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Background Many persons with dementia transition to nursing home care, but little is known about the impact, positive and negative, that this may have on the social isolation and loneliness of their spouse. Methods Using our existing theoretical synthesis of loneliness to provide sensitising concepts, we conducted a deductive grounded theory study of loneliness during the nursing home transitions. We recruited 11 spousal participants to engage in semi-structured remote interviews during 2021. Results Participants provided their own definitions of loneliness, and spoke about their life history of loneliness, the loneliness associated with living with a spouse with dementia, and the loneliness, and alleviation of loneliness through re-engagement with social contacts, associated with their spouse moving to the nursing home. Participants agreed with the idea that loneliness has a physical feeling. More distal parts of the theoretical synthesis, such as the influence that culture and gender have on loneliness, were not corroborated by the findings. Conclusion We conclude that loneliness is a frequent experience among spousal caregivers whose spouse has moved to nursing home care, but that loneliness is also associated with living with a spouse with dementia. Loneliness in this population was aggravated by the COVID-19 pandemic and associated lockdowns. Further research steps will involve more targeted interviewing to focus on the link between transitions and loneliness in this and in other populations.

Selective dorsal rhizotomy (SDR) has been shown to improve gait in the short-term in children with cerebral palsy (CP). Further study is needed to look at the trajectory of outcomes over the longer-term.What are the medium-term effects of SDR on gait compared to a matched CP non-SDR group?Participants underwent SDR at mean age 6.3 years and completed baseline, 1-year and 5-year follow-up gait analyses. Non-SDR participants were matched at baseline. Differences were assessed within and between groups. Kinematic variables were analysed using Statistical non-Parametric Mapping (SnPM). Other gait and clinical data were analysed using Friedman's one-way repeated measure analysis of variance and a Mann-Whitney U-test.The initial SDR group consisted of 29 participants, reducing to 22 at 5-year follow-up. Of these, 15 (68 %) had orthopaedic surgeries either concurrent with or in the intervening period since the SDR, mean 3.3 procedures per participant. The initial non- SDR group had 18 participants, reducing to 17 at 5-year follow-up. Of these, 13 (76 %) had orthopaedic surgeries, mean 5.7 procedures. At 1-year follow-up the SDR group had significantly improved knee extension, ankle dorsiflexion, foot progression, Gait Deviation Index, and normalised step length compared to baseline, p 0.05, and outcomes were maintained at 5-years. At 1-year follow-up the non-SDR group kinematic patterns were unchanged, but at 5-year follow-up this group demonstrated significantly improved knee extension, ankle dorsiflexion and foot progression. There were no significant kinematic differences between the SDR and the non-SDR group at medium-term follow-up.We have documented the trajectory of gait outcomes post-SDR over 3 assessments and found that short-term gait changes endured in the medium-term. However, kinematic changes were similar to a non-SDR group undergoing routine and orthopaedic care. These outcomes are important to guide surgical decision making and to manage treatment goals and expectations.

Background Achieving recruitment targets is a challenge to every clinical trial’s success. Evidence suggests that the recruiter has an impact on a patient's decision to participate in a clinical trial but there is no evidence that it improves recruitment rates. The aim of this study was to determine if the person who recruits the participants to the trial impacts recruitment timelines and targets. We chose ovarian cancer clinical trials to test this. A secondary outcome was to identify if trialists published their recruitment strategies. Methods We identified a body of ovarian cancer (OC) clinical trials between 2010 and 2021. Searches were conducted in CINAHL, PubMed, Medline (OVID and EBSCO) and separately in the New England Journal of Medicine, American Cancer Society Journals, Lancet Oncology, Journal of Clinical Oncology and BMC Cancer. We also identified all associated protocols or supplementary material associated with each trial. We reviewed 139 papers, 30 protocols, 105 registry entries and 26 trial websites associated with 88 phase III OC trials. Results Of the 88 trials, only 31% (n=28) made reference to the recruiter but this was reported only in the protocol so we have no evidence these named recruiters performed the task. Seventy-nine trials were registered on a clinical trial registry, but only 11 (14%) of these included a protocol. None of the trials reviewed published a recruitment strategy or made reference to an available recruitment strategy for the trial. None of the trials reviewed which closed early, or extended recruitment timelines due to slow accrual, reported measures taken to improve recruitment rates before stoppages or changes took place. There were disparities in the reported target recruitment numbers between the protocol, the publication and the registry. Conclusions Trialists need to think carefully about the trial data they collect, the reasons for collection and who the data collection is for. They also need to increase the transparency of their practices. We believe the inclusion of a patient or member of the public at the design phase of the trial would assist this focus.

Received 12th May 2021. Accepted 17th May 2021. Published online 28th May 2021. Issue published 1st August 2021.

