overall microbial development in preterm infants. This may result from the dominating effects of NICU exposures including the universal use of antibiotics immediately following birth and/or the lack of Bacteroides colonizing preterm infants.

Objective: The purpose of this paper is to describe chiropractic management of a patient with neuralgic amyotrophy (NA) and to provide discussion regarding presentation, differential diagnosis, management and prognosis of idiopathic NA., Case Presentation: An 85 year old Caucasian male presented to a chiropractic clinic with right periscapular and lateral rib cage pain. The patient had previously sought evaluation and treatment from multiple health care providers and underwent multiple interventions without relief., Intervention and Outcome: The patient was managed with a course of chiropractic care and an ongoing home exercise program was carried out. The patient reported spontaneous resolution of pain approximately 14 months post onset., Summary: NA is a poorly known clinical entity amongst health care providers and poses challenges in timely and proper diagnosis. Recognition of NA is important for patients to be best managed and for more optimal patient outcomes to be achieved.

Background: Understanding longitudinal variability of the microbiome in ill patients is critical to moving microbiome-based measurements and therapeutics into clinical practice. However, the vast majority of data regarding microbiome stability are derived from healthy subjects. Herein, we sought to determine intra-patient temporal microbiota variability, the factors driving such variability, and its clinical impact in an extensive longitudinal cohort of hospitalized cancer patients during chemotherapy., Methods: The stool (n = 365) and oral (n = 483) samples of 59 patients with acute myeloid leukemia (AML) undergoing induction chemotherapy (IC) were sampled from initiation of chemotherapy until neutrophil recovery. Microbiome characterization was performed via analysis of 16S rRNA gene sequencing. Temporal variability was determined using coefficients of variation (CV) of the Shannon diversity index (SDI) and unweighted and weighted UniFrac distances per patient, per site. Measurements of intra-patient temporal variability and patient stability categories were analyzed for their correlations with genera abundances. Groups of patients were analyzed to determine if patients with adverse outcomes had significantly different levels of microbiome temporal variability. Potential clinical drivers of microbiome temporal instability were determined using multivariable regression analyses., Results: Our cohort evidenced a high degree of intra-patient temporal instability of stool and oral microbial diversity based on SDI CV. We identified statistically significant differences in the relative abundance of multiple taxa amongst individuals with different levels of microbiota temporal stability. Increased intra-patient temporal variability of the oral SDI was correlated with increased risk of infection during IC (P = 0.02), and higher stool SDI CVs were correlated with increased risk of infection 90 days post-IC (P = 0.04). Total days on antibiotics was significantly associated with increased temporal variability of both oral microbial diversity (P = 0.03) and community structure (P = 0.002)., Conclusions: These data quantify the longitudinal variability of the oral and gut microbiota in AML patients, show that increased variability was correlated with adverse clinical outcomes, and offer the possibility of using stabilizing taxa as a method of focused microbiome repletion. Furthermore, these results support the importance of longitudinal microbiome sampling and analyses, rather than one time measurements, in research and future clinical practice.

Objective: To develop a method for estimating the future numbers of prostate cancer survivors requiring different levels of care., Design, Setting and Participants: Analysis of population-based cancer registry data for prostate cancer cases (aged 18-84 years) diagnosed in 1996-2007, and a linked dataset with hospital admission data for men with prostate cancer diagnosed during 2005-2007 in New South Wales (NSW), Australia., Methods: Cancer registry data (1996-2007) were used to project complete prostate cancer prevalence in NSW, Australia for 2008-2017, and treatment information from hospital records (2005-2007) was used to estimate the inpatient care needs during the first year after diagnosis. The projected complete prevalence was divided into care needs-based groups. We first divided the cohort into two groups based on patient's age (<75 and 75-84 years). The younger cohort was further divided into initial care and monitoring phases. Cause of death data were used as a proxy for patients requiring last year of life prostate cancer care. Finally, episode data were used to estimate the future number of cases with metastatic progression., Results: Of the estimated total of 60,910 men with a previous diagnosis of prostate cancer in 2017, the largest groups will be older patients (52.0%) and younger men who require monitoring (42.5%). If current treatment patterns continue, in the first year post-diagnosis 41% (1380) of patients (<75 years) will have a radical prostatectomy, and 52.6% (1752) will be likely to have either active surveillance, external beam radiotherapy or androgen deprivation therapy. About 3% will require care for subsequent metastases, and 1288 men with prostate cancer are likely to die from the disease in 2017., Conclusions: This method extends the application of routinely collected population-based data, and can contribute much to the knowledge of the number of men with prostate cancer and their health care requirements. This could be of significant use in planning future cancer care services and facilities in Australia., Competing Interests: The authors declare that they have no competing interests.

