An Occupation-Based Clinic Makeover: Perceptions and Experiences of Occupational Therapists

Background: Researchers sought to discover the experiences of occupational therapists transitioning from existing clinical practice to exclusively occupation-based approaches. Method: This phenomenological study captured the experiences of clinicians as exercise-based equipment was temporarily removed from the rehabilitation gym and replaced with occupation-based kits. The therapists used the new occupation-based materials with all clients for 4 months and participated in interviews and a focus group. Results: The study yielded a greater understanding therapists’ process and experiences through the themes: (a) challenges to occupation-based practice and (b) occupation-based metamorphosis. Conclusions: The personal and contextual obstacles associated with implementing occupation-based practice hinder occupational therapists’ abilities to practice aligned with the profession’s philosophical beliefs. However, when sufficient supports are in place, therapists traverse the “change curve” and ultimately experience a professional evolution into an occupation-centered paradigm

Genetic Architecture of Intrinsic Antibiotic Susceptibility

BACKGROUND:Antibiotic exposure rapidly selects for more resistant bacterial strains, and both a drug's chemical structure and a bacterium's cellular network affect the types of mutations acquired. METHODOLOGY/PRINCIPAL FINDINGS:To better characterize the genetic determinants of antibiotic susceptibility, we exposed a transposon-mutagenized library of Escherichia coli to each of 17 antibiotics that encompass a wide range of drug classes and mechanisms of action. Propagating the library for multiple generations with drug concentrations that moderately inhibited the growth of the isogenic parental strain caused the abundance of strains with even minor fitness advantages or disadvantages to change measurably and reproducibly. Using a microarray-based genetic footprinting strategy, we then determined the quantitative contribution of each gene to E. coli's intrinsic antibiotic susceptibility. We found both loci whose removal increased general antibiotic tolerance as well as pathways whose down-regulation increased tolerance to specific drugs and drug classes. The beneficial mutations identified span multiple pathways, and we identified pairs of mutations that individually provide only minor decreases in antibiotic susceptibility but that combine to provide higher tolerance. CONCLUSIONS/SIGNIFICANCE:Our results illustrate that a wide-range of mutations can modulate the activity of many cellular resistance processes and demonstrate that E. coli has a large mutational target size for increasing antibiotic tolerance. Furthermore, the work suggests that clinical levels of antibiotic resistance might develop through the sequential accumulation of chromosomal mutations of small individual effect

Combined visual and biochemical analyses confirm depositor and diet for Neolithic coprolites from Skara Brae

Coprolites (fossilized faeces) can provide valuable insights into species’ diet and related habits. In archaeozoological contexts, they are a potential source of information on human-animal interactions as well as human and animal subsistence. However, despite a broad discussion on coprolites in archaeology, such finds are rarely subject to detailed examination by researchers, perhaps due to the destructive nature of traditional analytical methods. Here, we have examined coprolitic remains from the Neolithic (third millennium BCE) settlement at Skara Brae, Orkney, using a range of modern methods: X-ray computed tomography, scanning electron microscopy, lipid and protein analysis (shotgun proteomics of the coprolite matrix as well as collagen peptide mass fingerprinting of isolated bone fragments). This combined approach minimised destructiveness of sampling, leaving sufficient material for subsequent study, while providing more information than traditional morphological examination alone. Based on gross visual examination, coprolites were predominantly attributed to domestic dogs (Canis familiaris), with morphologically identified bone inclusions derived from domestic sheep (Ovis aries) and common voles (Microtus arvalis). Partial dissection of a coprolite provided bone samples containing protein markers akin to those of domestic sheep. Considering the predominance of vertebral and distal limb bone fragments, Skara Brae dogs were probably consuming human butchery or meal refuse, either routinely fed to them or scavenged. The presumably opportunistic consumption of rodents may also have played a role in pest control

Results from an extensive simultaneous broadband campaign on the underluminous active nucleus M81*: further evidence for mass-scaling accretion in black holes

We present the results of a broadband simultaneous campaign on the nearby low-luminosity active galactic nucleus M81*. From February through August 2005, we observed M81* five times using the Chandra X-ray Observatory with the High-Energy Transmission Grating Spectrometer, complemented by ground-based observations with the Giant Meterwave Radio Telescope, the Very Large Array and Very Large Baseline Array, the Plateau de Bure Interferometer at IRAM, the Submillimeter Array and Lick Observatory. We discuss how the resulting spectra vary over short and longer timescales compared to previous results, especially in the X-rays where this is the first ever longer-term campaign at spatial resolution high enough to nearly isolate the nucleus (17pc). We compare the spectrum to our Galactic center weakly active nucleus Sgr A*, which has undergone similar campaigns, as well as to weakly accreting X-ray binaries in the context of outflow-dominated models. In agreement with recent results suggesting that the physics of weakly-accreting black holes scales predictably with mass, we find that the exact same model which successfully describes hard state X-ray binaries applies to M81*, with very similar physical parameters.Comment: 58 pages (preprint version), 22 figures, accepted for publication in the Astrophysical Journa

Individual common variants exert weak effects on the risk for autism spectrum disorders.