Background Children and young people (CYP) are increasingly attending acute paediatric services due to mental health difficulties. 50% of all mental health problems are established by 14 years of age and 75% by 24 years. Underinvestment in mental health has been a longstanding concern, amplified by the COVID-19 pandemic through extra stress caused by prolonged school closures, social isolation and a lack of access to usual support services. In 2020, the Royal College of Paediatrics and Child Health highlighted that suicide is now the leading cause of death in England and Wales for children aged 5-19 years, emphasising the need to prioritise and improve mental health. Paediatricians must develop the knowledge and skills to identify, support and make appropriate referrals for common mental health problems. HEEADSSS is a well-known psychosocial screening tool with eight domains, used to identify potential or actual harm. Objectives Establish whether CYP within the West Midlands, UK are receiving adequate psychosocial assessments on hospital admission and whether healthcare professionals are signposting to relevant services. The primary outcome was the percentage of CYP with documented evidence of being offered a HEEADSSS assessment. Methods A regional prospective audit across nine hospitals was performed for three days per week from 4st -31st January 2021. A standardised proforma was used to gather information from medical records of all CYP aged >12 years admitted to paediatric wards. Pooled data were analysed using Microsoft Excel. Results 231 patients were included. The median age was 14 years old (range 12-17 years). 163(71%) were female. 202 (87%) had no known communication difficulties. 53(23%) were known to CAMHS and 43(19%) to social care. 78/231 (34%) were admitted with mental health as the presenting complaint. 35/231(15%) were documented to be given the opportunity to be spoken to alone;29(82%) accepted. No department had a psychosocial screening tool embedded in the admission document. 158/231(69%) had less than half of the eight domains completed. The median was 1.5 (range 0-8). Home and education/ employment were most frequently asked (37-42%). Eating/exercise, drugs, safety, sexual activity and other activities were the least frequently asked (14-27%). The proportion of those with a concern identified when asked ranged from 18%-39%. However, in self-harm, depression and suicide, only 85/231 (37%) were asked, with concern identified in 87%. 78 patients were admitted for mental health;28(39%) had less than half the domains completed (median 5, range 0-8). Drug use 46/78(59%), safety and sexual activity (both 38/78 (49%)) were inconsistently documented in this group, with concerns identified in 20-26% of those asked. 90/231(39%) were referred to CAMHS, social care, counselling, online or other support services. 16/77(21%) patients with a concern documented in at least one domain were not referred onwards. Conclusions This study demonstrates poor implementation of the HEEADSSS tool on admission, across a wide geographical area. Increased utilisation of a psychosocial screening tool would provide more opportunities to CYP to discuss their psychosocial health and receive appropriate support, in line with national guidance standards. Further work is underway addressing barriers to using HEEADSSS, considering electronic or embedded tools and signposting to relevant services.

The recent publication of a new framework for practice from the British Association of Perinatal Medicine has altered the management of babies born in the UK at the threshold of viability. A risk stratification is used to determine which infants will receive active management, and which receive palliative management. This is achieved through a combination of assessment of risk factors and discussion with parents. The most notable feature of the new framework is the recommendation to consider babies of 22 weeks gestation for active care. This has been the subject of much discussion amongst neonatal and obstetric teams. The framework also emphasises the importance of early transfer to a maternity unit with a co-located neonatal intensive care unit if active management is pursued. This new guidance has led to a change in the way the management of extreme prematurity is approached, and will continue to impact on neonatal, obstetric, and anaesthetic care.

The inaccessibility of living bone marrow (BM) hampers the study of its pathophysiology under myelotoxic stress induced by drugs, radiation or genetic mutations. Here, we show that a vascularized human BM-on-a-chip (BM chip) supports the differentiation and maturation of multiple blood cell lineages over 4 weeks while improving CD34+ cell maintenance, and that it recapitulates aspects of BM injury, including myeloerythroid toxicity after clinically relevant exposures to chemotherapeutic drugs and ionizing radiation, as well as BM recovery after drug-induced myelosuppression. The chip comprises a fluidic channel filled with a fibrin gel in which CD34+ cells and BM-derived stromal cells are co-cultured, a parallel channel lined by human vascular endothelium and perfused with culture medium, and a porous membrane separating the two channels. We also show that BM chips containing cells from patients with the rare genetic disorder Shwachman–Diamond syndrome reproduced key haematopoietic defects and led to the discovery of a neutrophil maturation abnormality. As an in vitro model of haematopoietic dysfunction, the BM chip may serve as a human-specific alternative to animal testing for the study of BM pathophysiology. A vascularized human bone-marrow-on-a-chip improves the maintenance of patient-derived CD34+ cells, and recapitulates clinically relevant aspects of bone marrow injury as well as key haematopoietic defects of patients with a rare genetic disorder.

