RESPOND – A patient-centred programme to prevent secondary falls in older people presenting to the emergency department with a fall: Protocol for a mixed methods programme evaluation.

Background Programme evaluations conducted alongside randomised controlled trials (RCTs) have potential to enhance understanding of trial outcomes. This paper describes a multi-level programme evaluation to be conducted alongside an RCT of a falls prevention programme (RESPOND). Objectives 1) To conduct a process evaluation in order to identify the degree of implementation fidelity and associated barriers and facilitators. 2) To evaluate the primary intended impact of the programme: participation in fall prevention strategies, and the factors influencing participation. 3) To identify the factors influencing RESPOND RCT outcomes: falls, fall injuries and ED re-presentations. Methods/ Design Five hundred and twenty eight community-dwelling adults aged 60–90 years presenting to two EDs with a fall will be recruited and randomly assigned to the intervention or standard care group. All RESPOND participants and RESPOND clinicians will be included in the evaluation. A mixed methods design will be used and a programme logic model will frame the evaluation. Data will be sourced from interviews, focus groups, questionnaires, clinician case notes, recruitment records, participant-completed calendars, hospital administrative datasets, and audio-recordings of intervention contacts. Quantitative data will be analysed via descriptive and inferential statistics and qualitative data will be interpreted using thematic analysis. Discussion The RESPOND programme evaluation will provide information about contextual and influencing factors related to the RCT outcomes. The results will assist researchers, clinicians, and policy makers to make decisions about future falls prevention interventions. Insights gained are likely to be transferable to preventive health programmes for a range of chronic conditions

Thirty Years of Cometary Spectroscopy from McDonald Observatory

We report on the results of a spectroscopic survey of 130 comets that was conducted at McDonald observatory from 1980 through 2008. Some of the comets were observed on only one night, while others were observed repeatedly. For 20 of these comets, no molecules were detected. For the remaining 110 comets, some emission from CN, OH, NH, C$_{3}$, C$_{2}$, CH, and NH$_{2}$ molecules were observed on at least one occasion. We converted the observed molecular column densities to production rates using a Haser (1957) model. We defined a restricted data set of comets that had at least 3 nights of observations. The restricted data set consists of 59 comets. We used ratios of production rates to study the trends in the data. We find two classes of comets: typical and carbon-chain depleted comets. Using a very strict definition of depleted comets, requiring C$_{2}$ \underline{and} C$_{3}$ to both be depleted, we find 9% of our restricted data set comets to be depleted. Using a more relaxed definition that requires only C$_{2}$ to be below a threshold (similar to other researchers), we find 25% of the comets are depleted. Two-thirds of the depleted comets are Jupiter Family comets, while one-third are Long Period comets. 37% of the Jupiter Family comets are depleted, while 18.5% of the Long Period comets are depleted. We compare our results with other studies and find good agreement.Comment: Accepted for Icarus; 15 figures, 9 tables (some multi-page and in landscape mode

Carbon isotope signatures from land snail shells: Implications for palaeovegetation reconstruction in the eastern Mediterranean

In this studywecompare carbon isotope values inmodern Helix melanostoma shell carbonate (d13Cshell) from the Gebel al-Akhdar region of Libya with carbon isotope values in H. melanostomabody tissue (d13Cbody), local vegetation (d13Cplant) and soil (d13Csoil). All vegetation in the study area followed the C3 photosynthetic pathway. However, the d13Cplant values of different species formed two distinct isotopic groups. This can be best explained by different water use efficiencies with arid adapted species having significantly more positive d13Cplant values than less water efficient species. The ranges and means of d13Cbody and d13Cplant were statistically indistinguishable from one another suggesting that d13Cbody was primarily a function of local vegetation composition. H. melanostoma d13Cshell reflected the d13Cplant of local vegetation with a positive offset between body/diet and shell of 14.5± 1.4‰. Therefore, in the Gebel al-Akhdar where only C3 plants are present, highermeand13C shell values likely reflect greater abundances ofwater-efficientC3 plants in the snails diet and therefore in the landscape, whilst lower mean d13Cshell values likely reflect the consumption of less water-efficient C3 plants. The distribution of these plants is in turn affected by environmental factors such as rainfall. These findings can be applied to archaeological and geological shell deposits to reconstruct late Pleistocene to Holocene vegetation change in the southeast Mediterranean

A two-species model of a two-dimensional sandpile surface: a case of asymptotic roughening