Purpose Advanced prostate cancer (PC) is associated with substantial psychosocial morbidity. We sought to determine whether mindfulness-based cognitive therapy (MBCT) reduces distress in men with advanced PC. Methods Men with advanced PC (proven metastatic and/or castration-resistant biochemical progression) were randomly assigned to an 8-week, group-based MBCT intervention delivered by telephone (n = 94) or to minimally enhanced usual care (n = 95). Primary intervention outcomes were psychological distress, cancer-specific distress, and prostate-specific antigen anxiety. Mindfulness skills were assessed as potential mediators of effect. Participants were assessed at baseline and were followed up at 3, 6, and 9 months. Main statistical analyses were conducted on the basis of intention to treat. Results Fourteen MBCT groups were conducted in the intervention arm. Facilitator adherence ratings were high (> 93%). Using random-effects mixed-regression models, intention-to-treat analyses indicated no significant changes in intervention outcomes or in engagement with mindfulness for men in MBCT compared with those receiving minimally enhanced usual care. Per-protocol analyses also found no differences between arms in outcomes or engagement, with the exception of the mindfulness skill of observing, which increased over time for men in MBCT compared with usual care ( P = .032). Conclusion MBCT in this format was not more effective than minimally enhanced usual care in reducing distress in men with advanced PC. Future intervention research for these men should consider approaches that map more closely to masculinity.

Objectives: To identify reasons for prostate cancer stage being recorded as 'unknown' in Australia's largest population-based cancer registry., Design: Prospective population-based cohort., Setting: New South Wales (NSW) is the most populous state in Australia, with almost one third of the total national population., Participants: NSW Cancer Registry (NSWCR) records for prostate cancer cases diagnosed in 2001-2009 were linked to the NSW Admitted Patient Data Collection (APDC) for 2000-2010. All patients in this study had a minimum of 12 months follow-up in the hospital episode records after their date of diagnosis as recorded by the NSWCR., Main Outcome Measures: Incidence of 'unknown' stage prostate cancer and cancer-specific survival., Results: Of 50 597 prostate cancer cases, 39.9% were recorded as having 'unknown' stage. Up to 4 months after diagnosis, 77.2% of cases without a hospital-reported cancer diagnosis were recorded as having 'unknown' stage. Among those patients with a hospital-reported cancer diagnosis, stage was 'unknown' for 7.6% of cases who received a radical prostatectomy (RP) and for 34.0% of cases who had procedures other than RP. In the latter group, the factors that were related to having 'unknown' stage were living in disadvantaged areas (adjusted OR (aOR) range: 1.13 to 1.20), attending a private hospital (aOR range: 1.25 to 2.13), having day-only admission for care (aOR=1.23, 95% CI 1.11 to 1.36), or having procedures other than multiple procedures with imaging (eg, biopsy only, aOR range: 1.11 to 1.45)., Conclusions: Over half of 'unknown' stage prostate cancer cases did not have a hospital-reported prostate cancer diagnosis within the 4 months after initial diagnosis. We identified differences in the likelihood of cases being recorded as 'unknown' stage based on socioeconomic status and facility type, which suggests that further investigation of reporting practices in relation to diagnostic and treatment pathways is required., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

The corticioid fungi are commonly encountered, highly diverse, ecologically important, and understudied. We collected specimens in 60 pine and spruce forests across North America to survey corticioid fungal frequency and distribution and to compile an internal transcribed spacer (ITS) database for the group. Sanger sequences from the ITS region of vouchered specimens were compared with sequences on GenBank and UNITE, and with high-throughput sequence data from soil and roots taken at the same sites. Out of 425 high-quality Sanger sequences from vouchered specimens, we recovered 223 distinct operational taxonomic units (OTUs), the majority of which could not be assigned to species by matching to the BLAST database. Corticioid fungi were found to be hyperdiverse, as supported by the observations that nearly two-thirds of our OTUs were represented by single collections and species estimator curves showed steep slopes with no plateaus. We estimate that 14.8-24.7% of our voucher-based OTUs are likely to be ectomycorrhizal (EM). Corticioid fungi recovered from the soil formed a different community assemblage, with EM taxa accounting for 40.5-58.6% of OTUs. We compared basidioma sequences with EM root tips from our data, GenBank, or UNITE, and with this approach, we reiterate existing speculations that Trechispora stellulata is EM. We found that corticioid fungi have a significant distance-decay pattern, adding to the literature supporting fungi as having geographically structured communities. This study provides a first view of the diversity of this important group across North American pine forests, but much of the biology and taxonomy of these diverse, important, and widespread fungi remains unknown.

