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This retrospective chart review aimed to identify the intersection between young people with Autism Spectrum Disorder (ASD)'s needs and CAMHS inpatient service needs. A retrospective chart review was conducted on all referrals to a CAMHS inpatient unit over three years ( n = 352). Referrals which specified a formal diagnosis or suspected diagnosis of ASD were identified ( n = 111), and basic demographic data were collected. Young people with either a formal or suspected diagnosis of ASD referred to the unit presented with a wide range of co-occurring conditions. Of these young people, 30 were admitted to the unit and only 6 of them were engaged with an ASD specialist service. Young people with diagnosed or suspected ASD were more likely to be admitted if they presented with suicidality. Males with diagnosed or suspected ASD were more likely to have a diagnosis of OCD while females with diagnosed or suspected ASD were more likely to present with eating and feeding disorders and personality development difficulties. Findings highlight the lack of a clear care pathway for young people with co-occurring autism or suspected autism and complex mental health problems., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MOC has declared that they have no competing or potential conflicts of interest. Dr. CG has declared that they have no competing or potential conflicts of interest. JC has declared that they have no competing or potential conflicts of interest. Dr. CS has declared that they have no competing or potential conflicts of interest. Dr. MD has declared that they have no competing or potential conflicts of interest. Dr. FL has declared that they have no competing or potential conflicts of interes.

Background: Ehlers-Danlos Syndrome (EDS) is a rare group of connective tissue disorders and, as such, the diagnosis can often be delayed. While emerging research indicates that there may be adverse psychosocial consequences for the child, little is known about the processes behind such outcomes, including the psychosocial impact of this rare disease on family life., Aims: To extend our understanding, we examined the lived experiences of parenting a child with EDS., Methods: Four parents recruited from a specialist child development clinic participated in semi-structured interviews. Data were analysed using Interpretative Phenomenological Analysis RESULTS: Three superordinate themes were identified: (1) Challenges Associated with hEDS, (2) Interactions with Professionals and (3) "Pulling and Pacing": Life with EDS., Discussion: This is one of the first qualitative studies to gain an insight into the lived experiences of parenting a child with EDS. Findings had systemic implications. Specifically, we demonstrate the need for raising awareness in health and educational professionals about how to better support families to support the child, as well as the importance of promoting effective advocacy skills in parents., Competing Interests: Declaration of Competing Interest The authors report there are no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Bifidobacteria are commonly encountered members of the human gut microbiota that possess the enzymatic machinery necessary for the metabolism of certain plant-derived, complex carbohydrates. In the current study we describe differential growth profiles elicited by a panel of 21 newly isolated Bifidobacterium pseudocatenulatum strains on various plant-derived glycans. Using a combination of gene-trait matching and comparative genome analysis, we identified two distinct xylanases responsible for the degradation of xylan. Furthermore, three distinct extracellular α-amylases were shown to be involved in starch degradation by certain strains of B. pseudocatenulatum . Biochemical characterization showed that all three α-amylases can cleave the related substrates amylose, amylopectin, maltodextrin, glycogen and starch. The genes encoding these enzymes are variably found in the species B. pseudocatenulatum , therefore constituting a strain-specific adaptation to the gut environment as these glycans constitute common plant-derived carbohydrates present in the human diet. Overall, our study provides insights into the metabolism of these common dietary carbohydrates by a human-derived bifidobacterial species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Sanchez-Gallardo, Bottacini, Friess, Esteban-Torres, Somers, Moore, McAuliffe, Cotter and van Sinderen.)

Amber preserves an exceptional record of tiny, soft-bodied organisms and chemical environmental signatures, elucidating the evolution of arthropod lineages and the diversity, ecology, and biogeochemistry of ancient ecosystems. However, globally, fossiliferous amber deposits are rare in the latest Cretaceous and surrounding the Cretaceous-Paleogene (K-Pg) mass extinction. 1 , 2 , 3 , 4 , 5 This faunal gap limits our understanding of arthropod diversity and survival across the extinction boundary. 2 , 6 Contrasting hypotheses propose that arthropods were either relatively unaffected by the K-Pg extinction or experienced a steady decline in diversity before the extinction event followed by rapid diversification in the Cenozoic. 2 , 6 These hypotheses are primarily based on arthropod feeding traces on fossil leaves and time-calibrated molecular phylogenies, not direct observation of the fossil record. 2 , 7 Here, we report a diverse amber assemblage from the Late Cretaceous (67.04 ± 0.16 Ma) of the Big Muddy Badlands, Canada. The new deposit fills a critical 16-million-year gap in the arthropod fossil record spanning the K-Pg mass extinction. Seven arthropod orders and at least 11 insect families have been recovered, making the Big Muddy amber deposit the most diverse arthropod assemblage near the K-Pg extinction. Amber chemistry and stable isotopes suggest the amber was produced by coniferous (Cupressaceae) trees in a subtropical swamp near remnants of the Western Interior Seaway. The unexpected abundance of ants from extant families and the virtual absence of arthropods from common, exclusively Cretaceous families suggests that Big Muddy amber may represent a yet unsampled Late Cretaceous environment and provides evidence of a faunal transition before the end of the Cretaceous., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Eating patterns such as breakfast consumption and fruit and vegetable intake have been associated with academic achievement and cognitive function., Method: The purpose of this study was to learn more about psychological (emotion-driven eating) and behavioral (over-eating) eating patterns and motives, and the roles of body image, academic achievement (reading and math), and social supports (peer acceptance and school attachment), among 378 fourth-grade students (55% boys) from 14 classrooms across 6 schools within a large Midwestern urban area., Results: Results were analyzed through a 2-group (male and female) path analysis. Boys' overeating (R 2  = 9%) was not significantly predicted. Their emotional eating (R 2  = 22.2%) was negatively, significantly predicted by peer acceptance and interaction of peer acceptance and school attachment. Girls' overeating (R 2  = 13.6%) was negatively, significantly predicted by positive body image. Girls' emotional eating (R 2  = 24.1%) was negatively significantly predicted by positive body image, math scores, and peer acceptance., Conclusions: Boys' and girls' eating patterns are differentially affected by their school experiences., (© 2023, American School Health Association.)