We present and analyze a model of an evolving sandpile surface in (2 + 1) dimensions where the dynamics of mobile grains ({\rho}(x, t)) and immobile clusters (h(x, t)) are coupled. Our coupling models the situation where the sandpile is flat on average, so that there is no bias due to gravity. We find anomalous scaling: the expected logarithmic smoothing at short length and time scales gives way to roughening in the asymptotic limit, where novel and non-trivial exponents are found.Comment: 7 Pages, 6 Figures; Granular Matter, 2012 (Online

The social consequences of minor innovations in construction

Innovation studies in construction focus on a desire to increase economics and efficiency at a large scale. This has resulted in a skewed perspective that sees only major corporations with substantial R&D resources, complex projects, or national interests at the heart of innovation. By adopting anthropological methods, it becomes possible to examine the two aims of this paper: to demonstrate that an accumulation of minor innovations can have significant consequences; and to show that these are inherently social rather than purely economic. Results come from fieldwork studying the improvisatory house-building practices of the Kelabit people of rural Borneo, tracing changes to the technologies used for roofing and foundations, and describes how these are mutually entangled with new social structures. The conclusion is that we should think more broadly about the forms and effects of innovation in construction, and recognise the significance of improvisation at the level of the individual or small group

Higher twists and αs(MZ)\alpha_s(M_Z) extractions from the NNLO QCD analysis of the CCFR data for xF3xF_3 structure function

A detailed next-to-next-to-leading order (NNLO) QCD analysis is performed for the experimental data of the CCFR collaboration for the $xF_3$ structure function. Theoretical ambiguities of the results of our NNLO fits are estimated by application of the Pad\'e resummation technique and variation of the factorization and renormalization scales. The NNLO and N$^3$LO $\alpha_s(Q^2)$ $\bar{MS}$-matching conditions are used. In the process of the fits we are taking into account of twist-4 $1/Q^2$-terms. We found that the amplitude of the $x$-shape of the twist-4 factor is decreasing in NLO and NNLO, though some remaining twist-4 structure seems to retain in NNLO in the case when statistical uncertainties are taken into account. The question of the stability of these results to the application of the [0/2] Pad\'e resummation technique is considered. Our NNLO results for $\alpha_s(M_Z)$ values, extracted from the CCFR $xF_3$ data, are $\alpha_s(M_Z)=0.118 \pm 0.002 (stat) \pm 0.005 (syst)\pm 0.003 (theory)$ provided the twist-4 contributions are fixed through the infrared renormalon model and $\alpha_s(M_Z)=0.121^{+0.007}_{0.010}(stat)\pm 0.005 (syst) \pm 0.003 (theory)$ provided the twist-4 terms are considered as free parameters.Comment: 33 pages LaTeX, 3 ps figures; minor misprints are eliminated, 2 new referencies are added; accepted for publication in Nucl. Phys.

Changing patterns of eastern Mediterranean shellfish exploitation in the Late Glacial and Early Holocene: Oxygen isotope evidence from gastropod in Epipaleolithic to Neolithic human occupation layers at the Haua Fteah cave, Libya

The seasonal pattern of shellfish foraging at the archaeological site of Haua Fteah in the Gebel Akhdar, Libya was investigated from the Epipaleolithic to the Neolithic via oxygen isotope (d18O) analyses of the topshell Phorcus (Osilinus) turbinatus. To validate this species as faithful year-round palaeoenvironmental recorder, the intra-annual variability of d18O in modern shells and sea water was analysed and compared with measured sea surface temperature (SST). The shells were found to be good candidates for seasonal shellfish forging studies as they preserve nearly the complete annual SST cycle in their shell d18O with minimal slowing or stoppage of growth. During the terminal Pleistocene Early Epipaleolithic (locally known as the Oranian, with modeled dates of 17.2-12.5 ka at 2sigma probability, Douka et al., 2014), analysis of archaeological specimens indicates that shellfish were foraged year-round. This complements other evidence from the archaeological record that shows that the cave was more intensively occupied in this period than before or afterwards. This finding is significant as the period of the Oranian was the coldest and driest phase of the last glacial cycle in the Gebel Akhdar, adding weight to the theory that the Gebel Akhdar may have served as a refugium for humans in North Africa during times of global climatic extremes. Mollusc exploitation in the Latest Pleistocene and Early Holocene, during the Late Epipaleolithic (locally known as the Capsian, c. 12.7 to 9 ka) and the Neolithic (c. 8.5 to 5.4 ka), occurred predominantly during winter. Other evidence from these archaeological phases shows that hunting activities occurred during the warmer months. Therefore, the timing of Holocene shellfish exploitation in the Gebel Akhdar may have been influenced by the seasonal availability of other resources at these times and possibly shellfish were used as a dietary supplement when other foods were less abundant

Metagenomics combined with activity-based proteomics point to gut bacterial enzymes that reactivate mycophenolate

