Staff perceptions following a training programme about reducing psychotropic medication use in adults with intellectual disability : the need for a realistic professional practice framework

Background: Adults with intellectual disability are at higher risk of being administered psychotropic medications. The UK-developed SPECTROM (Short-term PsychoEducation for Carers To Reduce Over Medication of people with intellectual disabilities) training programme educates disability support workers on psychotropic medications and alternatives to these medications. Method: Interviews were conducted with 10 participants who took part in the pilot SPECTROM training programme to elicit their views on the programme and its appropriateness in an Australian context. Results: The key theme was ‘Need for a psychotropic medication practice framework’. Four sub-themes were Broad satisfaction with the SPECTROM training programme; Disability support workers acknowledging the limitations of their scope of practice; Empowering training through prescriptive and reflective methods and; Need for future mentoring from Multi-Disciplinary Team members in the application of new knowledge. Conclusions: Participants felt that whilst they could improve their knowledge and attitudes surrounding psychotropic medication administration for behaviours of concern through SPECTROM training, a national practice framework is needed to execute its goals at scale

Short-Term Psycho-Education for Caregivers to Reduce Overmedication of People with Intellectual Disabilities (SPECTROM): An Australian Feasibility Study

Many people with intellectual disability display behaviours of concern. Oftentimes, these are managed using a range of approaches that includes the use of psychotropic medications even though the person does not have a psychiatric diagnosis. Finding ways to reduce the use of psychotropic medication is important, and disability support workers play an important role in achieving this goal. This study trained disability support workers about psychotropic medications and alternatives to them using the SPECTROM training program and resources. Data collected included measuring disability support workers' knowledge and attitude, in addition to exploring the appropriateness of the training program. Although disability support workers' knowledge increased after the training program, their attitudes did not change. The SPECTROM training program is feasible in the Australian context despite the need for an Australian practice framework in this area

GAMA/G10-COSMOS/3D-HST: The 0<z<5 cosmic star-formation history, stellar- and dust-mass densities

We use the energy-balance code MAGPHYS to determine stellar and dust masses, and dust corrected star-formation rates for over 200,000 GAMA galaxies, 170,000 G10-COSMOS galaxies and 200,000 3D-HST galaxies. Our values agree well with previously reported measurements and constitute a representative and homogeneous dataset spanning a broad range in stellar mass (10^8---10^12 Msol), dust mass (10^6---10^9 Msol), and star-formation rates (0.01---100 Msol per yr), and over a broad redshift range (0.0 < z < 5.0). We combine these data to measure the cosmic star-formation history (CSFH), the stellar-mass density (SMD), and the dust-mass density (DMD) over a 12 Gyr timeline. The data mostly agree with previous estimates, where they exist, and provide a quasi-homogeneous dataset using consistent mass and star-formation estimators with consistent underlying assumptions over the full time range. As a consequence our formal errors are significantly reduced when compared to the historic literature. Integrating our cosmic star-formation history we precisely reproduce the stellar-mass density with an ISM replenishment factor of 0.50 +/- 0.07, consistent with our choice of Chabrier IMF plus some modest amount of stripped stellar mass. Exploring the cosmic dust density evolution, we find a gradual increase in dust density with lookback time. We build a simple phenomenological model from the CSFH to account for the dust mass evolution, and infer two key conclusions: (1) For every unit of stellar mass which is formed 0.0065---0.004 units of dust mass is also formed; (2) Over the history of the Universe approximately 90 to 95 per cent of all dust formed has been destroyed and/or ejected

ASAR15, A cis-acting locus that controls chromosome-wide replication timing and stability of human chromosome 15.

DNA replication initiates at multiple sites along each mammalian chromosome at different times during each S phase, following a temporal replication program. We have used a Cre/loxP-based strategy to identify cis-acting elements that control this replication-timing program on individual human chromosomes. In this report, we show that rearrangements at a complex locus at chromosome 15q24.3 result in delayed replication and structural instability of human chromosome 15. Characterization of this locus identified long, RNA transcripts that are retained in the nucleus and form a "cloud" on one homolog of chromosome 15. We also found that this locus displays asynchronous replication that is coordinated with other random monoallelic genes on chromosome 15. We have named this locus ASynchronous replication and Autosomal RNA on chromosome 15, or ASAR15. Previously, we found that disruption of the ASAR6 lincRNA gene results in delayed replication, delayed mitotic condensation and structural instability of human chromosome 6. Previous studies in the mouse found that deletion of the Xist gene, from the X chromosome in adult somatic cells, results in a delayed replication and instability phenotype that is indistinguishable from the phenotype caused by disruption of either ASAR6 or ASAR15. In addition, delayed replication and chromosome instability were detected following structural rearrangement of many different human or mouse chromosomes. These observations suggest that all mammalian chromosomes contain similar cis-acting loci. Thus, under this scenario, all mammalian chromosomes contain four distinct types of essential cis-acting elements: origins, telomeres, centromeres and "inactivation/stability centers", all functioning to promote proper replication, segregation and structural stability of each chromosome

Chromosome rearrangements and delayed replication of a Cre/loxP-mediated deletion (∼135 kb) in chromosome 15.