Background Increased numbers of blood and sputum eosinophils are associated with higher exacerbation frequency and increased asthma severity. In clinical trials, targeting Interleukin-5 has been shown to be a useful therapeutic strategy for patients with severe eosinophilic asthma. Methods Twenty-six patients have been commenced on Reslizumab in our institution since early 2017. Safety and clinical efficacy parameters were recorded at regular intervals. Results Mean ACQ-6 score at the start of treatment was 3.5. The average number of exacerbations in the year preceding treatment was 8.3 per person. 30% of patients had been admitted to hospital at least once over the 12 months preceding therapy. 54% of our patients were on long term oral steroid. Our data showed sustained improvement of Asthma control (Mean improvement in ACQ-6 was 1.7 at 1 year, and 2.0 at 2 years, P = 0.0001). Of the patients who were on long term systemic steroids, 35.7% discontinued steroids completely, with a mean reduction of prednisolone dose of 5.2 mg at 1 year. There was a 79% reduction in the annual exacerbation frequency at 1 year, and 88% at 2 years (P = Conclusions Overall, Reslizumab was well tolerated with discontinuation of treatment due to side effects recorded in only one patient. Our data confirm the utility of anti-IL5 therapy in a carefully selected phenotype of severe asthma with evidence of eosinophilic airway inflammation.

In this paper we disrupt established methodological boundaries in consumer research. We embark on a creative exploration to address the lack of an appropriate methodological toolkit. Graphic narrat...

Play theory has been underutilized to understand consumer behaviour. In this article, we adopt a play theory perspective to understand how consumers respond to and navigate macrostructural influences. The marketplace culture stream of consumer culture theory (CCT) research is particularly well suited to macrostructural analysis from a play theory perspective. We develop an analytical framework derived from play theory to interpret the context of marketplace culture. We show how the types of play foundational to marketplace culture experiences act as expressions of order or disorder to wider macrostructural influences. In contrast to agentic perspectives, we show how marketplace culture experiences, despite their fun appearance, embody the underlying tensions of the intensifying rationality, regulation and competition structuring neoliberal society. Finally, we express concern over the marketer’s control of playground expression and suggest CCT adopt a more critical stance to the commercialization of play.

The actin cytoskeleton plays a central role in platelet formation and function. Alpha-actinins (actinins) are actin filament crosslinking proteins that are prominently expressed in platelets and have been studied in relation to their role in platelet activation since the 1970s. However, within the past decade, several groups have described mutations in ACTN1/actinin-1 that cause congenital macrothrombocytopenia (CMTP)—accounting for approximately 5% of all cases of this condition. These findings are suggestive of potentially novel functions for actinins in platelet formation from megakaryocytes in the bone marrow and/or platelet maturation in circulation. Here, we review some recent insights into the well-known functions of actinins in platelet activation before considering possible roles for actinins in platelet formation that could explain their association with CMTP. We describe what is known about the consequences of CMTP-linked mutations on actinin-1 function at a molecular and cellular level and speculate how these changes might lead to the alterations in platelet count and morphology observed in CMTP patients. Finally, we outline some unanswered questions in this area and how they might be addressed in future studies.

Objectives: Globally, increasing life expectancy has escalated demands on psychiatric services caring for a later life population. It is recognised that those with enduring mental illness may have specific needs with advancing age. In this study, we describe the characteristics of a population aged over 60 years attending a general adult community psychiatric service and compare demographic and clinical features across age and diagnostic categories. The study aims to gather preliminary information which may guide future local mental health service planning. Methods: We conducted a cross-sectional observational study using retrospective chart review of all patients aged over 60 years attending four community mental health teams in North Dublin. Cohorts of attenders were stratified by age comparing 60–64 year age group with the population aged 65 years and over. Attenders were also stratified by diagnosis and regression analysis was used to determine predictors of psychotic disorder diagnosis. Results: The study included 127 patients. There was a higher prevalence of psychotic disorders among those aged 65 years and over (n = 73), while those aged 60–64 years (n = 54) were more likely to have depression and non-affective, non-psychotic disorders. Among the population aged 65 years and over 78% (n = 57) were long-term psychiatric service attenders. Conclusions: The majority of the sample aged 65 years and over were long-term service attenders with a diagnosis of severe mental illness. Further research is warranted to determine optimal service delivery for later life psychiatric service attenders.