The purpose of this study was to understand the extent, nature and variability of the current economic burden of prostate cancer among Australian men. An online cross-sectional survey was developed that combined pre-existing economic measures and new questions. With few exceptions, the online survey was viable and acceptable to participants. The main outcomes were self-reported out-of-pocket costs of prostate cancer diagnosis and treatment, changes in employment status and household finances. Men were recruited from prostate cancer support groups throughout Australia. Descriptive statistical analyses were undertaken. A total of 289 men responded to the survey during April and June 2013. Our study found that men recently diagnosed (within 16 months of the survey) (n = 65) reported spending a median AU$8000 (interquartile range AU$14 000) for their cancer treatment while 75% of men spent up to AU$17 000 (2012). Twenty per cent of all men found the cost of treating their prostate cancer caused them 'a great deal' of distress. The findings suggest a large variability in medical costs for prostate cancer treatment with 5% of men spending $250 or less in out-of-pocket expenses and some men facing very high costs. On average, respondents in paid employment at diagnosis stated that they had retired 4-5 years earlier than planned., (© 2015 The Authors. European Journal of Cancer Care Published by John Wiley & Sons Ltd.)

Background: The preterm microbiome is crucial to gut health and may contribute to necrotising enterocolitis (NEC), which represents the most significant pathology affecting preterm infants. From a cohort of 318 infants, <32 weeks gestation, we selected 7 infants who developed NEC (defined rigorously) and 28 matched controls. We performed detailed temporal bacterial (n = 641) and metabolomic (n = 75) profiling of the gut microbiome throughout the disease., Results: A core community of Klebsiella, Escherichia, Staphyloccocus, and Enterococcus was present in all samples. Gut microbiota profiles grouped into six distinct clusters, termed preterm gut community types (PGCTs). Each PGCT reflected dominance by the core operational taxonomic units (OTUs), except of PGCT 6, which had high diversity and was dominant in bifidobacteria. While PGCTs 1-5 were present in infants prior to NEC diagnosis, PGCT 6 was comprised exclusively of healthy samples. NEC infants had significantly more PGCT transitions prior to diagnosis. Metabolomic profiling identified significant pathways associated with NEC onset, with metabolites involved in linoleate metabolism significantly associated with NEC diagnosis. Notably, metabolites associated with NEC were the lowest in PGCT 6., Conclusions: This is the first study to integrate sequence and metabolomic stool analysis in preterm neonates, demonstrating that NEC does not have a uniform microbial signature. However, a diverse gut microbiome with a high abundance of bifidobacteria may protect preterm infants from disease. These results may inform biomarker development and improve understanding of gut-mediated mechanisms of NEC.

Objective: To examine the extent to which mindfulness skills influence psychological distress and health-related quality of life (HRQOL) in men with metastatic or castration-resistant biochemical progression of prostate cancer., Patients and Methods: A cross-sectional survey of 190 men (46 % response; mean age 71 years, SD = 8.7, range 40-91 years) with advanced prostate cancer, assessed psychological and cancer-specific distress, HRQOL. Mindfulness skills were assessed as potential predictors of adjustment outcomes., Results: Overall, 39 % of men reported high psychological distress. One third had accessed psychological support previously although only 10 % were under current psychological care. One quarter had accessed a prostate cancer support group in the past six months. Higher HRQOL and lower cancer-specific and global psychological distress were related to non-judging of inner experience (p < 0.001). Higher HRQOL and lower psychological distress were related to acting with awareness (p < 0.001). Lower distress was also related to higher non-reactivity to inner experience and a lower level of observing (p < 0.05)., Conclusions: Men with advanced prostate cancer are at risk of poor psychological outcomes. Psychological flexibility may be a promising target for interventions to improve adjustment outcomes in this patient group., Clinical Trial Registry: Trial Registration: ACTRN12612000306819., Competing Interests: All authors had no conflict of interest, including relevant financial interests, activities, relationships, and affiliations to declare relating to this manuscript.

