Medicines optimisation for young people with juvenile arthritis and other long-term conditions:system-level barriers to engagement

To explore the views of pharmacy and rheumatology stakeholders about system-related barriers to medicines optimisation activities with young people with long-term conditions. A three-phase consensus-building study comprising (1) focus groups with community and hospital pharmacists; (2) semi-structured telephone interviews with lay and professional adolescent rheumatology stakeholders and pharmacy policymakers, and (3) multidisciplinary discussion groups with community and hospital pharmacists and rheumatology staff. Qualitative verbatim transcripts from phases 1 and 2 were subjected to framework analysis. Themes from phase 1 underpinned a briefing for phase 2 interviewees. Themes from phases 1 and 2 generated elements of good pharmacy practice and current/future pharmacy roles for ranking in phase 3. Results from phase 3 prioritisation and ranking exercises were captured on self-completion data collection forms, entered into an Excel spreadsheet and subjected to descriptive statistical analysis. Institutional ethical approval was given by Aston University Health and Life Sciences Research Ethics Committee. Four focus groups were conducted with 18 pharmacists across England, Scotland and Wales (7 hospital, 10 community and 1 community/public health). Fifteen stakeholders took part in telephone interviews (3 pharmacist commissioners; 2 pharmacist policymakers; 2 pharmacy staff members (1 community and 1 hospital); 4 rheumatologists; 1 specialist nurse, and 3 lay juvenile arthritis advocates). Twenty-five participants took part in three discussion groups in adolescent rheumatology centres across England and Scotland (9 community pharmacists; 4 hospital pharmacists; 6 rheumatologists; 5 specialist nurses, and 1 physiotherapist). In all phases of the study, system-level issues were acknowledged as barriers to more engagement with young people and families. Community pharmacists in the focus groups reported that opportunities for engaging with young people were low if parents collected prescriptions alone, which was agreed by other stakeholders. Moreover, institutional/company prescription collection policies – an activity largely disallowed for a young person under 16 without an accompanying parent - were identified by hospital and community pharmacists as barriers to open discussion and engagement. Few community pharmacists reported using Medicines Use Review (England/Wales) or Chronic Medication Service (Scotland) as a medicines optimisation activity with young people; many were unsure about consent procedures. Despite these limitations, rheumatology stakeholders ranked highly the potential of pharmacists empowering young people with general health care skills, such as repeat prescription ordering. The pharmacy profession lacks vision for its role in the care of young people with long-term conditions. Pharmacists and rheumatology stakeholders identified system-level barriers to more engagement with young people who take medicines regularly. We acknowledge that the modest number of participants may have had a specific interest and thus bias for the topic, but this underscores their frank admission of the challenges. Professional guidance and policy, practice frameworks and institutional/company policies must promote flexibility for pharmacy staff to recognise and empower young people who are able to give consent and take responsibility for medicines activities. This will increase mutual confidence and trust, and foster pharmacy’s role in teaching general health care skills. In this way, pharmacists will be able to build long-term relationships with young people and families.

Improving publicly funded human services: Incorporating capacity building into the contracting relationship between Children's Services Councils and nonprofit organizations

This qualitative two-site case study examined the capacity building practices that Children’s Services Councils (CSCs), independent units of local government, provide to nonprofit organizations (NPOs) contracted to deliver human services. The contracting literature is replete with recommendations for government to provide capacity building to contracted NPOs, yet there is a dearth of scholarship on this topic. The study’s purpose was to increase the understanding of capacity building provided in a local government contracting setting. Data collection consisted primarily of in-depth interviews and focus groups with 73 staff from two CSCs and 28 contracted NPOs. Interview data were supplemented by participant observation and review of secondary data. The study analyzed capacity building needs, practices, influencing factors, and outcomes. The study identified NPO capacity building needs in: documentation and reporting, financial management, program monitoring and evaluation, participant recruitment and retention, and program quality. Additionally, sixteen different types of CSC capacity building practices were identified. Results indicated that three major factors impacted CSC capacity building: CSC capacity building goals, the relationship between the CSC and NPOs, and the level of NPO participation. Study results also provided insight into the dynamics of the CSC capacity building process, including unique problems, challenges, and opportunities as well as necessary resources. The results indicated that the CSCs’ relational contracting approach facilitated CSC capacity building and that CSC contract managers were central players in the process. The study provided evidence that local government agencies can serve as effective builders of NPO capacity. Additionally, results indicated that much of what is known about capacity building can be applied in this previously unstudied capacity building setting. Finally, the study laid the groundwork for future development of a model for capacity building in a local government contracting setting.