There is large potential to increase cycling participation worldwide. Participation in cycling is associated with lower risk of mortality from any cause, and incidence of cardiovascular disease and type 2 diabetes, as well as positive mental health and well-being. The largest potential for health gains likely to come from increasing participation amongst those who do not currently cycle regularly, rather than encouraging those who already cycle regularly to cycle more. Replacing car journeys with cycling can lead to reductions in air pollution emissions and lower pollutant exposure to the general population. Important gaps and uncertainties in the existing evidence base include: the extent to which the health benefits associated with cycling participation are fully causal due to the observational nature of much of the existing evidence base; the real-world economic cost-benefits of pragmatic interventions to increase cycling participation; and the most effective (combination of) approaches to increase cycling participation. To address these uncertainties, large-scale, long-term randomised controlled trials are needed to: evaluate the effectiveness, and cost-effectiveness, of (combinations of) intervention approaches to induce sustained long-term increases in cycling participation in terms of increases in numbers of people cycling regularly and number of cycling journeys undertaken, across a range of population demographic groups; establish the effects of such interventions on relevant outcomes related to health and wellbeing, economic productivity and wider societal impacts; and provide more robust quantification of potential harms of increasing cycling participation, such as collision risks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The nature of the Cycle Nation Project meant that the funders, British Cycling and HSBC UK, were intimately involved as representatives in this review. All analysis was performed by the authors without input from British Cycling or HSBC UK., (© 2023 Logan, Somers, Baker, Connell, Gray, Kelly, McIntosh, Welsh, Gray and Gill.)

Owing to their widespread properties, nitridophosphates are of high interest in current research. Explorative high-pressure high-temperature investigations yielded various compounds with stoichiometry MP 2 N 4 (M=Be, Ca, Sr, Ba, Mn, Cd), which are discussed as ultra-hard or luminescent materials, when doped with Eu 2+ . Herein, we report the first germanium nitridophosphate, GeP 2 N 4 , synthesized from Ge 3 N 4 and P 3 N 5 at 6 GPa and 800 °C. The structure was determined by single-crystal X-ray diffraction and further characterized by energy-dispersive X-ray spectroscopy, density functional theory calculations, IR and NMR spectroscopy. The highly condensed network of PN 4 -tetrahedra shows a strong structural divergence to other MP 2 N 4 compounds, which is attributed to the stereochemical influence of the lone pair of Ge 2+ . Thus, the formal exchange of alkaline earth cations with Ge 2+ may open access to various compounds with literature-known stoichiometry, however, new structures and properties., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Alzheimer's disease CSF biomarkers 42 amino acid long amyloid-β peptide (Aβ1-42), total tau protein (T-tau), and tau protein phosphorylated at threonine 181 (P-tau181) are considered surrogate biomarkers of Alzheimer's disease pathology, and significantly improve diagnostic accuracy. Their ability to reflect neuropathological changes later in the disease course is not well characterized. This study aimed to assess the potential of CSF biomarkers measured in mid to late stage Alzheimer's disease to reflect post-mortem neuropathological changes. Individuals were selected from two autopsy cohorts of Alzheimer's disease patients in Antwerp and Amsterdam. Neuropathological diagnosis was performed according to the updated consensus National Institute on Aging-Alzheimer's Association guidelines, which includes quantification of amyloid-β plaque, neurofibrillary tangle, and neuritic plaque load. CSF samples were analysed for Aβ1-42, T-tau, and P-tau181 by ELISA. One hundred and fourteen cases of pure definite Alzheimer's disease were included in the study (mean age 74 years, disease duration 6 years at CSF sampling, 50% females). Median interval between CSF sampling and death was 1 year. We found no association between Aβ1-42 and Alzheimer's disease neuropathological change profile. In contrast, an association of P-tau181 and T-tau with Alzheimer's disease neuropathological change profile was observed. P-tau181 was associated with all three individual Montine scores, and the associations became stronger and more significant as the interval between lumbar puncture and death increased. T-tau was also associated with all three Montine scores, but in individuals with longer intervals from lumbar puncture to death only. Stratification of the cohort according to APOE ε4 carrier status revealed that the associations applied mostly to APOE ε4 non-carriers. Our data suggest that similar to what has been reported for Aβ1-42, plateau levels of P-tau181 and T-tau are reached during the disease course, albeit at later disease stages, reducing the potential of tau biomarkers to monitor Alzheimer's disease pathology as the disease progresses. As a consequence, CSF biomarkers, which are performant for clinical diagnosis of early Alzheimer's disease, may not be well suited for staging or monitoring Alzheimer's disease pathology as it progresses through later stages., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The Cycle Nation Project (CNP) aimed to develop, test the feasibility of and optimize a multi-component individual-/social-level workplace-based intervention to increase cycling among office staff at a multinational bank (HSBC UK). To do this, we first explored barriers to cycling in a nationally-representative survey of UK adults, then undertook focus groups with bank employees to understand any context-specific barriers and ways in which these might be overcome. These activities led to identification of 10 individual-level, two social-level, and five organizational-level modifiable factors, which were mapped to candidate intervention components previously identified in a scoping review of cycling initiatives. Interviews with HSBC UK managers then explored the practicality of implementing the candidate intervention components in bank offices. The resultant pilot CNP intervention included 32 core components across six intervention functions (education, persuasion, incentivisation, training, environmental restructuring, enablement). Participants received a loan bike for 12-weeks (or their own bike serviced), and a 9-week cycle training course (condensed to 6 weeks for those already confident in basic cycling skills), including interactive information sharing activities, behavior change techniques (e.g., weekly goal setting), bike maintenance training, practical off-road cycling skill games and on-road group rides. Sessions were delivered by trained bank staff members who were experienced cyclists. The CNP pilot intervention was delivered across three sites with 68 participants. It was completed in two sites (the third site was stopped due to COVID-19) and was feasible and acceptable to both women and men and across different ethnicities. In addition, the CNP intervention was successful (at least in the short term) in increasing cycling by 3 rides/week on average, and improving perceptions of safety, vitality, confidence, and motivation to cycle. Following minor modifications, the long-term effectiveness and cost-effectiveness of the CNP intervention should be tested in a full-scale randomized controlled trial., Competing Interests: The nature of the co-design of the Cycle Nation Project intervention meant that the funders, British Cycling and HSBC UK, were intimately involved in the design and delivery of the intervention, and representatives from both organizations are authors on the paper. All data analysis was performed by researchers at the University of Glasgow without input from British Cycling or HSBC UK. Authors SB and JP were employed by British Cycling, and authors SR and LH are employees of HSBC UK. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Connell, Logan, Somers, Baker, Broadfield, Bunn, Harper, Kelly, McIntosh, Pell, Puttnam, Robson, Gill and Gray.)