Insects have evolved sophisticated olfactory reception systems to sense exogenous chemical signals. Odorant receptors (ORs) on the membrane of chemosensory neurons are believed to be key molecules in sensing exogenous chemical cues. ORs in different species of insects are diverse and should tune a species to its own specific semiochemicals relevant to their survival. The orthopteran insect, locust (Locusta migratoria), is a model hemimetabolous insect. There is very limited knowledge on the functions of locust ORs although many locust OR genes have been identified in genomic sequencing experiments. In this paper, a locust OR, LmigOR3 was localized to neurons housed in trichoid sensilla by in situ hybridization. LmigOR3 was expressed as a transgene in Drosophila trichoid olfactory neurons (aT1) lacking the endogenous receptor Or67d and the olfactory tuning curve and dose-response curves were established for this locust receptor. The results show that LmigOR3 sensitizes neurons to ketones, esters and heterocyclic compounds, indicating that LmigOR3 is a broadly tuned receptor. LmigOR3 is the first odorant receptor from Orthoptera that has been functionally analyzed in the Drosophila aT1 system. This work demonstrates the utility of the Drosophila aT1 system for functional analysis of locust odorant receptors and suggests that LmigOR3 may be involved in detecting food odorants, or perhaps locust body volatiles that may help us to develop new control methods for locusts., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Childhood bone cancer though rare, has very limited treatment choices, with poor survival rates and often involving amputation. We developed a novel molecule, 2', 4'-dihydroxy-dithion-dibenzoyl-methane and tested it on hepatic, colon, lung and osteoblast cancer cell lines. Thionylation of 2', 4'- dihydroxydibenzoylmethane led to selective targeting of bone cancer cells, stopping their growth and leading to their death without affecting non-cancerous cells within the bone marrow or other non-malignant cells., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objectives: To study the patterns of care of penile cancer diagnosed in the state of New South Wales (NSW) over a 10 year period and determine factors that are associated with differences in survival., Patients and Methods: All invasive penile cancer diagnosed between 2001 and 2009 in NSW, Australia, were identified from the Central Cancer Registry. Records of treatment from the Admitted Patient Data Collection and deaths from the Registry of Births Deaths and Marriages were electronically linked. Predictors of receiving an inguinal lymph node dissection (ILND) were analysed using multivariable logistic regression. Survival analyses were performed with Kaplan-Meier and Cox proportional hazards models., Results: A total of 220 men were diagnosed with penile cancer over the 10 years from 69 centres. The median number of penile operations performed over 10 years was <4. Radical penile surgery (partial or total penectomy) was performed in 70% of the cases and the proportion of patients receiving radical surgery increased over time (P = 0.015). Only 53/220 men with invasive penile cancer received an ILND. Younger age and higher stage were the only factors that predicted whether ILND was performed. Overall survival (OS) was predicted by age, stage, marital status and co-morbidity status. Low centre volume decreased OS by 37% (HR 0.63 [95% CI: 0.40-0.97]). For men who received ILND, low centre volume decreased OS by 60% (HR 0.40 [95% CI: 0.19-0.85])., Conclusions: There is a decreasing trend for the use of conservative penile surgery and median centre volumes for penile cancer surgery in NSW are low. A decrease in overall survival is observed in men treated in lower volume surgery centres., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

Background: Despite ever more powerful antibiotics, newer surgical techniques, and enhanced recovery programs, anastomotic leaks remain a clear and present danger to patients. Previous work from our laboratory suggests that anastomotic leakage may be caused by Enterococcus faecalis strains that express a high collagenase phenotype (i.e., collagenolytic). Yet the mechanisms by which the practice of surgery shifts or selects for collagenolytic phenotypes to colonize anastomotic tissues remain unknown., Methods: Here, we hypothesized that morphine, an analgesic agent universally used in gastrointestinal surgery, promotes tissue colonization with collagenolytic E. faecalis and causes anastomotic leak. To test this, rats were administered morphine in a chronic release form as would occur during routine surgery or vehicle. Rats were observed for 6 days and then underwent exploratory laparotomy for anastomotic inspection and tissue harvest for microbial analysis. These results provide further rationale to enhanced recovery after surgery (i.e., ERAS) programs that suggest limiting or avoiding the use of opioids in gastrointestinal surgery., Results: Results demonstrated that compared to placebo-treated rats, morphine-treated rats demonstrated markedly impaired anastomotic healing and gross leaks that correlated with the presence of high collagenase-producing E. faecalis adherent to anastomotic tissues. To determine the direct role of morphine on this response, various isolates of E. faecalis from the rats were exposed to morphine and their collagenase activity and adherence capacity determined in vitro. Morphine increased both the adhesiveness and collagenase production of four strains of E. faecalis harvested from anastomotic tissues, two that were low collagenase producers at baseline, and two that were high collagenase producers at baseline., Conclusion: These results provide further rationale to enhanced recovery after surgery (i.e., ERAS) programs that suggest limiting or avoiding the use of opioids in gastrointestinal surgery.

