Low risk management intervention: Limited impact of remedial tillage on net ecosystem carbon balance at a commercial Miscanthus plantation.

Perennial bioenergy crops are a key tool in decarbonizing global energy systems, but to ensure the efficient use of land resources, it is essential that yields and crop longevity are maximized. Remedial shallow surface tillage is being explored in commercial Miscanthus plantations as an approach to reinvigorate older crops and to rectify poor establishment, improving yields. There are posited links, however, between tillage and losses in soil carbon (C) via increased ecosystem C fluxes to the atmosphere. As Miscanthus is utilized as an energy crop, changes in field C fluxes need to be assessed as part of the C balance of the crop. Here, for the first time, we quantify the C impacts of remedial tillage at a mature commercial Miscanthus plantation in Lincolnshire, United Kingdom. Net ecosystem C production based on eddy covariance flux observations and exported yield totalled 12.16 Mg C ha-1 over the 4.6 year period after tillage, showing the site functioned as a net sink for atmospheric carbon dioxide (CO2). There was no indication of negative tillage induced impacts on soil C stocks, with no difference 3 years post tillage in the surface (0-30 cm) or deep (0-70 cm) soil C stocks between the tilled Miscanthus field and an adjacent paired untilled Miscanthus field. Comparison to historic samples showed surface soil C stocks increased by 11.16 ± 3.91 Mg C ha-1 between pre (October 2011) and post tillage sampling (November 2016). Within the period of the study, however, the tillage did not result in the increased yields necessary to "pay back" the tillage induced yield loss. Rather the crop was effectively re-established, with progressive yield increases over the study period, mirroring expectations of newly planted sites. The overall impacts of remedial tillage will depend therefore, on the longer-term impacts on crop longevity and yields.

Isolated Ocular Relapse of Acute Myeloid Leukaemia Post Allogeneic Stem Cell Transplant.

We present a rare case of a 39-year-old female with extramedullary relapse of acute myeloid leukaemia (AML) isolated to the left eye 2 months post allogeneic haematopoietic stem cell transplant. She initially presented with painless left eye erythema, swelling, and visual impairment. Initial ophthalmology review revealed conjunctival chemosis, raised intraocular pressure, and serous retinal detachments. She was initially treated for suspected orbital cellulitis with intravenous antibiotic and antifungal therapy but clinically progressed so was then treated with intravenous corticosteroids. One week later, she progressed to angle-closure glaucoma with development of a hypopyon and an enlarging subconjunctival mass. She proceeded to urgent subconjunctival biopsy and drainage of subretinal fluid which confirmed extramedullary relapse of AML. Notably, further investigation found no evidence of bone marrow or central nervous system relapse. She proceeded to localized radiotherapy with gradual resolution of the subconjunctival mass and serous retinal detachment and was for consideration of donor lymphocyte infusions and azacitidine therapy; unfortunately, she developed respiratory sepsis and passed away despite maximal efforts. This case represents a rare and unusual presentation of isolated ocular extramedullary relapse of AML and emphasises the importance of early ophthalmology involvement and tissue biopsy when there is high clinical suspicion of the disease.

Neuroimaging findings in adolescent gaming disorder: a systematic review.

OBJECTIVES: Gaming disorder is a growing concern affecting adolescents, exacerbated by the impact of recent COVID-19 restrictions. The World Health Organization has recently included gaming disorder in the 11th International Classification of Diseases (ICD-11). However, there is still an ongoing debate about the validity and reliability of the proposed clinical criteria, despite growing neurobiological evidence in this cohort. Systematic reviews in this area have focused mainly on adults or mixed adult/adolescent populations. Therefore, this systematic review explored the neuroimaging literature in adolescents (under 18 years old) with gaming disorder. METHODS: Using PRISMA 2020 guidelines, 3288 primary studies were identified from PubMed, CINAHL Plus, PsycINFO and Web of Science. After applying inclusion and exclusion criteria (appropriate title, abstract, comparison group used within study, English-language, neuroimaging and mean age under 18), 24 studies were included in this review. RESULTS: Functional and structural brain alterations in adolescent gaming disorder were noted across several imaging modalities, including electroencephalogram (EEG), functional magnetic resonance imaging (fMRI) and structural magnetic resonance imaging (MRI). Compared with healthy controls, adolescents with gaming disorder demonstrated neurological changes comparable to substance addiction, namely impairments in emotional regulation, reward-seeking, inhibition and increased risky decision-making. Positive brain adaptations in the areas of visuospatial processing and memory were observed. CONCLUSIONS: A number of key brain regions are affected in adolescent gaming disorder. These findings can help clinicians understand adolescent presentations with gaming disorder from a neurobiological perspective. Future studies should focus on forming a robust neurobiological and clinical framework for adolescent gaming disorder.