Purpose: To assess whether saphenous somatosensory-evoked potentials (saphSSEP) monitoring may provide predictive information of femoral nerve health during prone lateral interbody fusion (LIF) procedures., Methods: Intraoperative details were captured prospectively in consecutive prone LIF surgeries at a single institution. Triggered electromyography was used during the approach; saphSSEP was monitored throughout using a novel system that enables acquisition of difficult signals and real-time actionable feedback facilitating intraoperative intervention. Postoperative neural function was correlated with intraoperative findings., Results: Fifty-nine patients (58% female, mean age 64, mean BMI 32) underwent LIF at 95 total levels, inclusive of L4-5 in 76%, fixated via percutaneous pedicle screws (81%) or lateral plate, with direct decompression in 39%. Total operative time averaged 149 min. Psoas retraction time averaged 16 min/level. Baseline SSEPs were unreliable in 3 due to comorbidities in 2 and anesthesia in 1; one of those resulted in transient quadriceps weakness, fully recovered at 6 weeks. In 25/56, no saphSSEP changes occurred, and none had postoperative femoral nerve deficits. In 24/31 with saphSSEP changes, responses recovered intraoperatively following intervention, with normal postoperative function in all but one with delayed quadriceps weakness, improved at 4 months and recovered at 9 months, and a second with transient isolated anterior thigh numbness. In the remaining 7/31, saphSSEP changes persisted to close, and resulted in 2 transient isolated anterior thigh numbness and 2 combined sensory and motor femoral nerve deficits, both resolved at between 4 and 8 months., Conclusions: SaphSSEP was reliably monitored in most cases and provided actionable feedback that was highly predictive of neurological events during LIF., Level of Evidence: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We aimed to evaluate the specificity of neurogranin (Ng) for Alzheimer's disease (AD) in a dementia cohort. Cerebrospinal fluid (CSF) Ng was measured (ELISA) in two independent cohorts: (1) clinical (n = 116; age 72±11 years): AD, non-AD (+high T-tau), and controls; and (2) autopsy-confirmed (n = 97; age 71±11 years): AD and non-AD, and 50 controls (age 60±6 years). In 16 autopsy-confirmed AD and 8 control subjects, Ng was measured in tissue (BA6+BA22). Ng was compared across diagnostic groups or neuropathological staging using multilinear regression models. Median[IQR] Ng concentrations were elevated in AD (414[315-499]pg/mL) and non-AD (464[319-699]pg/mL) compared to controls (260[193-306]pg/mL), but highest in AD-high-T-tau (874[716, 1148] pg/mL) and Creutzfeldt-Jakob disease (CJD; 828[703-1373]pg/mL) in cohort 1 (p < 0.01), but not in cohort 2: AD: 358[249-470]pg/mL; non-AD:245[137-416]pg/mL; controls: 259[193-370]pg/mL. Ng and tau biomarkers strongly correlated (r = 0.4-0.9, p < 0.05), except in CJD. CSF Ng concentrations were not associated with neuropathological AD hallmarks, nor with tissue Ng concentrations. CSF Ng is a general biomarker for synaptic degeneration, strongly correlating with CSF tau, but without added value for AD differential diagnosis., (Copyright © 2021. Published by Elsevier Inc.)

Background: Improving the academic achievement of youth in the United States is an area of interest and a critical indicator of the future success of the youth. The purpose of this study was to examine the impact of a comprehensive school physical activity and healthy eating program on 5th-grade students' academic achievement, specifically reading and math., Methods: Overall, 628 (intervention: 377, 54% girls; comparison: 251, 49% girls) 5th-grade children participated across the 6 schools in a year-long comprehensive health intervention, completing curriculum-based academic achievement measures at 2 time-points., Results: Results showed that even after controlling for class clustering, age, sex, race, and T1 reading and math variables, students' T2 reading and math achievement were significantly higher in the intervention group than the comparison group., Conclusions: Comprehensive health programming can enhance the health and academic achievement of youth., (© 2021, American School Health Association.)

Background. Responding to rising oncology therapy costs, multiple value frameworks are emerging. However, input from economists in their design and conceptualization has been limited, and no existing framework has been developed using preference weightings as legitimate indicators of value. This article outlines use of the nominal group technique to identify valued treatment attributes (such as treatment inconvenience) and contextual considerations (such as current life expectancy) to inform the design of a discrete choice experiment to develop a preference weighted value framework for future decision makers. Methods. Three focus groups were conducted in 2017 with cancer patients, oncology physicians, and nurses. Using the nominal group technique, participants identified and prioritized cancer therapy treatment and delivery attributes as well as contextual issues considered when choosing treatment options. Results. Focus groups with patients ( n = 8), physicians ( n = 6), and nurses ( n = 10) identified 30 treatment attributes and contextual considerations. Therapy health gains was the first priority across all groups. Treatment burden/inconvenience to patients and their families and quality of evidence were prioritized treatment attributes alongside preferences for resource use and cost (to patients and society) attributes. The groups also demonstrated that contextual considerations when choosing treatment varied across the stakeholders. Patients prioritized existence of alternative treatments and oncologist/center reputation while nurses focused on administration harms, communication, and treatment innovation. The physicians did not prioritize any contextual issues in their top rankings. Conclusions. The study demonstrates that beyond health gains, there are treatment attributes and contextual considerations that are highly prioritized across stakeholder groups. These represent important candidates for inclusion in a discrete choice experiment seeking to provide weighted preferences for a value framework for oncology treatment that goes beyond health outcomes., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The following authors are employed by the sponsor: Prof Briggs, Dr Susan Chimonas, Anna Kaltenboeck, and Dr Peter Bach.

Background: Changing population demographics and technology developments have resulted in growing interest in the potential of consumer-facing digital health. In the United Kingdom, a £37 million (US $49 million) national digital health program delivering assisted living lifestyles at scale (dallas) aimed to deploy such technologies at scale. However, little is known about how consumers value such digital health opportunities., Objective: This study explored consumers' perspectives on the potential value of digital health technologies, particularly mobile health (mHealth), to promote well-being by examining their willingness-to-pay (WTP) for such health solutions., Methods: A contingent valuation study involving a UK-wide survey that asked participants to report open-ended absolute and marginal WTP or willingness-to-accept for the gain or loss of a hypothetical mHealth app, Healthy Connections., Results: A UK-representative cohort (n=1697) and a dallas-like (representative of dallas intervention communities) cohort (n=305) were surveyed. Positive absolute and marginal WTP valuations of the app were identified across both cohorts (absolute WTP: UK-representative cohort £196 or US $258 and dallas-like cohort £162 or US $214; marginal WTP: UK-representative cohort £160 or US $211 and dallas-like cohort £151 or US $199). Among both cohorts, there was a high prevalence of zeros for both the absolute WTP (UK-representative cohort: 467/1697, 27.52% and dallas-like cohort: 95/305, 31.15%) and marginal WTP (UK-representative cohort: 487/1697, 28.70% and dallas-like cohort: 99/305, 32.5%). In both cohorts, better general health, previous amount spent on health apps (UK-representative cohort 0.64, 95% CI 0.27 to 1.01; dallas-like cohort: 1.27, 95% CI 0.32 to 2.23), and age had a significant (P>.00) association with WTP (UK-representative cohort: -0.1, 95% CI -0.02 to -0.01; dallas-like cohort: -0.02, 95% CI -0.03 to -0.01), with younger participants willing to pay more for the app. In the UK-representative cohort, as expected, higher WTP was positively associated with income up to £30,000 or US $39,642 (0.21, 95% CI 0.14 to 0.4) and increased spending on existing phone and internet services (0.52, 95% CI 0.30 to 0.74). The amount spent on existing health apps was shown to be a positive indicator of WTP across cohorts, although the effect was marginal (UK-representative cohort 0.01, 95% CI 0.01 to 0.01; dallas-like cohort 0.01, 95% CI 0.01 to 0.02)., Conclusions: This study demonstrates that consumers value mHealth solutions that promote well-being, social connectivity, and health care control, but it is not universally embraced. For mHealth to achieve its potential, apps need to be tailored to user accessibility and health needs, and more understanding of what hinders frequent users of digital technologies and those with long-term conditions is required. This novel application of WTP in a digital health context demonstrates an economic argument for investing in upskilling the population to promote access and expedite uptake and utilization of such digital health and well-being apps., (©Camilla Somers, Eleanor Grieve, Marilyn Lennon, Matt-Mouley Bouamrane, Frances S Mair, Emma McIntosh. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 17.01.2019.)