Background While prospectively assessed crouch gait in cerebral palsy (CP) does not necessarily progress, prospective changes in clinical examination measures have not been reported. This study prospectively examined the association between selected clinical examination variables and change in crouch gait in a cohort with bilateral CP. Methods Inclusion criteria were a diagnosis of ambulant bilateral CP, knee flexion at mid-stance >190 and a minimum of two-years between gait analyses. The change in kinematic variables was assessed using Statistical Parameter Mapping (SPM) and changes in clinical measures using appropriate paired tests. Linear regression examined the association between progression of crouch and clinical examination variables. Results There was no mean change in crouch in 27 participants over 3.29 years. However, there was significant variability within this group. Clinical hamstring tightness (60.000 to 70.480, p Conclusions The variability crouch gait progression highlights the pitfall of group mean values in such a heterogeneous population. The lack of association between changes in clinical examination variables and changes in crouch highlights the multi-factorial aetiology of this gait pattern and the need for larger prospective studies.

Thrombotic events are common in patients with multiple myeloma (MM), smouldering myeloma (SM) and monoclonal gammopathy of undetermined significance (MGUS). Previous studies have indicated platelet hyperactivation as a feature of thrombotic risk in MM, but there is a dearth of data in MGUS. In the present study, multiparameter analysis of platelet activation and responsiveness was investigated by flow cytometry in patients with MGUS, SM/MM and healthy controls (HCs). The median platelet surface CD63 levels, annexin V and PAC-1 antibody (specific for activated integrin αIIbβ3) binding were significantly elevated in patients with MGUS versus the HCs. These markers were also elevated in SM/MM, but not significantly. In all, 74% of MGUS and 38% of SM/MM patients had one or more elevated marker of platelet activation, compared to 19% of the HCs. Marker-specific hyporesponsiveness of platelets to agonist [adenosine diphosphate (ADP), thrombin receptor-activating peptide 6] stimulation in vitro was observed, with significantly reduced surface levels of P-selectin in response to ADP in patients with MGUS. Platelet-leucocyte aggregates were not altered in patients, while platelet-associated immunoglobulins were elevated in a subset of patients. Overall, we found that platelet hyperactivation is prevalent in both MGUS and SM/MM patients and is potentially related to hyporesponsiveness. These observations suggest that further investigation of the predictive and prognostic value of platelet hyperactivation in such patients is warranted.

Chemotherapy-induced cytopenias are a prevalent and significant issue that worsens clinical outcomes and hinders the effective treatment of cancer. While they are classically associated with traditional cytotoxic chemotherapies, they also occur with newer targeted small molecule drugs and the factors that determine the hematotoxicity profiles of chemotherapies are not fully understood. Here, we explore why Aurora kinase inhibitor drugs cause preferential neutropenia when compared to the cytopenic profiles of targeted small molecule cancer drugs that are FDA approved. By studying drug responses of healthy human hematopoietic cells in vitro and analyzing existing published clinical datasets, we provide evidence that the enhanced vulnerability of neutrophil-lineage cells to Aurora kinase inhibitors is acquired at an early stage of differentiation and is caused by developmental changes in the expression pattern of ATP-binding cassette (ABC) transporters. These data show that hematopoietic cell-intrinsic expression of ABC transporters may be an important factor that determines how some chemotherapies affect the bone marrow. Disclosures David: AstraZeneca: Current Employment. Randle: AstraZeneca: Current Employment. Polanska: AstraZeneca: Current Employment. Urosevic: AstraZeneca: Current Employment. Travers: AstraZeneca: Ended employment in the past 24 months. Ingber: Emulate: Membership on an entity's Board of Directors or advisory committees; BOA Biomedical: Membership on an entity's Board of Directors or advisory committees; Freeflow Medical Devices Inc: Membership on an entity's Board of Directors or advisory committees.

Emerging from the growth of consumer fandom, global football brands have become some of the most profitable in the world, while the football industry can be categorized as big business. Thus, market-orientated practices such as branding, have become synonymous with the spectacle of sporting events. However, the prominence of capitalist ideology within the marketplace has diminished the liberties of extreme football fans, resulting in marketplace exclusion. Extreme fans no longer see their football clubs as symbolic representations of the local community or local culture, but as an embodiment of a globalized, cosmopolitan, market-driven world, detached from the people it originally represented. Digitized communities, including those communities that transcend online environments, have been a topic of great debate among marketing academics, with recent studies advancing the understanding of a number of research contexts, such as; gaming communities, therapeutic communities, and educational communities. Knowledge surrounding the conceptualizations of consumption communities has also advanced, with new modes of online consumer participation emerging within academic literature, such a brand publics. However, despite such advancements, Moufahim et al. (2018) state that critical conversations must continue, specifically pertaining to the darker side of online communities and interaction, which exert forms of social control, exclusion, destruction, and hostility. This netnographic study focuses on how extreme football fans engage in collaborative glocalization, with implications for the manifestation of fan resistant practices which are proliferated and celebrated through the utilization of digital sharing platforms. Extreme fans are no longer engaging in reflexive social performance solely based upon their own experiences, but also the experiences of similar ‘others’. Thus, the current study shows how extreme fan cultures engage in various forms of collaborative glocalization as they seek to align their own identities with that of the broader fan culture ideology. The prevalence of digitized technologies within this resistant fan culture, results in an amplification of deviant acts which permeate transnational boundaries. Such enhances the understanding of how the darker aspects of fan communities manifest through online platforms, and the impact of same.