Isolation and characterization of the U1 and U2 snRNAs in the silk gland of the 5th instar larval stage silk moth Bombyx mori

In isolation and characterization studies, expression level U1 and U2 snRNA isoforms were obtained from the 5th instar larval stage silk gland (SG). The DNA content of the SG cells is approximately 200,000-fold higher compared to the usual (2N) somatic cells of B. mori due to endoreduplication. In this study, the existence of U1 and U2 snRNA isoforms in the SG of the organism is investigated. Bombyx mori U1 and U2-specific RT-PCR libraries from the silk gland were generated. Five U1 and eight U2 isoforms were isolated and characterized. Nucleotide differences, structural alterations, as well as protein and RNA interaction sites were analyzed in these variants. For the U1 snRNA variants, they were compared to the previously reported BmN isoforms. In all these U-snRNA variants, polymorphic sites do not predominate at the core of known functional sequences, which were interspecifically conserved. Variant sites and inter-species differences are located in moderately conserved regions. Free energy (ΔG) values for the entire U1 and U2 snRNA secondary structures and for the individual stem/loops domains of the isoforms were generated and compared to determine their structural stability. This will be the first time that U1 and U2 variants are shown specific for a development stage (larval) other than embryonic or adult. ^ Using phylogenetic analysis, evolutionary trees were generated for the U1 and U2 snRNAs using animal, plant, protista and fungal species. The resulting trees were boostrapped for robustness and rooted with the self-splicing RNA group II intron sequence from the cyanobacterium Calothrix. Using phylogenetic analyses, possible structural and functional evolutionary interdependence between the U1 and U2 snRNAs was investigated. ^

The relationship of culturally responsive instruction and the reading comprehension and attitude of struggling urban adolescent readers

Culturally responsive instruction refers to the identification of relevant cultural aspects of students' lives and infusion of these into the curriculum. This instructional approach assumes that a culturally appropriate curriculum can potentially motivate, engage, and lead students to higher rates of achievement. This quasi-experimental study (N=44) investigated the relationship of culturally responsive instruction and the reading comprehension and attitude of struggling urban adolescent readers. The study incorporated the use of culturally responsive instruction using culturally relevant literature (CRL), the Bluford Series Novels, as authentic texts of instruction. Participants were seventh grade reading students at a Title I middle school in South Florida. After a baseline period, two different classes were taught for 8 weeks using different methods. One class formed the experimental group ( n=22) and the other class formed the comparison group (n =22). The CRI curriculum for the experimental group embraced the socio-cultural perspective through the use of small discussion groups in which students read and constructed meaning with peers through interaction with the Bluford Series Novels; gave written responses to multiple strategies according to SCRAP - Summarize, Connect, Reflect, Ask Questions, Predict; responded to literal and inferential questions, while at the same time validating their responses through evidence from the text. The Read XL (basal reader) curriculum of the comparison group utilized a traditional form of instruction which incorporated the reading of passages followed by responses to comprehension questions, and teacher-led whole group discussion. The main sources of data were collected from the Gates-MacGinitie Reading Tests, the Florida Assessments for Instruction in Reading (FAIR), and the Rhody Secondary Reading Attitude Assessment. Statistical analyses were performed using Repeated Measures ANOVAs. Findings from the study revealed that the experimental participants' reading attitudes and FAIR comprehension scores increased when compared to the comparison group. Overall, the results from the study revealed that culturally responsive instruction can potentially foster reading comprehension and a more positive attitude towards reading. However, a replication of this study in other settings with a larger, more randomized sample size and a greater ethnic variation is needed in order to make full generalizations.

Towards a model for exploring the relationship between managerial decision problems and decision support opportunities

The organisational decision making environment is complex, and decision makers must deal with uncertainty and ambiguity on a continuous basis. Managing and handling decision problems and implementing a solution, requires an understanding of the complexity of the decision domain to the point where the problem and its complexity, as well as the requirements for supporting decision makers, can be described. Research in the Decision Support Systems domain has been extensive over the last thirty years with an emphasis on the development of further technology and better applications on the one hand, and on the other hand, a social approach focusing on understanding what decision making is about and how developers and users should interact. This research project considers a combined approach that endeavours to understand the thinking behind managers’ decision making, as well as their informational and decisional guidance and decision support requirements. This research utilises a cognitive framework, developed in 1985 by Humphreys and Berkeley that juxtaposes the mental processes and ideas of decision problem definition and problem solution that are developed in tandem through cognitive refinement of the problem, based on the analysis and judgement of the decision maker. The framework facilitates the separation of what is essentially a continuous process, into five distinct levels of abstraction of manager’s thinking, and suggests a structure for the underlying cognitive activities. Alter (2004) argues that decision support provides a richer basis than decision support systems, in both practice and research. The constituent literature on decision support, especially in regard to modern high profile systems, including Business Intelligence and Business analytics, can give the impression that all ‘smart’ organisations utilise decision support and data analytics capabilities for all of their key decision making activities. However this empirical investigation indicates a very different reality.