Species selection determines carbon allocation and turnover in Miscanthus crops: Implications for biomass production and C sequestration.

Growing Miscanthus species and hybrids has received strong scientific and commercial support, with the majority of the carbon (C) modelling predictions having focused on the high-yield, sterile and noninvasive hybrid Miscanthus × giganteus. However, the potential of other species with contrasting phenotypic and physiological traits has been seldom explored. To better understand the mechanisms underlying C allocation dynamics in these bioenergy crops, we pulse-labelled (13CO2) intact plant-soil systems of Miscanthus × giganteus (GIG), Miscanthus sinensis (SIN) and Miscanthus lutarioriparius (LUT) and regularly analysed soil respiration, leaves, stems, rhizomes, roots and soils for up to 190 days until leaf senescence. A rapid isotopic enrichment of all three species was observed after 4 h, with the amount of 13C fixed into plant biomass being inversely related to their respective standing biomass prior to pulse-labelling (i.e., GIG < SIN < LUT). However, both GIG and LUT allocated more photoassimilates in the aboveground biomass (leaves+stems = 78 % and 74 %, respectively) than SIN, which transferred 30% of fixed 13C in its belowground biomass (rhizomes+roots). Although less fixed 13C was recovered from the soils (<1 %), both rhizospheric and bulk soils were signficantly more enriched under SIN and LUT than under GIG. Importantly, the soils under SIN emitted less CO2, which suggests it could be the best choice for reaching C neutrality. These results from this unique large-scale study indicate that careful species selection may hold the success for reaching net GHG mitigation.

A controlled evaluation of the effect of social prescribing programs on loneliness for adults in Queensland, Australia (protocol).

BACKGROUND: In social prescribing, link workers support individuals whose persistent health problems are exacerbated by loneliness by connecting them to community-based social activities. This approach is well established in the UK and is gaining attention in Australia. However, a major limitation of research to date has been a lack of theoretically informed and rigorous evaluations of social prescribing. We will address these points in this study, applying a social identity framework to examine the effects of group-based social prescribing (SP) activity compared to primary care treatment as usual (TAU). METHODS: Ninety participants experiencing loneliness recruited from primary care services and community centres across five sites in Southeast Queensland will be assigned to one of two conditions (SP, TAU) and assessed at two timepoints (baseline, + 8 weeks). Individuals will be aged 18 years and over, have sufficient English language skills to provide consent, and at the time of recruitment they will not be experiencing acute symptoms or social issues that require urgent intervention. Primary outcomes are loneliness, mental well-being, and health service use (total number of GP, hospital, and allied health visits in the past 3 months). Secondary outcomes will assess social group processes, including number of important social groups, new group identification, multiple identity compatibility, and group-based support and emotion regulation. DISCUSSION: This study will provide comprehensive data about the extent to which, and how, social prescribing to community-based group activities may help people to feel less lonely, more socially integrated, and healthy over the first 8 weeks. If effective, this social identity-informed model of social prescribing can be disseminated in communities across Australia. TRIAL REGISTRATION: ANZCTR, Registered 8 June 2022 - Retrospectively registered, https://www.anzctr.org.au/ACTRN12622000801718.aspx.

Overriding water table control on managed peatland greenhouse gas emissions.