The Parkinson's disease-associated protein α-synuclein exhibits significant conformational heterogeneity. Bacterially expressed α-synuclein is known to bind to copper, resulting in the formation of aggregation-prone compact conformations. However, in vivo, α-synuclein undergoes acetylation at its N-terminus. Here the effect of this modification and the pathological H50Q mutation on copper binding and subsequent conformational transitions were investigated by electrospray ionization-ion mobility spectrometry-mass spectrometry. We demonstrate that acetylation perturbs the ability of α-synuclein to bind copper and that the H50Q missense mutation in the presence of N-terminal acetylation prevents copper binding. These modifications and mutations prevent the formation of the most compact conformations and inhibit copper-induced aggregation.

Background: Despite increasing data on the impact of the microbiome on cancer, the dynamics and role of the microbiome in infection during therapy for acute myelogenous leukemia (AML) are unknown. Therefore, the authors sought to determine correlations between microbiome composition and infectious outcomes in patients with AML who were receiving induction chemotherapy (IC)., Methods: Buccal and fecal specimens (478 samples) were collected twice weekly from 34 patients with AML who were undergoing IC. Oral and stool microbiomes were characterized by 16S ribosomal RNA V4 sequencing using an Illumina MiSeq system. Microbial diversity and genera composition were associated with clinical outcomes., Results: Baseline stool α-diversity was significantly lower in patients who developed infections during IC compared with those who did not (P = .047). Significant decreases in both oral and stool microbial α-diversity were observed over the course of IC, with a linear correlation between α-diversity change at the 2 sites (P = .02). Loss of both oral and stool α-diversity was associated significantly with the receipt of a carbapenem P < 0.001. Domination events by the majority of genera were transient (median duration, 1 sample), whereas the number of domination events by pathogenic genera increased significantly over the course of IC (P = .002). Moreover, patients who lost microbial diversity over the course of IC were significantly more likely to contract a microbiologically documented infection within the 90 days after IC neutrophil recovery (P = .04)., Conclusions: The current data present the largest longitudinal analyses to date of oral and stool microbiomes in patients with AML and suggest that microbiome measurements could assist with the mitigation of infectious complications of AML therapy. Cancer 2016;122:2186-96. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

The alphaproteobacterium " Candidatus Pelagibacter ubique" strain HTCC1062 and most other members of the SAR11 clade lack genes for assimilatory sulfate reduction, making them dependent on organosulfur compounds that occur naturally in seawater. To investigate how these cells adapt to sulfur limitation, batch cultures were grown in defined medium containing either limiting or nonlimiting amounts of dimethylsulfoniopropionate (DMSP) as the sole sulfur source. Protein and mRNA expression were measured before, during, and after the transition from exponential growth to stationary phase. Two distinct responses were observed, one as DMSP became exhausted and another as the cells acclimated to a sulfur-limited environment. The first response was characterized by increased transcription and translation of all " Ca . Pelagibacter ubique" genes downstream from the previously confirmed S -adenosyl methionine (SAM) riboswitches bhmT , mmuM , and metY . The proteins encoded by these genes were up to 33 times more abundant as DMSP became limiting. Their predicted function is to shunt all available sulfur to methionine. The secondary response, observed during sulfur-limited stationary phase, was a 6- to 10-fold increase in the transcription of the heme c shuttle-encoding gene ccmC and two small genes of unknown function ( SAR11&#95;1163 and SAR11&#95;1164 ). This bacterium's strategy for coping with sulfur stress appears to be intracellular redistribution to support methionine biosynthesis rather than increasing organosulfur import. Many of the genes and SAM riboswitches involved in this response are located in a hypervariable genome region (HVR). One of these HVR genes, ordL , is located downstream from a conserved motif that evidence suggests is a novel riboswitch. IMPORTANCE " Ca . Pelagibacter ubique" is a key driver of marine biogeochemistry cycles and a model for understanding how minimal genomes evolved in free-living anucleate organisms. This study explores the unusual sulfur acquisition strategy that has evolved in these cells, which lack assimilatory sulfate reduction and instead rely on reduced sulfur compounds found in oxic marine environments to meet their cellular quotas. Our findings demonstrate that the sulfur acquisition systems are constitutively expressed but the enzymatic steps leading to the essential sulfur-containing amino acid methionine are regulated by a unique array of riboswitches and genes, many of which are encoded in a rapidly evolving genome region. These findings support mounting evidence that streamlined cells have evolved regulatory mechanisms that minimize transcriptional switching and, unexpectedly, localize essential sulfur acquisition genes in a genome region normally associated with adaption to environmental variation.