<p>A) Secondary rearrangements of chromosome 15. Δ268-4f cells were processed for DNA FISH using a chromosome 15 WCP, and the DNA was stained with DAPI. Rearrangements involving chromosome 15 are indicated with arrows. Non-rearranged chromosome 15 s are indicated with asterisks. B) Schematic diagram of the BrdU Terminal Label replication-timing assay <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004923#pgen.1004923-Smith2" target="_blank">[23]</a>. Cells were exposed to BrdU for either 4.5 or 6 hours, harvested for mitotic cells, and processed for BrdU incorporation and DNA FISH to identify chromosome 15. C) BrdU-WCP assay on cells containing an ∼135 kb distal deletion in chromosome 15. Δ268-4f cells were exposed to BrdU for 4.5 hours, harvested for mitotic cells, stained with an anti-BrdU antibody (green), and processed for DNA FISH with a chromosome 15 WCP (CHR 15; red). The DNA was stained with DAPI. Two different chromosome 15 secondary rearrangements are indicated with arrows. The inset shows the derivative chromosome 15 with the asterisk, with the BrdU staining and WCP shown in separate images. The brackets highlight the non-chromosome 15 DNA. D–G) BrdU-BAC assay on cells containing an ∼135 kb distal deletion in chromosome 15. Δ268-4c cells were exposed to BrdU for 4.5 hours, harvested for mitotic cells, stained with an anti-BrdU antibody (green), and processed for DNA FISH with a chromosome 15 centromeric probe (red) plus a BAC (CTD-2299E17; red) from the deleted region. The DNA was stained with DAPI (white in panel D or blue in panels E–G). The arrows mark the centromeric signals, and the arrowheads mark the BAC signals. The asterisks mark short arms of the deleted chromosome 15 s, which contain BrdU incorporation.</p

The Cre/loxP-mediated deletions occurred on the expressed allele of <i>ASAR15</i>.

<p>P268 (panel A) and Δ268-4 g (panel B) cells were subjected to RNA FISH using the H1 (green) and E4 (red) probes to detect RNA. Images of the RNA hybridization signals were obtained, and the coordinates of individual cells were recorded; the slides were subsequently processed for DNA FISH (BACs CTD-2299E17 plus BAC-CTD-2117F7) and new images of the DNA hybridization were captured for the same cells. The DNA FISH step included an RNAase step, which eliminated the RNA FISH signals. The DNA FISH hybridization signal was pseudo-colored purple for clarity, and the nuclear DNA was stained with DAPI (blue). Representative images from three different P268 and Δ268-4 g cells (#1–3) are shown in each panel (A and B). The arrowheads mark the coincident sites of hybridization detected by both probes. The arrows mark the sites of hybridization with the H1 probe that was not coincident with a site of hybridization with the E4 probe in Δ268-4 g cells (panel B). The asterisks mark the sites of DNA hybridization that lacked corresponding RNA hybridization signals from either H1 or E4 probes.</p

Delayed replication of chromosome 15 with an Cre/loxP-mediated ∼161 kb distal deletion.

<p>A–F) Δ268-4 g cells were incubated with BrdU for 6 hours, harvested for mitotic cells, stained with an antibody to BrdU (green) and processed for DNA FISH using a chromosome 15 centromeric probe (red) plus BAC CTD-2299E17 (red). The chromosomal DNA was stained with DAPI (blue). A and B) A metaphase spread containing three chromosome 15 s (i, ii, and iii). C) The three chromosome 15 s from panel B were cut out and aligned showing the BrdU and FISH signals in separate images. The asterisk marks the location of the deletion in the chromosome marked i, and the arrows mark the location of the BAC hybridization signals on chromosomes ii and iii. D) Pixel intensity profiles of the BrdU incorporation (green), and DAPI (blue) staining along the three chromosome 15 s from panel B. E) The pixel intensity (average intensity x area) for each chromosome, i, ii, and iii, showing the total amount of BrdU incorporation or DAPI staining. F) Quantification of the BrdU incorporation in multiple cells. The red and blue bars represent deleted and non-deleted chromosome 15 s, respectively, in 7 different cells. G) Instability of chromosome 15 containing an ∼161 kb Cre-loxP deletion. Mitotic Δ268-4e cells were processed for DNA FISH with a chromosome 15 WCP, and the chromosomal DNA was stained with DAPI. Rearrangements involving chromosome 15 are indicated with arrows, and non-rearranged chromosome 15 s are indicated with asterisks.</p

Cre/loxP-mediated chromosome 15 rearrangements.