Disease-modifying treatment trials are increasingly advanced to the prodromal or preclinical phase of Alzheimer's disease (AD), and inclusion criteria are based on biomarkers rather than clinical symptoms. Therefore, it is of great interest to determine which biomarkers should be combined to accurately predict conversion from mild cognitive impairment (MCI) to AD dementia. However, up to date, only few studies performed a complete A/T/N subject characterization using each of the CSF and imaging markers, or they only investigated long-term (≥ 2 years) prognosis. This study aimed to investigate the association between cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), amyloid- and 18 F-FDG positron emission tomography (PET) measures at baseline, in relation to cognitive changes and conversion to AD dementia over a short-term (12-month) period. We included 13 healthy controls, 49 MCI and 16 AD dementia patients with a clinical-based diagnosis and a complete A/T/N characterization at baseline. Global cortical amyloid-β (Aβ) burden was quantified using the 18 F-AV45 standardized uptake value ratio (SUVR) with two different reference regions (cerebellar grey and subcortical white matter), whereas metabolism was assessed based on 18 F-FDG SUVR. CSF measures included Aβ 1-42 , Aβ 1-40 , T-tau, P-tau 181 , and their ratios, and MRI markers included hippocampal volumes (HV), white matter hyperintensities, and cortical grey matter volumes. Cognitive functioning was measured by MMSE and RBANS index scores. All statistical analyses were corrected for age, sex, education, and APOE ε4 genotype. As a result, faster cognitive decline was most strongly associated with hypometabolism (posterior cingulate) and smaller hippocampal volume (e.g., Δstory recall: β = +0.43 [p < 0.001] and + 0.37 [p = 0.005], resp.) at baseline. In addition, faster cognitive decline was significantly associated with higher baseline Aβ burden only if SUVR was referenced to the subcortical white matter (e.g., Δstory recall: β = -0.28 [p = 0.020]). Patients with MCI converted to AD dementia at an annual rate of 31%, which could be best predicted by combining neuropsychological testing (visuospatial construction skills) with either MRI-based HV or 18 F-FDG-PET. Combining all three markers resulted in 96% specificity and 92% sensitivity. Neither amyloid-PET nor CSF biomarkers could discriminate short-term converters from non-converters., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Despite decades of research on the optimization of the diagnosis of Alzheimer's disease (AD), its biomarker-based diagnosis is being hampered by the lack of comparability of raw biomarker data. In order to overcome this limitation, the Erlangen Score (ES), among other approaches, was set up as a diagnostic-relevant interpretation algorithm., Objective: To validate the ES algorithm in a cohort of neuropathologically confirmed cases with AD (n = 106) and non-AD dementia (n = 57)., Methods: Cerebrospinal fluid (CSF) biomarker concentrations of Aβ1-42, T-tau, and P-tau181 were measured with commercially available single analyte ELISA kits. Based on these biomarkers, ES was calculated as previously reported., Results: This algorithm proved to categorize AD in different degrees of likelihood, ranging from neurochemically "normal", "improbably having AD", "possibly having AD", to "probably having AD", with a diagnostic accuracy of 74% using the neuropathology as a reference., Conclusion: The ability of the ES to overcome the high variability of raw CSF biomarker data may provide a useful diagnostic tool for comparing neurochemical diagnoses between different labs or methods used.

Background: Beginning in the elementary school years, there are differences among children on how they perceive their competence in physical activity (PA). Children's competence perceptions may influence their affective reactions to PA. A crucial question is how to motivate children who hold low competence perceptions to enhance their enjoyment and PA involvement. Because parents play critical roles in children's development and socialization, social support from parents can be an important factor to complement teachers' effort to enhance children's enjoyment and PA involvement. In this research we identified the associations among children's beliefs about parental social support, perceived competence, and enjoyment in school PA., Methods: Three hundred and twenty children (9-11 years old) participated in a two-wave study. At the first wave, children completed questionnaires measuring their beliefs about parental social support, perceived competence, and enjoyment in school PA; they reported their enjoyment again 8 months later at the second wave., Results: Both concurrent and longitudinal analyses revealed that beliefs about parental social support were important factors associated with children's enjoyment in school PA, especially among girls with low competence perceptions., Conclusion: Family socialization factors should be taken into consideration. The efficacy of individual and community-level strategies should be included and evaluated when designing effective intervention strategies that enhance children's PA in school.