Contributions of Dorsal/Ventral Hippocampus and Dorsolateral/Dorsomedial Striatum to Interval Timing

Humans and animals have remarkable capabilities in keeping time and using time as a guide to orient their learning and decision making. Psychophysical models of timing and time perception have been proposed for decades and have received behavioral, anatomical and pharmacological data support. However, despite numerous studies that aimed at delineating the neural underpinnings of interval timing, a complete picture of the neurobiological network of timing in the seconds-to-minutes range remains elusive. Based on classical interval timing protocols and proposing a Timing, Immersive Memory and Emotional Regulation (TIMER) test battery, the author investigates the contributions of the dorsal and ventral hippocampus as well as the dorsolateral and the dorsomedial striatum to interval timing by comparing timing performances in mice after they received cytotoxic lesions in the corresponding brain regions. On the other hand, a timing-based theoretical framework for the emergence of conscious experience that is closely related to the function of the claustrum is proposed so as to serve both biological guidance and the research and evolution of “strong” artificial intelligence. Finally, a new “Double Saturation Model of Interval Timing” that integrates the direct- and indirect- pathways of striatum is proposed to explain the set of empirical findings.

Hippocampal Transcriptomic and Proteomic Alterations in the BTBR Mouse Model of Autism Spectrum Disorder.

Autism spectrum disorders (ASD) are complex heterogeneous neurodevelopmental disorders of an unclear etiology, and no cure currently exists. Prior studies have demonstrated that the black and tan, brachyury (BTBR) T+ Itpr3tf/J mouse strain displays a behavioral phenotype with ASD-like features. BTBR T+ Itpr3tf/J mice (referred to simply as BTBR) display deficits in social functioning, lack of communication ability, and engagement in stereotyped behavior. Despite extensive behavioral phenotypic characterization, little is known about the genes and proteins responsible for the presentation of the ASD-like phenotype in the BTBR mouse model. In this study, we employed bioinformatics techniques to gain a wide-scale understanding of the transcriptomic and proteomic changes associated with the ASD-like phenotype in BTBR mice. We found a number of genes and proteins to be significantly altered in BTBR mice compared to C57BL/6J (B6) control mice controls such as BDNF, Shank3, and ERK1, which are highly relevant to prior investigations of ASD. Furthermore, we identified distinct functional pathways altered in BTBR mice compared to B6 controls that have been previously shown to be altered in both mouse models of ASD, some human clinical populations, and have been suggested as a possible etiological mechanism of ASD, including "axon guidance" and "regulation of actin cytoskeleton." In addition, our wide-scale bioinformatics approach also discovered several previously unidentified genes and proteins associated with the ASD phenotype in BTBR mice, such as Caskin1, suggesting that bioinformatics could be an avenue by which novel therapeutic targets for ASD are uncovered. As a result, we believe that informed use of synergistic bioinformatics applications represents an invaluable tool for elucidating the etiology of complex disorders like ASD.

(Table 1) Determined and theoretical chemical composition of thaumasite of ODP Hole 135-841B

Hole 841B was drilled in the forearc region of the Lau Basin at a water depth of 4810 m. The hole penetrated a roughly 500-m-thick series of Miocene volcanic sediments with a number of basaltic to andesitic units (sills?) varying in thickness between 7 cm and 17 m. The volcanics are slightly to moderately altered and contain analcite, chabazite, natrolite-thompsonite, heulandite (?), prehnite, and quartz as secondary phases. In addition, thaumasite [Ca3Si(OH)6 * 12H2O](SO4)(CO3) was identified in the altered sequence. Sulfur isotope data of two thaumasite separates (+23.5 per mil and +21.1 per mil d34S) indicate a seawater origin of the sulfate sulfur. It is suggested that thaumasite is a product of low-temperature (<60 °C), seawater-derived CaCl2-rich fluids that were almost identical in composition to those presently circulating in the sub-seafloor.