#<p>The number of clones that showed DRT/DMC (total clones scored).</p>q<p>The number of clones that showed>10% of rearrangements of chromosome 15 (total clones scored).</p><p>*At least one clone with>90% of cells containing chromosome 15 rearrangements.</p><p>Cre/loxP-mediated chromosome 15 rearrangements.</p

Coordinated random asynchronous replication on chromosome 15.

<p>A–C) ReTiSH assay on rDNA loci in PBLs. PBLs were labeled with BrdU for 14 (A) or 6 (B) hours, arrested in metaphase, and subjected to ReTiSH using an 18S rDNA probe (red). The chromosome 15 s were identified using a centromeric probe (green), and the chromosomal DNA was detected with DAPI. A and B) The DAPI images of the chromosomes were inverted and the banding patterns were used to identify all of the ReTiSH positive chromosomes. The arrows mark the chromosome 15 s, and the arrowheads mark the other four chromosomes containing rDNA clusters (13, 14, 21, and 22). C) The ReTiSH signals for the rDNA (red) and chromosome 15 centromeric (green) probes from the 14 (panel A) and 6 (panel B) hour time points are shown. The early and late replicating chromosome 15 s are indicated for the 6 hour time point. D) ReTiSH assay using an <i>ASAR15</i> BAC (CTD-2299E17; red), an rDNA probe (red), and a chromosome 15 centromeric probe (green). The <i>ASAR15</i> and rDNA probes show hybridization signals to the same chromosome 15 homolog at the 6 hour time point. E) ReTiSH assay using an <i>ASAR15</i> BAC (CTD-2299E17; red), a <i>MYO1E</i> BAC (RP11-1089J12; green) and a chromosome 15 centromeric probe (red). The <i>ASAR15</i> BAC and the <i>MYO1E</i> BACs show hybridization signals to the same chromosome 15 homolog at the 6 hour time point. D and E) The early and late replicating chromosome 15 s are indicated.</p

Differential allelic expression of <i>ASAR15</i>.

<p>A) A schematic diagram of <i>SCAPER</i>, <i>MIR3713</i>, RNA FISH probes, and five of the distal deletions in chromosome 15. The genomic location (in megabases), the exon-intron structure of <i>SCAPER</i>, the location of 9 fosmids [G248P87971D1 (D1), G248P81306H3 (H3), G248P82406H1 (H1), G248P87518F5 (F5), G248P82172E4 (E4), G248P8912C5 (C5), G248P89264C4 (C4), G248P88942F8 (F8), G248P80481A4 (A4)] used for RNA FISH, and the location of the five smallest distal deletions are shown. The fosmids that detect (green) or do not detect (red) RNA are indicated. B–D) Monoallelic expression of <i>ASAR15</i> in HTD114 cells. HTD114 cells were subjected to RNA FISH using a fosmid (E4 RNA; green) to detect RNA. Images of the RNA hybridization signals were obtained, and the coordinates of individual cells were recorded. Slides were subsequently processed for DNA FISH using a chromosome 15 centromeric probe (CHR15 cen; red) and new images of the DNA hybridization were captured for the same cells. E–G) P268 cells were processed for RNA-DNA FISH using the H1 probe to detect RNA, plus BAC CTD-2299E17 to detect DNA. H-M) RNA-DNA FISH using a pool of fosmid probes (D1, H3, H1, F5, E4, C5, and C4) to detect RNA (green) and a chromosome 15 paint to detect DNA (red). Panels H–J and K-M represent two different cells with the images shown in separate or merged panels. The arrowheads mark the chromosome 15s. N–P) Primary HFFs were processed for RNA-DNA FISH using probe E4 to detect RNA, plus BAC CTD-2117F7 to detect DNA. B–J) The nuclear DNA was stained with DAPI. Arrowheads mark the location of RNA signals, and asterisks mark the location of the DNA signals that lack corresponding RNA signals. In regions of the slides where the FISH worked well, the D1, H3, H1, F5, E4, C5, and C4 probes detected a positive signal in>90% of the HTD114, P268 and HFF cells. Q) RNA FISH in female HDFs. Female HDF cells were processed for RNA FISH using the H1 <i>ASAR15</i> probe (green) in combination with an XIST (red) probe. The arrows mark the large clouds of RNA detected by the <i>XIST</i> probe and the arrowheads mark hybridization signals detected by the <i>ASAR15</i> probe. The DNA was stained with DAPI.</p