Global peatlands store more carbon than is naturally present in the atmosphere1,2. However, many peatlands are under pressure from drainage-based agriculture, plantation development and fire, with the equivalent of around 3 per cent of all anthropogenic greenhouse gases emitted from drained peatland3-5. Efforts to curb such emissions are intensifying through the conservation of undrained peatlands and re-wetting of drained systems6. Here we report eddy covariance data for carbon dioxide from 16 locations and static chamber measurements for methane from 41 locations in the UK and Ireland. We combine these with published data from sites across all major peatland biomes. We find that the mean annual effective water table depth (WTDe; that is, the average depth of the aerated peat layer) overrides all other ecosystem- and management-related controls on greenhouse gas fluxes. We estimate that every 10 centimetres of reduction in WTDe could reduce the net warming impact of CO2 and CH4 emissions (100-year global warming potentials) by the equivalent of at least 3 tonnes of CO2 per hectare per year, until WTDe is less than 30 centimetres. Raising water levels further would continue to have a net cooling effect until WTDe is within 10 centimetres of the surface. Our results suggest that greenhouse gas emissions from peatlands drained for agriculture could be greatly reduced without necessarily halting their productive use. Halving WTDe in all drained agricultural peatlands, for example, could reduce emissions by the equivalent of over 1 per cent of global anthropogenic emissions.

Eating disorder services for young people in Ireland: perspectives of service providers, service users and the general adolescent population.

OBJECTIVES: This paper illuminates how national eating disorder (ED) policy translates into day-to-day practice by exploring how ED services are experienced by those who deliver and use them. METHODS: A mixed-methods approach was used, which combined qualitative and quantitative techniques. The paper collates data from three studies: (i) an interview study exploring the lived experiences of young people with EDs (n=8), their parents (n=5) and their healthcare professionals (n=3); (ii) a national survey of health professionals' perspectives on existing ED services (n=171); (iii) a nationwide survey of secondary-school students' eating concerns and patterns of help-seeking (n=290). RESULTS: The qualitative interviews with young people and their parents revealed feelings of isolation and helplessness. Young people expressed interest in patient support groups, while parents desired greater support for the family unit. Parents were highly critical of available services, particularly in relation to access. These criticisms were echoed in the survey of healthcare professionals, who reported many barriers to delivering effective care. Clinicians were almost unanimous in calling for care pathways to be clarified via a standardised treatment protocol. The survey of adolescents indicated widespread reluctance to seek help regarding eating concerns: over one-third expressed concern about their own eating habits, but half of these had not divulged their concerns to anyone. Participants' preferred pathways of help-seeking revolved around family and friends, and adolescents were unsure about routes of access to professional support. CONCLUSIONS: The research demonstrates that many aspects of national ED policy have not been implemented in practice. The paper highlights specific gaps and suggests ways they can be redressed.

Direct isotopic evidence of biogenic methane production and efflux from beneath a temperate glacier.

The base of glaciers and ice sheets provide environments suitable for the production of methane. High pressure conditions beneath the impermeable 'cap' of overlying ice promote entrapment of methane reserves that can be released to the atmosphere during ice thinning and meltwater evacuation. However, contemporary glaciers and ice sheets are rarely accounted for as methane contributors through field measurements. Here, we present direct field-based evidence of methane production and release from beneath the Icelandic glacier Sólheimajökull, where geothermal activity creates sub-oxic conditions suited to methane production and preservation along the meltwater flow path. Methane production at the glacier bed (48 tonnes per day, or 39 mM CH4 m-2 day-1), and evasion to the atmosphere from the proglacial stream (41 tonnes per day, or 32 M CH4 m-2 day-1) indicates considerable production and release to the atmosphere during the summer melt season. Isotopic signatures (-60.2‰ to -7.6‰ for δ13CCH4 and -324.3‰ to +161.1‰ for DCH4), support a biogenic signature within waters emerging from the subglacial environment. Temperate glacial methane production and release may thus be a significant and hitherto unresolved contributor of a potent greenhouse gas to the atmosphere.

Stigma and treatment of eating disorders in Ireland: healthcare professionals' knowledge and attitudes.