Actinin-1 mutations cause dominantly inherited congenital macrothrombocytopenia (CMTP), with mutations in the actin-binding domain increasing actinin's affinity for F-actin. In this study, we examined nine CMTP-causing mutations in the calmodulin-like and rod domains of actinin-1. These mutations increase, to varying degrees, actinin's ability to bundle actin filaments in vitro. Mutations within the calmodulin-like domain decrease its thermal stability slightly but do not dramatically affect calcium binding, with mutant proteins retaining calcium-dependent regulation of filament bundling in vitro. The G764S and E769K mutations increase cytoskeletal association of actinin in cells, and all mutant proteins colocalize with F-actin in cultured HeLa cells. Thus, CMTP-causing actinin-1 mutations outside the actin-binding domain also increase actin association, suggesting a common molecular mechanism underlying actinin-1 related CMTP.

ObjectivesThe psychological impact of the COVID-19 pandemic on doctors is a significant concern. Due to the emergence of multiple pandemic waves, longitudinal data on the impact of COVID-19 are vital to ensure an adequate psychological care response. The primary aim was to assess the prevalence and degree of psychological distress and trauma in frontline doctors during the acceleration, peak and deceleration of the COVID-19 first wave. Personal and professional factors associated with psychological distress are also reported.DesignA prospective online three-part longitudinal survey.SettingAcute hospitals in the UK and Ireland.ParticipantsFrontline doctors working in emergency medicine, anaesthetics and intensive care medicine during the first wave of the COVID-19 pandemic in March 2020.Primary outcome measuresPsychological distress and trauma measured using the General Health Questionnaire-12 and the Impact of Events-Revised.ResultsThe initial acceleration survey distributed across networks generated a sample of 5440 doctors. Peak and deceleration response rates from the original sample were 71.6% (n=3896) and 56.6% (n=3079), respectively. Prevalence of psychological distress was 44.7% (n=1334) during the acceleration, 36.9% (n=1098) at peak and 31.5% (n=918) at the deceleration phase. The prevalence of trauma was 23.7% (n=647) at peak and 17.7% (n=484) at deceleration. The prevalence of probable post-traumatic stress disorder was 12.6% (n=343) at peak and 10.1% (n=276) at deceleration. Worry of family infection due to clinical work was the factor most strongly associated with both distress (R2=0.06) and trauma (R2=0.10).ConclusionFindings reflect a pattern of elevated distress at acceleration and peak, with some natural recovery. It is essential that policymakers seek to prevent future adverse effects through (a) provision of vital equipment to mitigate physical and psychological harm, (b) increased awareness and recognition of signs of psychological distress and (c) the development of clear pathways to effective psychological care.Trial registration numberISRCTN10666798.

This ethnography outlines experiences of the marketer-facilitated World Series of Beer Pong. Consumers, in carnival spirit, augment marketer-facilitated mimetic (moderate, controlled) forms of experience with non-mimetic (dangerous, uncontrolled) consumption rituals, enacted in pursuit of contemporary excitement. Consumers serendipitously hijack the facilitating brand’s ideology resulting in the promotion of marketplace tensions. This study contributes to marketing and consumer culture theory by extending current experiential marketing frameworks via the introduction of the branded carnival, a non-mimetic communal brand-centric phenomenon; showing how non-mimetic excitement emerges in marketplace contexts; highlighting the implications for experiential and brand community marketers; and positioning the branded carnival within a broader cultural gravitation towards non-mimetic behaviour opposing marketplace ideology. Finally, limitations are discussed, and directions for further research are sugges...

Direct digital manufacture and additive manufacture have allowed designers the ability to design components without the design limitations witnessed in subtractive manufacturing process routes. In particular, designers can now design parts that fully utilize material usage resulting in a more sustainable and environmentally friendly application of manufacturing technology. Within this context, designing and manufacturing bio-inspired components have the potential to increase both component functionality and optimize material usage. One such area of biomimicry with advantageous strength-to-weight ratio can be found in hedgehog spines. Within this study, hedgehog spines were redesigned to facilitate production through additive manufacture. In addition, with the use of finite element analysis to quantify the resulting compressive characteristics, the optimal internal geometry and septa spacing were determined. Also, a design of experiments study was conducted to determine which design features have the greatest influence on the resulting stress in the spine. The analysis concluded that the combination of longitudinal stiffeners and equally spaced septa give the spine its superior compressive strength.