Increased brain uptake of 18 F-AV45 visualized by PET is a key biomarker for Alzheimer disease (AD). The SUV ratio (SUVR) is widely used for quantification, but is subject to variability based on choice of reference region and changes in cerebral blood flow. Here we validate the SUVR method against the gold standard volume of distribution (V T ) to assess cross-sectional differences in plaque load. Methods: Dynamic 60-min 18 F-AV45 (291 ± 67 MBq) and 1-min 15 O-H 2 O (370 MBq) scans were obtained in 35 age-matched elderly subjects, including 10 probable AD, 15 amnestic mild cognitive impairment (aMCI), and 10 cognitively healthy controls (HCs). 18 F-AV45 V T was determined from 2-tissue-compartment modeling using a metabolite-corrected plasma input function. Static SUVR was calculated at 50-60 min after injection, using either cerebellar gray matter (SUVR CB ) or whole subcortical white matter (SUVR WM ) as the reference. Additionally, whole cerebellum, pons, centrum semiovale, and a composite region were examined as alternative references. Blood flow was quantified by 15 O-H 2 O SUV. Data are presented as mean ± SEM. Results: There was rapid metabolization of 18 F-AV45, with only 35% of unchanged parent remaining at 10 min. Compared with V T , differences in cortical Aβ load between aMCI and AD were overestimated by SUVR WM (+4% ± 2%) and underestimated by SUVR CB (-10% ± 2%). V T correlated better with SUVR WM (Pearson r: from 0.63 for posterior cingulate to 0.89 for precuneus, P < 0.0001) than with SUVR CB (Pearson r: from 0.51 for temporal lobe [ P = 0.002] to 0.82 for precuneus [ P < 0.0001]) in all tested regions. Correlation results for the alternative references were in between those for CB and WM. 15 O-H 2 O data showed that blood flow was decreased in AD compared with aMCI in cortical regions (-5% ± 1%) and in the reference regions (CB, -9% ± 8%; WM, -8% ± 8%). Conclusion: Increased brain uptake of 18 F-AV45 assessed by the simplified static SUVR protocol does not truly reflect Aβ load. However, SUVR WM is better correlated with V T and more closely reflects V T differences between aMCI and AD than SUVR CB ., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: The Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers Aβ 1-42 , t-tau, and p-tau 181 overlap with other diseases. New tau modifications or epitopes, such as the non-phosphorylated tau fraction (p-tau rel ), may improve differential dementia diagnosis. The goal of this study is to investigate if p-tau rel can improve the diagnostic performance of the AD CSF biomarker panel for differential dementia diagnosis., Methods: The study population consisted of 45 AD, 45 frontotemporal lobar degeneration (FTLD), 45 dementia with Lewy bodies (DLB), and 21 Creutzfeldt-Jakob disease (CJD) patients, and 20 cognitively healthy controls. A substantial subset of the patients was pathology-confirmed. CSF levels of Aβ 1-42 , t-tau, p-tau 181 , and p-tau rel were determined with commercially available single-analyte enzyme-linked immunosorbent assay (ELISA) kits. Diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analyses, and area under the curve (AUC) values were compared using DeLong tests., Results: The diagnostic performance of single markers as well as biomarker ratios was determined for each pairwise comparison of different dementia groups and controls. The addition of p-tau rel to the AD biomarker panel decreased its diagnostic performance when discriminating non-AD, FTLD, and DLB from AD. As a single marker, p-tau rel increased the diagnostic performance for CJD. No significant difference was found in AUC values with the addition of p-tau rel when differentiating between AD or non-AD dementias and controls., Conclusions: The addition of p-tau rel to the AD CSF biomarker panel failed to improve differentiation between AD and non-AD dementias.

Although the core cerebrospinal fluid Alzheimer's disease (AD) biomarkers amyloid-β (Aβ 1-42 ) and tau show a high diagnostic accuracy, there are still limitations due to overlap in the biomarker levels with other neurodegenerative and dementia disorders. During Aβ 1-42 production and clearance in the brain, several other Aβ peptides and amyloid precursor protein fragments are formed that could potentially serve as biomarkers for this ongoing disease process. Therefore, this review will present the current status of the findings for amyloid precursor protein and Aβ peptide isoforms in AD and clinically related disorders. In conclusion, adding new Aβ isoforms to the AD biomarker panel may improve early differential diagnostic accuracy and increase the cerebrospinal fluid biomarker concordance with AD neuropathological findings in the brain.

Background: Evidence suggests that the concordance between amyloid-PET and cerebrospinal fluid (CSF) amyloid-β (Aβ) increases when the CSF Aβ1-42/Aβ1-40 ratio is used as compared to CSF Aβ1-42 levels alone., Objective: In order to test this hypothesis, we set up a prospective longitudinal study comparing the concordance between different amyloid biomarkers for Alzheimer's disease (AD) in a clinical setting., Methods: Seventy-eight subjects (AD dementia (n = 17), mild cognitive impairment (MCI, n = 48), and cognitively healthy controls (n = 13)) underwent a [18F]Florbetapir ([18F]AV45) PET scan, [18F]FDG PET scan, MRI scan, and an extensive neuropsychological examination. In a large subset (n = 67), a lumbar puncture was performed and AD biomarkers were analyzed (Aβ1-42, Aβ1-40, T-tau, P-tau181)., Results: We detected an increased concordance in the visual and quantitative (standardized uptake value ratio (SUVR) and total volume of distribution (VT)) [18F]AV45 PET measures when the CSF Aβ1-42/Aβ1-40 was applied compared to Aβ1-42 alone. CSF biomarkers were stronger associated to [18F]AV45 PET for SUVR values when considering the total brain white matter as reference region instead of cerebellar grey matterConclusions:The concordance between CSF Aβ and [18F]AV45 PET increases when the CSF Aβ1-42/Aβ1-40 ratio is applied. This finding is of most importance for the biomarker-based diagnosis of AD as well as for selection of subjects for clinical trials with potential disease-modifying therapies for AD.

During the past ten years, over 5,000 cerebrospinal fluid (CSF) samples were analyzed at the Reference Center for Biological Markers of Dementia (BIODEM), UAntwerp, for core Alzheimer's disease (AD) CSF biomarkers: amyloid-β peptide of 42 amino acids (Aβ1-42), total tau protein (T-tau), and tau phosphorylated at threonine 181 (P-tau181P). CSF biomarker analyses were performed using single-analyte ELISA kits. In-house validated cutoff values were applied: Aβ1-42 <638.5 pg/mL, T-tau >296.5 pg/mL, P-tau181P >56.5 pg/mL. A CSF biomarker profile was considered to be suggestive for AD if the CSF Aβ1-42 concentration was below the cutoff, in combination with T-tau and/or P-tau181P values above the cutoff (IWG2 criteria for AD). Biomarker analyses were requested for following clinical indications: 1) neurochemical confirmation of AD in case of clinical AD, 2) neurochemical confirmation of AD in case of doubt between AD and a non-AD dementia, 3) neurochemical diagnosis of prodromal AD in case of mild cognitive impairment, 4) neurochemical confirmation of AD in case of psychiatric symptoms (like depression, psychosis), or 5) other clinical indications. During these ten years, the number of yearly referred samples increased by 238% and clinical indications for referral showed a shift from neurochemical confirmation of AD in case of clinical AD to differential dementia diagnosis in case of doubt between AD and a non-AD dementia. Four percent of the patients also had a postmortem neuropathological examination. Together, these biomarker data were the basis for several research papers, and significantly contributed to the validation of these biomarkers in autopsy-confirmed subjects.

This study investigated a reciprocal effects model (REM) of children's body fat self-concept and physical self-concept, and objectively measured school physical activity at different intensities. Grade four students (N = 376; M age = 9.07, SD = .61; 55% boys) from the midwest region of the United States completed measures of physical self-concept and body fat self-concept, and wore accelerometers for three consecutive school days at the beginning and end of one school year. Findings from structural equation modeling analyses did not support reciprocal effects. However, children's body fat self-concept predicted future physical self-concept and moderate-to-vigorous physical activity (MVPA). Multigroup analyses explored the moderating role of weight status, sex, ethnicity, and sex*ethnicity within the REM. Findings supported invariance, suggesting that the observed relations were generalizable for these children across demographic groups. Links between body fat self-concept and future physical self-concept and MVPA highlight self-enhancing effects that can promote children's health and well-being.