OBJECTIVES: This study examines aspects of healthcare professionals' knowledge and attitudes about eating disorders (EDs), which might impede the effective detection or treatment of EDs in Ireland. METHODS: A total of 1,916 healthcare professionals were invited to participate in a web-based survey. Participants were randomly allocated to view one of five vignettes depicting a young person with symptoms consistent with anorexia nervosa, bulimia nervosa, binge-eating disorder, depression or type 1 diabetes. Study-specific questions examined participants' responses to the vignettes and ED knowledge and experience. RESULTS: In total, 171 clinicians responded (9% response rate). Participants had an average of 15.8 years of clinical experience (s.d.=9.2) and included psychiatrists, GPs, psychologists and counsellors. Although participants' knowledge of EDs was moderately good overall, responses showed poor recognition of the symptoms of EDs compared with depression [χ 2 (4, n=127)=20.17, p<0.001]. Participants viewed EDs as chronic disorders that primarily affected females. Participants believed that clinicians like working with patients with depression and diabetes more than with AN patients [F (4,101)=5.11, p=0.001]. Among the professionals surveyed, psychiatrists were the most knowledgeable about EDs [F (4,82)=9.18, p<0.001], and were more confident in their ability to diagnose and treat EDs than professionals of all other disciplines, except psychologists [F (4,85)=8.99, p<0.001]. Psychiatrists were also the most pessimistic about ED patients' long-term life prospects [χ 2 (4, n=65)=15.84, p=0.003]. CONCLUSIONS: This study recommends that specific attention should be given to EDs in professional educational programmes across healthcare disciplines. This training should not be restricted to improving healthcare professionals' knowledge of EDs, but should also strive to increase service-providers' awareness of how their own potentially stigmatising attitudes can undermine engagement with treatment.

Adolescents' and parents' views of Child and Adolescent Mental Health Services (CAMHS) in Ireland.

Service user involvement is essential for quality care in the Child and Adolescent Mental Health Services (CAMHS). This study was conducted to explore adolescents' and parents' experiences of CAMHS in relation to accessibility, approachability and appropriateness. This study used a descriptive qualitative design, and focus groups and single interviews were conducted with adolescents (n = 15) and parents (n = 32) from three mental health clinics. Data were analysed using thematic analysis. Accessing mental health services was a challenging experience for many parents and adolescents due to knowledge deficit, lack of information and limited availability of specialist services. Some parents and adolescents reported positive experiences while others reported negative experiences. They expressed a need for more information, involvement in decision making, flexible scheduling of appointments, school support and parent support groups. The nature and quality of the relationship with staff was critical to positive experience with the service; therefore, frequent changes of medical staff was disruptive. Mental health nurses can play a vital role in ensuring continuity, assessing adolescents' participation preferences and advocating for their information needs with other members of the interdisciplinary team.

Who is in the transition gap? Transition from CAMHS to AMHS in the Republic of Ireland.

OBJECTIVE: The ITRACK study explored the process and predictors of transition between Child and Adolescent Mental Health Services (CAMHS) and Adult Mental Health Services (AMHS) in the Republic of Ireland. METHOD: Following ethical approval, clinicians in each of Ireland's four Health Service Executive (HSE) areas were contacted, informed about the study and were invited to participate. Clinicians identified all cases who had reached the transition boundary (i.e. upper age limit for that CAMHS team) between January and December 2010. Data were collected on clinical and socio-demographic details and factors that informed the decision to refer or not refer to the AMHS, and case notes were scrutinised to ascertain the extent of information exchanged between services during transition. RESULTS: A total of 62 service users were identified as having crossed the transition boundary from nine CAMHS [HSE Dublin Mid-Leinster (n=40, 66%), HSE South (n=18, 30%), HSE West (n=2, 3%), HSE Dublin North (n=1, 2%)]. The most common diagnoses were attention deficit hyperactivity disorder (ADHD; n=19, 32%), mood disorders (n=16, 27%), psychosis (n=6, 10%) and eating disorders (n=5, 8%). Forty-seven (76%) of those identified were perceived by the CAMHS clinician to have an 'on-going mental health service need', and of these 15 (32%) were referred, 11 (23%) young people refused and 21 (45%) were not referred, with the majority (12, 57%) continuing with the CAMHS for more than a year beyond the transition boundary. Young people with psychosis were more likely to be referred [χ 2 (2, 46)=8.96, p=0.02], and those with ADHD were less likely to be referred [χ 2 (2, 45)=8.89, p=0.01]. Being prescribed medication was not associated with referral [χ 2 (2, 45)=4.515, p=0.11]. In referred cases (n=15), there was documented evidence of consent in two cases (13.3%), inferred in another four (26.7%) and documented preparation for transition in eight (53.3%). Excellent written communication (100%) was not supported by face-to-face planning meetings (n=2, 13.3%), joint appointments (n=1, 6.7%) or telephone conversations (n=1, 6.7%) between corresponding clinicians. CONCLUSIONS: Despite perceived on-going mental health (MH) service need, many young people are not being referred or are refusing referral to the AMHS, with those with ADHD being the most affected. CAMHS continue to offer on-going care past the transition boundary, which has resource implications. Further qualitative research is warranted to understand, in spite of perceived MH service need, the reason for non-referral by the CAMHS clinicians and refusal by the young person.