The issue of chronic loneliness has been described as the new epidemic affecting modern society. The association between loneliness with poorer health outcomes has been well established. However, the specific issue of those reporting loneliness in rural areas has received less attention and debate. This symposium illustrates the challenges faced by seniors in rural settings in both the USA and Europe. It shines a spotlight on environmental, gender, housing, LGBTQ community, as well as mental health in rural areas in a bid to increase understanding, debate and discussion. The symposium aims to answer the question: are there particular characteristics of rural loneliness that may have implications for public health and community practice? Burholt and colleagues use data from the UK (rural Wales) to examine individual and situational risks for social loneliness and emotional loneliness. While Maiden et al in the USA study the differential experiences of men and women through a structural lens. Wiese and Williams provide deep description of the lived experience of seniors in rural social housing communities and their coping strategies. Guest uses state wide data from Kentucky to uncover the impact that loneliness has on marginalized groups and focuses on LGBTQ experiences in rural areas. Finally Jennings concludes with a community-based education program used to improve psychological well-being amongst rural elders. This interdisciplinary symposium provides a strong basis to help guide applied approaches to addressing and preventing loneliness in rural communities among older people.

The inaccessibility of living bone marrow (BM) hampers the study of its pathophysiology under myelotoxic stress induced by drugs, radiation or genetic mutations. Here, we show that a vascularized human BM-on-a-chip (BM chip) supports the differentiation and maturation of multiple blood cell lineages over 4 weeks while improving CD34

While rhizosphere bacteria hold the potential to improve plant health and fitness, little is known about the bacterial genes required to evade host immunity. Using a model system consisting of Arabidopsis and a beneficial Pseudomonas sp. isolate, we identified bacterial genes required for both rhizosphere fitness and for evading host immune responses. This work advances our understanding of how evasion of host defenses contributes to survival in the rhizosphere., Pseudomonas fluorescens and related plant root (“rhizosphere”)-associated species contribute to plant health by modulating defenses and facilitating nutrient uptake. To identify bacterial fitness determinants in the rhizosphere of the model plant Arabidopsis thaliana, we performed a high-throughput transposon sequencing (Tn-Seq) screen using the biocontrol and growth-promoting strain Pseudomonas sp. WCS365. The screen, which was performed in parallel on wild-type and immunocompromised Arabidopsis plants, identified 231 genes that increased fitness in the rhizosphere of wild-type plants. A subset of these genes decreased fitness in the rhizosphere of immunocompromised plants. We hypothesized that these genes might be involved in avoiding plant defenses and verified 7 Pseudomonas sp. WCS365 candidate genes by generating clean deletions. We found that two of these deletion mutants, ΔmorA (encoding a putative diguanylate cyclase/phosphodiesterase) and ΔspuC (encoding a putrescine aminotransferase), formed enhanced biofilms and inhibited plant growth. We found that mutants ΔspuC and ΔmorA induced pattern-triggered immunity (PTI) as measured by induction of an Arabidopsis PTI reporter and FLS2/BAK1-dependent inhibition of plant growth. We show that MorA acts as a phosphodiesterase to inhibit biofilm formation, suggesting a possible role in biofilm dispersal. We found that both putrescine and its precursor arginine promote biofilm formation that is enhanced in the ΔspuC mutant, which cannot break down putrescine, suggesting that putrescine might serve as a signaling molecule in the rhizosphere. Collectively, this work identified novel bacterial factors required to evade plant defenses in the rhizosphere.

Introduction The aim of this study is to determine if simulated 3D vision improves the speed and accuracy of laparoscopic phantom tasks in laparoscopically naive subjects. Methods Thirty laparoscopically naive subjects were divided into matched groups according to age, sex, hand dominance and initial scores on a standardised visio-spatial test. Laprotrain © laparoscopic simulators were used, one attached to the standard 2D monitor and the other to a simulated 3D monitor and 3D glasses were worn by the subjects in this group. Five standardised laparoscopic tasks were developed and the subjects underwent testing on four separate occasions with more than 24 h between sessions. The subjects were timed for each task and errors were recorded by two independent observers. In the second part of the study, subjects switched to the opposite group and task times and errors were again recorded. Statistical differences between groups were calculated using student t-test and Fisher's exact test. Results There were fifteen subjects in each group with no significant difference in demographic or psychometric variables. The mean time to complete the tasks was faster in the 3D group compared with the 2D group. There was a lower rate of errors noted in the 3D group compared with the 2D group but this only reached statistical significance in two of the five laparoscopic tasks. In the crossover study, subjects who had trained on simulated 3D had better task times and fewer errors compared to those who had trained on 2D simulators. Discussion & conclusion Training on a simulated 3D model (compared to standard 2D) allows trainees to reach proficiency sooner.