Background: Q fever is rarely reported in children/adolescents. Although lower reporting rates are commonly attributed to milder disease and subsequent underdiagnosis in infected children/adolescents, pertinent evidence is scarce. We present data from a large, well-defined single-point source outbreak of Q fever to fill this gap., Methods: We compared (A) Q fever testing and notification rates in children/adolescents who were 0-19 years of age with those in adults 20+ years of age in October 2009; (B) serological attack rates of acute Q fever in children/adolescents with the rates in adults after on-source exposure on the outbreak farm's premises; (C) incidence of Q fever infection in children/adolescents with that in adults after off-source exposure in the municipality located closest to the farm., Results: (A) Children/adolescents represented 19.3% (59,404 of 307,348) of the study area population, 12.1% (149 of 1217) of all subjects tested in October 2009 and 4.3% (11 of 253) of notified laboratory-confirmed community cases. (B) Serological attack rate of acute Q fever in children with on-source exposure was 71% (12 of 17), similar to adults [68% (40 of 59)]. (C) Incidence of infection in children/adolescents after community (off-source) exposure was 4.5% (13 of 287) versus 11.0% (12 of 109) in adults (adjusted odds ratio: 0.36; 95% confidence interval: 0.16-0.84; P = 0.02). No children/adolescents reported clinical symptoms. Proportion of notified infections was significantly lower in children/adolescents (2.5%) than in adults (10.4%; risk ratio: 0.26; 95% confidence interval: 0.08-0.80, P = 0.02)., Conclusion: Notified Q fever was less frequent in children/adolescents than in adults. Although underrecognition contributed to this phenomenon, lower rates of infection in children after community exposure played an unexpected major role. On-source (presumed high-dose) exposure, by contrast, was associated with high serological and clinical attack rates not only in adults but also in children/adolescents. Our findings allow for improved age-specific clinical and public health risk assessment in Q fever outbreaks.

Pasture-based livestock systems are often associated with losses of reactive forms of nitrogen (N) to the environment. Research has focused on losses to air and water due to the health, economic and environmental impacts of reactive N. Di-nitrogen (N2) emissions are still poorly characterized, both in terms of the processes involved and their magnitude, due to financial and methodological constraints. Relatively few studies have focused on quantifying N2 losses in vivo and fewer still have examined the relative contribution of the different N2 emission processes, particularly in grazed pastures. We used a combination of a high (15)N isotopic enrichment of applied N with a high precision of determination of (15)N isotopic enrichment by isotope-ratio mass spectrometry to measure N2 emissions in the field. We report that 55.8 g N m(-2) (95%, CI 38 to 77 g m(-2)) was emitted as N2 by the process of co-denitrification in pastoral soils over 123 days following urine deposition (100 g N m(-2)), compared to only 1.1 g N m(-2) (0.4 to 2.8 g m(-2)) from denitrification. This study provides strong evidence for co-denitrification as a major N2 production pathway, which has significant implications for understanding the N budgets of pastoral ecosystems.

Background: Non-volitional sex (NVS) in young people continues to be a major public health problem with long-term negative health outcomes. For the first time, the prevalence of different types of NVS and associated factors are compared between young people with same-sex sexual activities and those who have not., Methods: We obtained data from 10,401 young women and men (aged 12 to 25 years) who participated in a population study on sexual health, the Netherlands. We calculated and compared the prevalence of six types of NVS between women who had sex with men (yWSM) or women (yWSW), and men who had sex with women (yMSW) or men (yMSM). In sexually experienced participants (n = 5986) logistic regression analyses were applied to assess associations with NVS by assault or penetration. Analyses were weighted to represent the Dutch population., Results: The prevalence of NVS ranged from 1% to 61%, depending on type. Prevalence was higher for young women (any: 40.6%) than men (any: 20.4%), and highest for yMSM and yWSW. Prevalence of NVS by assault or penetration was related to a range of socio-demographic, behavioral and social factors, which were largely similar regardless of sex or same-sex-experiences. The NVS perpetrators were in over 70% of cases known to the victim; 1 in 4 cases of NVS by penetration were accompanied by violence., Conclusion: A substantial proportion of young people in the Netherlands have experienced NVS. Medical professionals, educators and caregivers should integrate services to continue to address NVS by targeting young people's multifaceted risk profiles and evidenced based interventions for doing so are needed.

Critical windows are periods of developmental susceptibility when the phenotype of an embryonic, juvenile or adult animal may be vulnerable to environmental fluctuations. Temperature has pervasive effects on poikilotherm physiology, and embryos are especially vulnerable to temperature shifts. To identify critical windows, we incubated whitefish embryos at control temperatures of 2°C, 5°C, or 8°C, and shifted treatments among temperatures at the end of gastrulation or organogenesis. Heart rate (fH) and oxygen consumption ( [Formula: see text] ) were measured across embryonic development, and [Formula: see text] was measured in 1-day old hatchlings. Thermal shifts, up or down, from initial incubation temperatures caused persistent changes in fH and [Formula: see text] compared to control embryos measured at the same temperature (2°C, 5°C, or 8°C). Most prominently, when embryos were measured at organogenesis, shifting incubation temperature after gastrulation significantly lowered [Formula: see text] or fH. Incubation at 2°C or 5°C through gastrulation significantly lowered [Formula: see text] (42% decrease) and fH (20% decrease) at 8°C, incubation at 2°C significantly lowered [Formula: see text] (40% decrease) and fH (30% decrease) at 5°C, and incubation at 5°C and 8°C significantly lowered [Formula: see text] at 2°C (27% decrease). Through the latter half of development, [Formula: see text] and fH in embryos were not different from control values for thermally shifted treatments. However, in hatchlings measured at 2°C, [Formula: see text] was higher in groups incubated at 5°C or 8°C through organogenesis, compared to 2°C controls (43 or 65% increase, respectively). Collectively, these data suggest that embryonic development through organogenesis represents a critical window of embryonic and hatchling phenotypic plasticity. This study presents an experimental design that identified thermally sensitive periods for fish embryos., (Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.)