Survey examining the views of Adult Psychiatry Consultants and Senior Registrars regarding ADHD.

OBJECTIVES: Attention deficit hyperactivity disorder (ADHD) persists into adulthood in ∼2/3 of patients, yet services for adults are lacking in Ireland. This may involve negative attitudes and beliefs as to the validity of ADHD or lack of knowledge and training in its treatment. The objectives of this study are to explore the views of Adult Psychiatrists regarding ADHD knowledge and the treatment options available and pursued in Ireland. METHODS: A questionnaire was constructed based on the stated aims of the study, and was either posted, emailed or handed to 400 Consultants and Senior Registrars throughout the Republic of Ireland between February and December 2011. A total of 92 questionnaires were returned (23%); one was excluded from analysis due to insufficient information entered by the respondent. RESULTS: Seventy-five per cent of respondents correctly estimated the prevalence rates of adult ADHD to be under 3%, but stated it is currently under-diagnosed (77%). Seventy-four per cent indicated that Adult ADHD should be a diagnostic category in the Diagnostic and Statistical Manual, 5th Edition (DSM V). Sixty-six per cent of respondents were willing to accept referrals of childhood ADHD for ongoing care and a similar number for new ADHD assessments (61%). Less than half (42%) surveyed had actually diagnosed ADHD and of these, only 33% felt confident in managing ADHD in their patients. CONCLUSIONS: Although there is a general willingness to offer services for new and existing ADHD cases and a recognition that Adult ADHD is valid and under-diagnosed, the low confidence levels when treating ADHD and the perception of under-diagnosis suggests a role for further training and links between child and adult services.

American College of Rheumatology classification criteria for Sjögren's syndrome: a data-driven, expert consensus approach in the Sjögren's International Collaborative Clinical Alliance cohort.

OBJECTIVE: We propose new classification criteria for Sjögren's syndrome (SS), which are needed considering the emergence of biologic agents as potential treatments and their associated comorbidity. These criteria target individuals with signs/symptoms suggestive of SS. METHODS: Criteria are based on expert opinion elicited using the nominal group technique and analyses of data from the Sjögren's International Collaborative Clinical Alliance. Preliminary criteria validation included comparisons with classifications based on the American­European Consensus Group (AECG) criteria, a model-based "gold standard"obtained from latent class analysis (LCA) of data from a range of diagnostic tests, and a comparison with cases and controls collected from sources external to the population used for criteria development. RESULTS: Validation results indicate high levels of sensitivity and specificity for the criteria. Case definition requires at least 2 of the following 3: 1) positive serum anti-SSA and/or anti-SSB or (positive rheumatoid factor and antinuclear antibody titer >1:320), 2) ocular staining score >3, or 3) presence of focal lymphocytic sialadenitis with a focus score >1 focus/4 mm2 in labial salivary gland biopsy samples. Observed agreement with the AECG criteria is high when these are applied using all objective tests. However, AECG classification based on allowable substitutions of symptoms for objective tests results in poor agreement with the proposed and LCA-derived classifications. CONCLUSION: These classification criteria developed from registry data collected using standardized measures are based on objective tests. Validation indicates improved classification performance relative to existing alternatives, making them more suitable for application in situations where misclassification may present health risks.