Contemporary culture is characterized by individual and societal efforts to limit exposure to risk. Paradoxically, many consumers actively pursue high-risk consumption experiences. High-risk consumption, coupled with a lack of consumption-orientated information, amplifies consumer vulnerability. However, consumer-to-consumer information sharing can help reduce unwarranted risk and enhance consumption context control. This study investigates the ecstasy “market maven crowd”: an online community anonymously bound by acts of collective market mavenism intended to address the void of market information and reduce the risks thereof. Acts of collective market mavenism include the assimilation and dissemination of scientific ecstasy pill content reports and personal ecstasy consumption tales. The diffusion of market-orientated information provides consumers with an opportunity to identify, and avert, the serious health risks intrinsic to ecstasy consumption and assert consumption context control. Collaborative market mavenism fosters market policing, which enhances the safety structures of the unregulated ecstasy market. This study contributes to marketing and consumer research by developing an understanding of how consumers collectively adapt to risk online; displaying market mavenism as an innovative framework to examine online consumer-to-consumer information sharing; showing how Internet technologies facilitate the emergence of market maven crowds; and providing marketers with guidelines for approaching market maven crowds. Finally, the author discusses the societal implications arising and suggests directions for future research.

Mounting evidence shows that functional constipation contributes to increased healthcare utilization, impairment in quality of life, and lost work productivity. Among those with functional constipation, relatively small dietary changes may alleviate symptoms and result in considerable constipation-related healthcare cost savings. The study objective was to estimate the economic impact of increased dietary fibre consumption on direct medical costs associated with constipation from a payer perspective. A decision-analytic spreadsheet model was created to perform the analysis. Literature searches identified sources for input parameters, including prevalence of functional constipation, dietary fibre intakes, proportion of the population meeting recommended intakes, and the percentage that would be expected to benefit from increased dietary fibre consumption. The model assumes that 25% of adults make no change in fibre intake, 25% increase intake by 3 g/day, 15% increase intake by 4 g/day, 25% increase intake by 5 g/day, and 10% increase intake by 11 g/day. A dose-response analysis of published data was conducted to estimate the percent reduction in constipation prevalence per 1 g/day increase in dietary fibre intake. Annual direct medical costs for constipation were derived from the literature and updated to 2014. Sensitivity analyses explored robustness of the model. Under base case assumptions, annual cost savings were estimated at ?127,037,383 in the United Kingdom, €8,791,992 / ?7,244,513 in Ireland, and €121,699,804 in Spain. Increasing dietary fibre consumption is associated with considerable cost savings, with these estimates being conservative given the exclusion of lost productivity costs in the model.

Plant-associated soil microbes are important mediators of plant defence responses to diverse above-ground pathogen and insect challengers. For example, closely related strains of beneficial rhizosphere Pseudomonas spp. can induce systemic resistance (ISR), systemic susceptibility (ISS) or neither against the bacterial foliar pathogen Pseudomonas syringae pv. tomato DC3000 (Pto DC3000). Using a model system composed of root-associated Pseudomonas spp. strains, the foliar pathogen Pto DC3000 and the herbivore Trichoplusia ni (cabbage looper), we found that rhizosphere-associated Pseudomonas spp. that induce either ISS and ISR against Pto DC3000 all increased resistance to herbivory by T. ni. We found that resistance to T. ni and resistance to Pto DC3000 are quantitative metrics of the jasmonic acid (JA)/salicylic acid (SA) trade-off and distinct strains of rhizosphere-associated Pseudomonas spp. have distinct effects on the JA/SA trade-off. Using genetic analysis and transcriptional profiling, we provide evidence that treatment of Arabidopsis with Pseudomonas sp. CH267, which induces ISS against bacterial pathogens, tips the JA/SA trade-off towards JA-dependent defences against herbivores at the cost of a subset of SA-mediated defences against bacterial pathogens. In contrast, treatment of Arabidopsis with the ISR strain Pseudomonas sp. WCS417 disrupts JA/SA antagonism and simultaneously primes plants for both JA- and SA-mediated defences. Our findings show that ISS against the bacterial foliar pathogens triggered by Pseudomonas sp. CH267, which is a seemingly deleterious phenotype, may in fact be an adaptive consequence of increased resistance to herbivory. Our work shows that pleiotropic effects of microbiome modulation of plant defences are important to consider when using microbes to modify plant traits in agriculture.

Wheat bran is a concentrated source of insoluble fibre. Fibre intakes are generally lower than recommendations. This paper reviews the physiological effects of wheat bran and the health benefits it may provide in terms of the prevention of diseases such as colon and breast cancers, cardiovascular disease, obesity and gastrointestinal diseases. In recognition of the weight of evidence, the European Food Safety Authority has recently approved two health claims for wheat bran and gastrointestinal health.