Mycophenolate mofetil (MMF) is an important immunosuppressant prodrug prescribed to prevent organ transplant rejection and to treat autoimmune diseases. MMF usage, however, is limited by severe gastrointestinal toxicity that is observed in approximately 45% of MMF recipients. The active form of the drug, mycophenolic acid (MPA), undergoes extensive enterohepatic recirculation by bacterial beta-glucuronidase (GUS) enzymes, which reactivate MPA from mycophenolate glucuronide (MPAG) within the gastrointestinal tract. GUS enzymes demonstrate distinct substrate preferences based on their structural features, and gut microbial GUS enzymes that reactivate MPA have not been identified. Here, we compare the fecal microbiomes of transplant recipients receiving MMF to healthy individuals using shotgun metagenomic sequencing. We find that neither microbial composition nor the presence of specific structural classes of GUS genes are sufficient to explain the differences in MPA reactivation measured between fecal samples from the two cohorts. We next employed a GUS-specific activity-based chemical probe and targeted metaproteomics to identify and quantify the GUS proteins present in the human fecal samples. The identification of specific GUS enzymes was improved by using the metagenomics data collected from the fecal samples. We found that the presence of GUS enzymes that bind the flavin mononucleotide (FMN) is significantly correlated with efficient MPA reactivation. Furthermore, structural analysis identified motifs unique to these FMN-binding GUS enzymes that provide molecular support for their ability to process this drug glucuronide. These results indicate that FMN-binding GUS enzymes may be responsible for reactivation of MPA and could be a driving force behind MPA-induced GI toxicity.Bio-organic Synthesi

Prenatal cortisol exposure impairs adrenal function but not glucose metabolism in adult sheep

Adverse environmental conditions before birth are known to program adult metabolic and endocrine phenotype in several species. However, whether increments in fetal cortisol concentrations of the magnitude commonly seen in these conditions can cause developmental programming remains unknown. Thus, this study investigated the outcome of physiological increases in fetal cortisol concentrations on glucose-insulin dynamics and pituitary-adrenal function in adult sheep. Compared to saline treatment, intravenous fetal cortisol infusion for 5 days in late gestation did not affect birthweight but increased lamb body weight at 1-2 weeks after birth. Adult glucose dynamics, insulin sensitivity and insulin secretion were unaffected by prenatal cortisol overexposure, assessed by glucose tolerance tests, hyperinsulinaemic-euglycaemic clamps and acute insulin administration. In contrast, prenatal cortisol infusion induced adrenal hypo-responsiveness in adulthood with significantly reduced cortisol responses to insulin-induced hypoglycaemia and exogenous adrenocorticotropic hormone (ACTH) administration relative to saline treatment. The area of adrenal cortex expressed as a percentage of the total cross-sectional area of the adult adrenal gland was also lower after prenatal cortisol than saline infusion. In adulthood, basal circulating ACTH but not cortisol concentrations were significantly higher in the cortisol than saline treated group. The results show that cortisol overexposure before birth programs pituitary-adrenal development with consequences for adult stress responses. Physiological variations in cortisol concentrations before birth may, therefore, have an important role in determining adult phenotypical diversity and adaptability to environmental challenges

Psychosocial stress and brain function in adolescent psychopathology

Objective: To explore how conduct, hyperactivity/inattention, and emotional symptoms are associated with neural reactivity to social-emotional stimuli, and the extent to which psychosocial stress modulates these relationships. Method: Participants were community adolescents recruited as part of the European IMAGEN study. Bilateral amygdala regions of interest were used to assess the relationship between the three symptom domains with fMRI neural reactivity during passive viewing of dynamic angry and neutral facial expressions. Exploratory functional connectivity and whole-brain multiple regression approaches were used to analyze how the symptoms and psychosocial stress relate to other brain regions. Results: In response to the social-emotional stimuli, adolescents with high levels of conduct or hyperactivity/inattention symptoms showed hyperactivity of the amygdala, and several regions across the brain, when they experienced a greater number of stressful life events. This effect was not observed with emotional symptoms. A cluster in the mid-cingulate was found to be common to both conduct problems and hyperactivity symptoms. Exploratory functional connectivity analyses suggested amygdala-precuneus connectivity is associated with hyperactivity/inattention symptoms. Conclusions: The results link hyperactive amygdala responses, and regions critical for top-down emotional processing, with high levels of psychosocial stress in individuals with greater conduct and hyperactivity/inattention symptoms. This work highlights the importance of studying how psychosocial stress impacts functional brain responses to social-emotional stimuli, particularly in adolescents with externalizing symptoms