Gully hotspot contribution to landscape methane (CH4) and carbon dioxide (CO2) fluxes in a northern peatland.

Peatlands are long term carbon catchments that sink atmospheric carbon dioxide (CO(2)) and source methane (CH(4)). In the uplands of the United Kingdom ombrotrophic blanket peatlands commonly exist within Calluna vulgaris (L.) dominated moorland ecosystems. These landscapes contain a range of topographical features that influence local hydrology, climate and plant community composition. In this study we examined the variation in ecosystem CO(2) respiration and net CH(4) fluxes from typical plant-soil systems in dendritic drainage gullies and adjacent blanket peat during the growing season. Typically, Eriophorum spp., Sphagnum spp. and mixed grasses occupied gullies while C. vulgaris dominated in adjacent blanket peat. Gross CO(2) respiration was highest in the areas of Eriophorum spp. (650+/-140 mg CO(2) m(-2) h(-1)) compared to those with Sphagnum spp. (338+/-49 mg CO(2) m(-2) h(-1)), mixed grasses (342+/-91 mg CO(2) m(-2) h(-1)) and C. vulgaris (174+/-63 mg CO(2) m(-2) h(-1)). Measurements of the net CH(4) flux showed higher fluxes from the Eriophorum spp (2.2+/-0.6 mg CH(4) m(-2) h(-1)) locations compared to the Sphagnum spp. (0.6+/-0.4 mg CH(4) m(-2) h(-1)), mixed grasses (0.1+/-0.1 mg CH(4) m(-2) h(-1)) and a negligible flux detected from C. vulgaris (0.0+/-0.0 mg CH(4) m(-2) h(-1)) locations. A GIS approach was applied to calculate the contribution of gullies to landscape scale greenhouse gas fluxes. Findings from the Moor House National Nature Reserve in the UK showed that although gullies occupied only 9.3% of the total land surface, gullies accounted for 95.8% and 21.6% of the peatland net CH(4) and CO(2) respiratory fluxes, respectively. The implication of these findings is that the relative contribution of characteristic gully systems need to be considered in estimates of landscape scale peatland greenhouse gas fluxes.

Exposure of human corneal epithelial cells to contact lenses in vitro suppresses the upregulation of human beta-defensin-2 in response to antigens of Pseudomonas aeruginosa.

Bacterial keratitis is a sight-threatening complication of contact lens wear, and Pseudomonas aeruginosa is a commonly isolated pathogen. The mechanisms by which lenses predispose the cornea to P. aeruginosa infection are unknown. Corneal epithelial cells express numerous innate defenses, some of which have bactericidal effects against P. aeruginosa. One of these is human beta-defensin-2 (hBD-2), which is upregulated in response to lipopolysaccharide or flagellin antigens. We hypothesized that prior exposure of corneal epithelia to a contact lens would interfere with upregulation of hBD-2 in response to P. aeruginosa. A novel in vitro model was used in which cultured human corneal epithelial cells were exposed to a hydrophilic contact lens for up to 3.5 days prior to challenge with a culture supernatant of P. aeruginosa antigens for 6h. Without prior lens exposure, the supernatant caused >2-fold upregulation of hBD-2 mRNA message and expression of hBD-2 peptide. Prior contact lens exposure blocked this upregulation without obvious effects on cell health. Western immunoblot and luciferase reporter studies showed that Pseudomonas-induced hBD-2 upregulation involved MyD88, c-Jun N-terminal kinase and both AP-1 and NF-kappaB transcription factors. Contact lenses did not affect surface expression of Toll-like receptor-2, -4 or -5, but did block antigen activation of AP-1, but not NF-kappaB, transcription factors. These data show that contact lenses can interfere with epithelial defense responses to bacterial antigens in vitro, and if translated in vivo, could help predispose the cornea to infection.

Rapid, continuous cycling and psychiatric co-morbidity in pediatric bipolar I disorder.