This paper explores the processes contributing to the genesis of a brand community. This ethnographic study focuses on the Beamish brand community. The Beamish beer product is a niche brand only available consistently in the locality of Cork city, Ireland. Evidence from this study shows that a collective conversion experience is foundational to the emergence of this brand community. Following this initial conversion experience, the brand community attempts to maintain the transcendent experience through practices of sacralisation maintenance. Sacralisation is maintained through the playful rituals and virtual play the community members enact. The mutual willingness of the converted to participate in these various forms of playful rituals has been a key role in the reification of the Beamish brand community. Finally, suggestions are made as to how brand management should best approach the initial attempts at brand-community formation.

Hunter-Schreger bands are an optical phenomenon observed in mammalian tooth enamel. Familiar to all current and former students of dental histology, this optical phenomenon appears as alternating patterns of dark and light bands when cut enamel is viewed under reflected light. The discovery of this important feature of mammalian enamel has been historically credited to two eighteenth-century investigators, Hunter and Schreger. A re-evaluation of the evidence would suggest that the bands were observed almost seventy years earlier by a French scientist, Gabriel-Philippe de la Hire, and subsequently confirmed by the famous French dentist Pierre Fauchard. This article reviews the contribution of de la Hire, as well as that of Fauchard, Hunter and Schreger, to the early recognition among the scientific community of what would now be referred to as 'enamel microstructure'.

Hunter-Schreger Bands (HSBs) are an optical phenomenon visualised when a cut or fractured enamel surface is viewed under reflected light. These bands demonstrate the synchronous decussation of individual or groups of enamel prisms. While the role of HSB patterns has been investigated in comparative anatomical studies, until recently there has been little consideration of HSB patterns in human teeth. The aim of this paper is to consider the significance of HSB patterns in the human dentition and in relation to clinical dentistry. It is concluded that within the human dentition, HSB patterns have evolved to optimise resistance to attrition, abrasion and tooth fracture. It appears that certain aspects of HSB packing densities and distributions have beneficial roles in enamel bonding. Hunter-Schreger Band patterns seem to passively facilitate conditions such as abfraction and cracked tooth syndrome.

There are reports in the literature of the various dental features of hypophosphatasia, especially where it affects the deciduous dentition. The descriptions include both the manifestations of the disorder and the subsequent patterns of tooth loss. There are fewer descriptions of the effects of hypophosphatasia on the permanent dentition and little information on the subsequent prosthodontic management of these patients, particularly in relation to the use of dental implants. The aim of this paper was to review the literature on the dental effects of hypophosphatasia, present two cases and describe how one of those patients, a young adult, was successfully rehabilitated using dental implants. That latter patient's pattern of tooth loss as well as some histological and scanning electron microscopic findings of root cementum from the other case is also described.

Idiopathic toe walking (ITW) is defined as one who is neurologically normal but demonstrates a preference for walking on the toes. It is a diagnosis of exclusion so differential diagnoses such as cerebral palsy, neuropathy or myopathy must be ruled out. A review of 102 patients attending a gait laboratory with a presumptive diagnosis of ITW found that gait analysis data agreed with this diagnosis in 81 (79.4%) of cases while the remaining 21 (20.6%) were not typical of this diagnosis. The features found to be significantly different between the groups were Babinski response, fast stretch of the gastrocnemius, knee flexion at initial contact and asymmetry at the ankles during gait. This study highlights that clinical gait analysis can be a useful, non-invasive means of diagnosing idiopathic toe walking and recommending appropriate intervention based on clinical and dynamic assessment of calf tightness.

The values for 'mild', 'moderate' and 'severe' urinary incontinence have not been determined for the 24-hour pad test. To define these values, a prospective observational study was performed on 110 women with the primary symptom of urinary incontinence. Consenting women performed two 1-hour pad tests one week apart, and seven 24-hour pad tests for seven consecutive days. The 1-hour pad test definitions for mild, moderate and severe were translated to centiles, and used to categorise the 24-hour test values. This revealed that the range for 'mild incontinence' was between 1.3 and 20 g, 'moderate incontinence' ranged from 21 to 74 g, and 'severe incontinence' was defined as 75 g or more in 24 hours. Severity of leakage was analysed in relation to urodynamic diagnosis, age, parity and pelvic floor muscle strength. Increasing severity was associated with increasing age and parity. Women with detrusor overactivity were most likely to have severe leakage. In conclusion, this study defines the three grades of severity for the 24-hour pad test, which may help to guide patients' choice between conservative and surgical treatment and is useful for stratified randomisation of controlled trial participants.