Ketones in hydrothermal petroleums and sediments from Guaymas Basin

The polar compound (NSO) fractions of seabed petroleums and sediment extracts from the Guaymas Basin hydrothermal system have been analyzed by gas chromatography and gas chromatography-mass spectrometry. The oils were collected from the interiors and exteriors of high temperature hydrothermal vents and represent hydrothermal pyrolysates that have migrated to the seafloor by hydrothermal fluid circulation. The downcore samples are representative of both thermally unaltered and thermally altered sediments. The survey has revealed the presence of oxygenated compounds correlated with samples exhibiting a high degree of thermal maturity. Several homologous series of related ketone isomers are enriched in the interiors of the hydrothermal vent samples or in hydrothermally-altered sequences of the downcore sediments (DSDP Holes 477 and 481A). The n-alkanones range in carbon number from C11 to C33 with a Cmax from 14 to 23, distributions that are similar to those of the n-alkanes. The alkan-2-ones are usually in highest concentrations, with lower amounts of 3-, 4-, 5-, 6-, 7- (and higher) alkanones, and they exhibit no carbon number preference (there is an odd carbon number preference of alkanones observed for downcore samples). The alkanones are enriched in the interiors of the hydrothermal vent spires or in downcore hydrothermally-altered sediments, indicating an origin at depth or in the hydrothermal fluids and not from an external biogenic deposition. Minor amounts of C13 and C18 isoprenoid ketones are also present. Simulation of the natural hydrothermal alternation process by laboratory hydrous pyrolysis techniques provided information regarding the mode of alkanone formation. Hydrous pyrolysis of n-C32H66 at 350°C for 72 h with water only or water with inorganic additives has been studied using a stainless steel reaction vessel. In each experiment oxygenated hydrocarbons, including alkanones, were formed from the n-alkane. The product distributions indicate a reaction pathway consisting of n-alkanes and a-olefins as primary cracking products with internal olefins and alkanones as secondary reaction products. Hydrous pyrolyses of Messel shale spiked with molecular probes have been performed under similar time and temperature constraints to produce alkanone distributions like those found in the hydrothermal vent petroleums.

Life-history traits of two Salvelinus species and mercury concentrations in fish and prey in ten Canadian lakes (2006-2008)

Mercury concentrations ([Hg]) in Arctic food fish often exceed guidelines for human subsistence consumption. Previous research on two food fish species, Arctic char (Salvelinus alpinus) and lake trout (Salvelinus namaycush), indicates that anadromous fish have lower [Hg] than nonanadromous fish, but there have been no intraregional comparisons. Also, no comparisons of [Hg] among anadromous (sea-run), resident (marine access but do not migrate), and landlocked (no marine access) life history types of Arctic char and lake trout have been published. Using intraregional data from 10 lakes in the West Kitikmeot area of Nunavut, Canada, we found that [Hg] varied significantly among species and life history types. Differences among species-life history types were best explained by age-at-size and C:N ratios (indicator of lipid); [Hg] was significantly and negatively related to both. At a standardized fork length of 500 mm, lake trout had significantly higher [Hg] (mean 0.17 µg/g wet wt) than Arctic char (0.09 µg/g). Anadromous and resident Arctic char had significantly lower [Hg] (each 0.04 µg/g) than landlocked Arctic char (0.19 µg/g). Anadromous lake trout had significantly lower [Hg] (0.12 µg/g) than resident lake trout (0.18 µg/g), but no significant difference in [Hg] was seen between landlocked lake trout (0.21 µg/g) and other life history types. Our results are relevant to human health assessments and consumption guidance and will inform models of Hg accumulation in Arctic fish.

A monster that lives in our lives - experiences of caregivers of people with motor neuron disease and identifying avenues for support.

Background A developing body of evidence has provided valuable insight into the experiences of caregivers of people with motor neuron disease; however, understandings of how best to support caregivers remain limited.

Aim This study sought to understand concepts related to the motor neuron disease caregiver experience which could inform the development of supportive interventions.

Design A qualitative thematic analysis of a one-off semistructured interview with caregivers was undertaken.

Setting/participants Caregivers of people with motor neuron disease were recruited from a progressive neurological diseases clinic in Melbourne, Australia.

Results 15 caregivers participated. Three key themes were identified: (1) The Thief: the experience of loss and grief across varied facets of life; (2) The Labyrinth: finding ways to address ever changing challenges as the disease progressed; (3) Defying fate: being resilient and hopeful as caregivers tried to make the most of the time remaining.

Conclusions Caregivers are in need of more guidance and support to cope with experiences of loss and to adapt to changeable care giving duties associated with disease progression. Therapeutic interventions which target these experiences of loss and change are worth investigation.