OBJECTIVES: The primary purpose of this study was to describe the clinical presentation of bipolar I disorder (BP-I) as it occurs in children and adolescents and to assess whether the manifestations of BP-I were similar in both age groups. METHOD: Ninety youths between the ages of 5 and 17 years meeting full diagnostic symptom criteria for BP-I were included in this study. The diagnosis of BP-I was established for these youths based on the results of a semi-structured diagnostic interview and a clinical assessment by a child and adolescent psychiatrist. The course of a subset of these youngsters' illnesses was assessed using the Life Charting Method (LCM). Data regarding the clinical presentation, longitudinal history, psychiatric co-morbidities and parental psychopathology were also obtained. RESULTS: The clinical presentation of BP-I was similar in children and adolescents. Youths meeting diagnostic criteria for BP-I developed an average of approximately 5.8 of the 7 symptoms of mania during periods of elevated or irritable mood. BP-I was found to be a cyclic disorder characterized by high rates of rapid cycling (50%) with almost no inter-episode recovery. Almost 75% of these subjects also met diagnostic symptom criteria for a disruptive behavior disorder. High rates of mood disorders were found in fathers. CONCLUSIONS: These data suggest that the presentation of juvenile BP-I is a cyclic and valid clinical condition with manifestations on a continuum with the later-onset forms of this illness.

ATP transduces signals from ASGM1, a glycolipid that functions as a bacterial receptor.

The flagella of the Gram-negative bacterium Pseudomonas aeruginosa serve not only for motility but also to bind bacteria to the host cell glycolipid asialoGM1 (ASGM1) through the protein flagellin. This interaction triggers defensive responses in host cells. How this response occurs is unclear because ASGM1 lacks transmembrane and cytoplasmic domains and there is little information about the downstream effectors that connect ASGM1 ligation to the initiation of host defense responses. Here, we show that ASGM1 ligation promotes ATP release from the host cell, followed by autocrine activation of a nucleotide receptor. This response links ASGM1 to cytoplasmic signaling molecules and results in activation of phospholipase C, Ca(2+) mobilization, phosphorylation of a mitogen-activated protein kinase (Erk 1/2), and activation of mucin transcription. These results indicate that bacterial interaction with host cells can trigger autocrine nucleotide signaling and suggest that agents affecting nucleotide receptors may modulate host responses to bacteria.

The Berkeley Contact Lens Extended Wear Study. Part I : Study design and conduct.

OBJECTIVE: The primary aim of the Berkeley Contact Lens Extended Wear Study (CLEWS) was to test the hypotheses that extended wear of rigid gas-permeable (RGP) contact lenses with greater oxygen permeability (Dk) reduces the incidence of contact lens-associated keratopathy (CLAK) and increases the survival rate in RGP extended wear (EW). In this article we describe the clinical trial design in detail, present the results of subject recruitment and retention, and provide the baseline demographic and ocular characteristics of the CLEWS subjects, whose data will be analyzed to address the study aims in a companion article. DESIGN: A randomized, concurrently controlled clinical trial. INTERVENTION: Subjects were fitted with day wear (DW) high-Dk RGP lenses and then adapted to EW. Subjects who adapted to EW were then randomly assigned to either high- or medium-Dk RGP lenses for 12 months of 6-nights/week EW. MAIN OUTCOME MEASURES: Slit-lamp assessment and grading of 17 possible keratopathies, measurement of refractive error and corneal curvature, and symptoms. Follow-up data were collected every 3 months. RESULTS: From 545 subjects entering the DW adaptation phase, 201 adapted to EW and were randomly assigned to medium- or high-Dk lenses for 12 months of EW. The baseline characteristics of the two study groups were similar and did not differ from the 344 DW subjects who failed to adapt to EW. The distributions of oxygen transmissibility for the two study groups were disjoint, indicating that each group received distinctly different levels of hypoxia. CONCLUSIONS: We show that CLEWS was appropriately designed to address the study hypotheses, was conducted with regard for the safety of the subjects, and adhered to rigorous protocols designed to control for bias and ensure the integrity of study data. We establish the internal validity of between-group statistical comparisons and characterize our study population to permit informed evaluation of the applicability of our results to the contact lens-wearing population in general.