The effectiveness of chemical amendment of pig slurry to ameliorate phosphorus (P) losses in runoff is well studied, but research mainly has concentrated only on the runoff pathway. The aims of this study were to investigate changes to leachate nutrient losses, soil properties and greenhouse gas (GHG) emissions due to the chemical amendment of pig slurry spread at 19 kg total phosphorus (TP), 90 kg total nitrogen (TN), and 180 kg total carbon (TC) ha(-1). The amendments examined were: (1) commercial grade liquid alum (8% Al2O3) applied at a rate of 0.88:1 [Al:TP], (2) commercial-grade liquid ferric chloride (38% FeCl3) applied at a rate of 0.89:1 [Fe:TP] and (3) commercial-grade liquid poly-aluminium chloride (PAC) (10% Al2O3) applied at a rate of 0.72:1 [Al:TP]. Columns filled with sieved soil were incubated for 8 mo at 10 °C and were leached with 160 mL (19 mm) distilled water wk(-1). All amendments reduced the Morgan's phosphorus and water extractable P content of the soil to that of the soil-only treatment, indicating that they have the ability to reduce P loss in leachate following slurry application. There were no significant differences between treatments for nitrogen (N) or carbon (C) in leachate or soil, indicating no deleterious impact on reactive N emissions or soil C cycling. Chemical amendment posed no significant change to GHG emissions from pig slurry, and in the cases of alum and PAC, reduced cumulative N2O and CO2 losses. Chemical amendment of land applied pig slurry can reduce P in runoff without any negative impact on nutrient leaching and GHG emissions. Future work must be conducted to ascertain if more significant reductions in GHG emissions are possible with chemical amendments., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Hospital HIV care and public sexual health care (a Sexual Health Care Centre) services were integrated to provide sexual health counselling and sexually transmitted infections (STIs) testing and treatment (sexual health care) to larger numbers of HIV patients. Services, need and usage were assessed using a patient perspective, which is a key factor for the success of service integration., Methods: The study design was a one-group pre-test and post-test comparison of 447 HIV-infected heterosexual individuals and men who have sex with men (MSM) attending a hospital-based HIV centre serving the southern region of the Netherlands. The intervention offered comprehensive sexual health care using an integrated care approach. The main outcomes were intervention uptake, patients' pre-test care needs (n=254), and quality rating., Results: Pre intervention, 43% of the patients wanted to discuss sexual health (51% MSM; 30% heterosexuals). Of these patients, 12% to 35% reported regular coverage, and up to 25% never discussed sexual health topics at their HIV care visits. Of the patients, 24% used our intervention. Usage was higher among patients who previously expressed a need to discuss sexual health. Most patients who used the integrated services were new users of public health services. STIs were detected in 13% of MSM and in none of the heterosexuals. The quality of care was rated good., Conclusions: The HIV patients in our study generally considered sexual health important, but the regular counselling and testing at the HIV care visit was insufficient. The integration of public health and hospital services benefited both care sectors and their patients by addressing sexual health questions, detecting STIs, and conducting partner notification. Successful sexual health care uptake requires increased awareness among patients about their care options as well as a cultural shift among care providers.

Materials and Methods: To minimize delays in time to reperfusion in an urban-suburban North Carolina County, Guilford County Emergency Medical Services (EMS) and Moses Cone Hospital, Greensboro, NC, have collaborated to use the acquisition of 12-lead electrocardiographs and their paramedic interpretation to initiate the catheterization laboratory team and cardiologist; independent of over read by a physician. The study population of 91 patients was divided into the catheterization laboratory activation by EMS and catheterization laboratory activation by the emergency department physician (ED-MD) groups, and also by EMS and self-transported groups., Results: The EMS group had shorter median time intervals from hospital door to percutaneous coronary intervention (PCI) with balloon inflation than those patients who self-transported to the hospital. Also, patients who were treated during the EMS activation of the catheterization laboratory phase had shorter median hospital door to PCI times than those who were treated during ED-MD activation of the catheterization laboratory., Conclusion: The time from hospital arrival to PCI with balloon inflation was significantly shorter during the period in which EMS activated the catheterization laboratory than during the period the laboratory was activated by hospital staff. Thus, paramedics with quality electrocardiogram interpretation training and education can identify patients with acute ST-elevation myocardial infarction and properly activate the catheterization laboratory., (Copyright © 2011. Published by Elsevier Inc.)

Several studies have described a clear association between respiratory syncytial virus (RSV) lower respiratory tract infection in infancy and the subsequent development of persistent wheezing in children. Using the mouse model we demonstrated that RSV induces long-term airway disease characterized by chronic airway inflammation and airway hyperreactivity (AHR). The RSV murine model offers great advantages to study the immunopathogenesis of RSV-induced long-term airway disease. Mice can be challenged with aerosolized methylcholine to determine the presence of AHR. We can apply the reverse transcription-polymerase chain reaction assay (RT-PCR) to detect RSV RNA in the respiratory tract and we can perform lung gene expression analysis to further characterize the chronic changes induced by RSV infection. Compared with sham-inoculated controls, RSV-infected mice developed chronic airway disease characterized by AHR and persistent airway inflammation. Forty-two days after RSV infection, a time point when RSV could no longer be isolated, RT-PCR demonstrated, quite unexpectedly, the presence of RSV RNA in the lower respiratory tract of mice. The presence of genomic RNA persisted for months after inoculation. Furthermore, preliminary studies also demonstrated that on day 42 there were a number of genes differentially expressed in RSV-infected mice compared with controls. RSV-infected mice with persistent AHR exhibited presence of abnormal chronic inflammatory changes, altered gene expression profiles, and persistence of RSV RNA, which may contribute to long-term airway disease induced by RSV. Future studies are needed to define the significance of persistent RSV RNA in the mouse model, and its potential role in the pathogenesis of RSV-induced persistent wheezing in children.

Infection by RNA viruses is detected by the host through Toll-like receptors or RIG-I-like receptors. Toll-like receptors and RIG-I-like receptors signal through the adaptors MyD88 and MAVS, respectively, to induce type I IFNs (IFN-I) and other antiviral molecules, which are thought to be essential for activating the adaptive immune system. We investigated the role of these adaptors in innate and adaptive immune responses against respiratory syncytial virus (RSV), a common human pathogen. Deletion of Mavs abolished the induction of IFN-I and other proinflammatory cytokines by RSV. Genome-wide expression profiling in the lung showed that the vast majority of RSV-induced genes depended on MAVS. Although Myd88 deficiency did not affect most RSV-induced genes, mice lacking both adaptors harbored a higher and more prolonged viral load and exhibited more severe pulmonary disease than those lacking either adaptor alone. Surprisingly, Myd88(-/-)Mavs(-/-) mice were able to activate a subset of pulmonary dendritic cells that traffic to the draining lymph node in response to RSV. These mice subsequently mounted a normal cytotoxic T-lymphocyte response and demonstrated delayed but effective viral clearance. These results provide an example of a normal and effective adaptive immune response in the absence of innate immunity mediated by MAVS and MyD88.

To define the prevalence and correlates of grief-related symptoms among long-term care staff who care for patients near the end of life, a cross-sectional survey was conducted at six Program of All-inclusive Care for the Elderly (PACE) organizations that provide long-term care in the home and in institutions. All clinical and non-clinical program staff were surveyed to examine the prevalence of 20 grief-related symptoms and assess current sources of bereavement support, as well as willingness to use additional sources of support. Surveys were completed by 203/236 staff (86%), who described a wide variety of symptoms they attributed to the death of one of their patients in the past month. Most staff (147/203; 72%) reported at least one symptom. Staff with more symptoms had experienced more patient deaths in the past month (Spearman rho = 0.20, P = 0.007), had worked for a longer time at a PACE organization (Spearman rho = 0.16, P = 0.031), and reported a closer and longer relationship with the last patient who died (Spearman rho = 0.32, P < 0.001; rho = 0.24, P = 0.001). Although staff identified several informal sources of bereavement support (mean 2.3 sources, range 0-6), almost all (n = 194; 96%) said they would use additional support services if they were offered. These community-based long-term care staff experience a variety of symptoms attributable to the deaths of their patients, and would welcome additional sources of bereavement support.