The Berkeley Contact Lens Extended Wear Study. Part II : Clinical results.

OBJECTIVE: To describe the principal clinical outcomes associated with 12 months use of rigid gas-permeable (RGP) extended wear contact lenses and address two primary study questions: (1) does extended wear (EW) of high oxygen transmissibility (Dk/t) RGP lenses reduce the incidence of ocular complications, and (2) does the wearing of high-Dk/t lenses reduce the rate of failure to maintain 6-night RGPEW over 12 months? DESIGN: A randomized, concurrently controlled clinical trial. INTERVENTION: Subjects who adapted to EW with high Dk (oxygen permeability) RGP lenses were randomized to either high Dk or medium-Dk RGP lenses for 12 months of 6-night EW. MAIN OUTCOME MEASURES: Contact lens-associated keratopathies (CLAK), changes in refractive error and corneal curvature, and survival in EW. RESULTS: Two hundred one subjects were randomized to medium or high-Dk lenses for 12 months of EW. Sixty-two percent of the subjects in each group completed 12 months of EW; however, the probability of failure was significantly greater for the medium-Dk group. Although the risk of complications was similar for the two groups, the number of CLAK events that led to termination were 16 versus 5 for the medium-Dk and high-Dk groups, respectively. This suggests that the type of adverse response or the inability to reverse an adverse event was different for the group being exposed to the lower oxygen dose. CONCLUSIONS: The level of oxygen available to the cornea has a significant impact on maintaining successful RGP extended contact lens wear, but not on the initial onset of CLAK. The number of clinical events leading to termination was substantially higher for the medium Dk group, which suggests that corneal hypoxia is an important factor in the development of CLAK. Although overnight contact lens wear should be recommended with caution and carefully monitored for early detection of ocular complications, it appears that high-Dk RGP lenses can be a safe and effective treatment for correction of refractive error for most individuals who can adapt to EW.

Management of acute coronary syndromes in the community hospital without cardiac surgical capability: how can access to interventional therapy be improved?

Early coronary artery intervention is emerging as the treatment of choice for patients with high risk acute coronary syndromes (ACS). However, most patients with ACS are admitted to hospitals which do not have ready access to interventional therapy. Extending the benefits of early intervention to this population is problematic at such community hospitals, since this approach would require either emergency transfer to a tertiary center or the performance of angioplasty on-site at hospitals without cardiac surgical capability. A third solution, pre-hospital ambulance triage to interventional centers, is not currently practised in most countries. A growing body of evidence indicates that hospitals without cardiac surgical capability can establish safe and effective primary angioplasty programs. Patients with acute myocardial infarction (AMI) who are randomized to transfer for primary angioplasty without fibrinolytic treatment have fewer major adverse cardiac events than those treated with fibrinolytics alone or fibrinolytics and transfer. In patients with unstable angina (UA) or non-ST-elevation AMI, an early aggressive approach led to a significant reduction in the composite end-point of death, AMI, or rehospitalization for recurrent UA at 6 months with no increase in cost, compared with conservative management. Ongoing trials in Europe indicate that pre-hospital ambulance triage of patients with large AMI to interventional centers can be remarkably rapid, safe, and effective. In order to improve the access of such patients to early intervention, 3 interdependent solutions are proposed:The development of more interventional programs at those hospitals without cardiac surgical facilities that can meet rigorous standards. The development of protocols to insure the early and more frequent transfer of patients with high-risk ACS to interventional centers for coronary angiography and revascularization. The pre-hospital triage of patients with AMI to established heart attack centers with 24-hour, 365-day emergency interventional capability for immediate primary angioplasty (after the model of trauma centers). Universal triage/transfer of all such patients to interventional centers could, however, quickly flood the capability of all tertiary surgical hospitals. With the aging of the 'baby boomers' in the near future, the need for interventional facilities will increase even further. Thus the second and third solutions above will ultimately depend on the first solution. Improving the delivery of interventional therapy to patients with ACS can provide a substantial healthcare benefit to society.