Recent studies have shown that expanded-simple-tandem-repeat (ESTR) DNA loci are efficient genetic markers for detecting radiation-induced germline mutations in mice. Dose responses following irradiation, however, have only been characterized in a small number of inbred mouse strains, and no studies have applied ESTRs to examine potential modifiers of radiation risk, such as adaptive response. We gamma-irradiated groups of male out-bred Swiss-Webster mice with single acute doses of 0.5 and 1.0 Gy, and compared germline mutation rates at ESTR loci to a sham-irradiated control. To test for evidence of adaptive response we treated a third group with a total dose of 1.1 Gy that was fractionated into a 0.1 Gy adapting dose, followed by a challenge dose of 1.0 Gy 24h later. Paternal mutation rates were significantly elevated above the control in the 0.5 Gy (2.8-fold) and 1.0 Gy (3.0-fold) groups, but were similar to each other despite the difference in radiation dose. The doubling dose for paternal mutation induction was 0.26 Gy (95% CI = 0.14-0.51 Gy). Males adapted with a 0.1 Gy dose prior to a 1.0 Gy challenge dose had mutation rates that were not significantly elevated above the control, and were 43% reduced compared to those receiving single doses. We conclude that pre-meiotic male germ cells in out-bred Swiss-Webster mice are sensitive to ESTR mutations induced by acute doses of ionizing radiation, but mutation induction may become saturated at a lower dose than in some strains of inbred mice. Reduced mutation rates in the adapted group provide intriguing evidence for suppression of ESTR mutations in the male germline through adaptive response. Repetitive DNA markers may be useful tools for exploration of biological factors affecting the probability of heritable mutations caused by low-dose ionizing radiation exposure. The biological significance of ESTR mutations in terms of radiation risk assessment, however, is still undetermined.

Extract: In a recent study we showed that the particulate fraction of air pollution was capable of increasing the rate at which DNA changes were passed to the next generation (germline mutations) in mice. Here we briefly describe the research that brought us to this experiment, followed by a description of the recent study and its implications. Herring gulls (Larus argentatus) are fish-eating water birds that breed throughout the Laurentian Great Lakes and in many other parts of the Northern Hemisphere. In the early to mid 1990's, these birds were used as a sentinel wildlife species in our studies of germline mutations as a function of distance from integrated steel mills. The assay used involved comparison of the DNA profiles (minisatellite DNA -- non-coding sequences) of gull offspring with those of their parents, and identification of novel bands, or mutations, in the DNA profiles of offspring.

In an effort to reduce teen pregnancy, schools are purchasing a program called "Baby Think It Over," a computerized infant simulator intended to provide a realistic infant care experience. However, little empirical, especially experimental, program effectiveness data exist. This study determined if the program changed participants' attitudes toward parenting, as well as sexual and contraceptive behaviors linked to avoidance of teen pregnancy. Development of measurement tools was a part of the purpose. The study also asked teen-agers, through narrative questions, about their conscious perceptions of the baby's utility and impact. Participants included experimental (n = 151) and control (n = 62) groups of primarily White, middle class, suburban high school' students (mean age = 16.2). The quasi-experimental portion of the study failed to reveal a statistically significant effect. Narrative data revealed several positive and notable program effects.

Platypnea-orthodeoxia syndrome is a rare entity most often related to an interatrial right-to-left shunt. We report the case of a patient who developed platypnoea-orthodeoxia shortly after a blunt chest wall trauma. Definite diagnosis was obtained with transoesophageal echocardiography using contrast in upright and recumbent position. A Medline search did not reveal any other case report of the syndrome after chest wall injury.

Fibroblasts have cell surface sites that mediate the assembly of fibronectin (Fn) into the extracellular matrix. Treatment of fibroblasts with kinase inhibitors (ML-7, H7, HA1004, calphostin C, and staurosporine) resulted in the rapid decrease in the binding of 125I-labeled plasma Fn and iodinated amino-terminal fragments of Fn. The dose responses of the four inhibitors suggest that the target kinase is protein kinase C (PKC) rather than the cyclic AMP- or cyclic GMP-dependent kinases. Three different fibroblastic cells were similarly affected. The inhibition was rapid and reversible and could not be overcome by increasing concentrations of Fn. Treatment of fibroblasts with phorbol esters and other agents that activate PKC resulted in increased amounts of 125I-labeled Fn binding to the cell surface. These results imply that Fn matrix assembly is modulated by PKC-mediated phosphorylation.

The University of Massachusetts at Lowell Work Environment Department, working jointly with four New England coalitions on occupational safety and health (COSH) groups, has developed and is delivering participatory and learner-centered health and safety training for hazardous waste site workers and emergency responders throughout New England. This consortium has created a technical curriculum for hazardous waste workers accessible to the nonspecialist and which, more importantly, draws upon workers' own experience and knowledge as a source of information, education, and experiential resources. In this article, we examine the goals of the consortium, the applicability of the training method, its successes and failures, and the wider implications such pedagogical techniques have for effective and empowering health and safety training. We conclude that such a teaching technique is a successful means of providing technical knowledge and skills in a positive and rewarding atmosphere. We also conclude, however, that the extent to which this form of education is empowering, as is claimed by many of its proponents, is less clear-cut.

Ovoperoxidase, the enzyme that hardens the sea urchin fertilization envelope, is inserted into the assembling extracellular matrix through the action of an intermediary protein, proteoliaisin (PLN). The domain structure of PLN, a large, rod-shaped protein that binds to ovoperoxidase and the vitelline layer, was examined by limited proteolytic cleavage. Purified proteolytic fragments of PLN were tested for their ability to bind ovoperoxidase, inhibit the binding of 125I-PLN to the vitelline layer, or act as substrates for the hardening reaction. Based on these results, the vitelline layer-binding domain can be placed near the amino terminus, followed by the binding site for ovoperoxidase; the distal two-thirds of the protein contain sites for ovoperoxidase-catalyzed dityrosine formation. The pentapeptide GRGDS (but not RGD) inhibited PLN-vitelline layer binding half-maximally at 0.2 mM. Moreover, PLN promoted adhesion of bovine aortic endothelial cells to plastic dishes, a process inhibited by GRGDS. Thus PLN is a new member of the adhesive protein family, the function of which is to coordinate the morphogenesis of a specific, rapidly assembled extracellular matrix.

Recoveries of third stage Dicytocaulus viviparus larvae (L3) from Pilobolus species sporangia ranged from 23 per cent at 21 days to 3 per cent after 90 days for sporangia attached to polythene discs positioned on pasture. There was a continuous release of L3 for up to 16 days from sporangia which were placed under conditions simulating those occurring on pasture.