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest

Genetic Variants in <i>CPA6</i> and <i>PRPF31</i> are Associated with Variation in Response to Metformin in Individuals with Type 2 Diabetes

Metformin is the first-line treatment for type 2 diabetes (T2D). Although widely prescribed, the glucose-lowering mechanism for metformin is incompletely understood. Here, we used a genome-wide association approach in a diverse group of individuals with T2D from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial to identify common and rare variants associated with HbA1c response to metformin treatment and followed up these findings in four replication cohorts. Common variants in PRPF31 and CPA6 were associated with worse and better metformin response, respectively (P &lt; 5 × 10-6), and meta-analysis in independent cohorts displayed similar associations with metformin response (P = 1.2 × 10-8 and P = 0.005, respectively). Previous studies have shown that PRPF31(+/-) knockout mice have increased total body fat (P = 1.78 × 10-6) and increased fasted circulating glucose (P = 5.73 × 10-6). Furthermore, rare variants in STAT3 associated with worse metformin response (q &lt;0.1). STAT3 is a ubiquitously expressed pleiotropic transcriptional activator that participates in the regulation of metabolism and feeding behavior. Here, we provide novel evidence for associations of common and rare variants in PRPF31, CPA6, and STAT3 with metformin response that may provide insight into mechanisms important for metformin efficacy in T2D

Future research directions on the "elusive" white shark

White sharks, Carcharodon carcharias, are often described as elusive, with little information available due to the logistical difficulties of studying large marine predators that make long-distance migrations across ocean basins. Increased understanding of aggregation patterns, combined with recent advances in technology have, however, facilitated a new breadth of studies revealing fresh insights into the biology and ecology of white sharks. Although we may no longer be able to refer to the white shark as a little-known, elusive species, there remain numerous key questions that warrant investigation and research focus. Although white sharks have separate populations, they seemingly share similar biological and ecological traits across their global distribution. Yet, white shark’s behavior and migratory patterns can widely differ, which makes formalizing similarities across its distribution challenging. Prioritization of research questions is important to maximize limited resources because white sharks are naturally low in abundance and play important regulatory roles in the ecosystem. Here, we consulted 43 white shark experts to identify these issues. The questions listed and developed here provide a global road map for future research on white sharks to advance progress toward key goals that are informed by the needs of the research community and resource managers

Severe neurocognitive and growth disorders due to variation in THOC2, an essential component of nuclear mRNA export machinery

Highly conserved TREX-mediated mRNA export is emerging as a key pathway in neuronal development and differentiation. TREX subunit variants cause neurodevelopmental disorders (NDDs) by interfering with mRNA export from the cell nucleus to the cytoplasm. Previously we implicated four missense variants in the X-linked THOC2 gene in intellectual disability (ID). We now report an additional six affected individuals from five unrelated families with two de novo and threematernally inherited pathogenic or likely pathogenic variants in THOC2 extending the genotypic and phenotypic spectrum. These comprise three rare missense THOC2 variants that affect evolutionarily conserved amino acid residues and reduce protein stability and two with canonical splice-site THOC2 variants that result in C-terminally truncated THOC2 proteins.We present detailed clinical assessment and functional studies on a de novo variant in a female with an epileptic encephalopathy and discuss an additional four families with rare variants in THOC2 with supportive evidence for pathogenicity. Severe neurocognitive features, including movement and seizure disorders, were observed in this cohort. Taken together our data show that even subtle alterations to the canonical molecular pathways such asmRNAexport, otherwise essential for cellular life, can be compatible with life, but lead to NDDs in human

Habitat preferences by individual humpback whale mothers in the Hawaiian breeding grounds vary with the age and size of their calves

We investigated whether calf age and calf size influence habitat choice by humpback whale motherecalf pairs in their breeding grounds. During 1997e2008, we conducted focal follows of motherecalf pairs in Hawaiian waters. Tail-fluke identification photographs and calf lengths (measured through video-grammetry) were obtained. Water depth and sea-bed terrain type were derived from GPS data. Identification photographs were matched so that the habitat choices could be established within breeding seasons. Across 72 motherecalf pairs resighted over various intervals within a breeding season, magnitude of depth change between initial and final sightings increased significantly with resighting interval. There was a significant increase from initial depth to final depth for relatively long resighting intervals (27e51 days), but no significant difference for relatively short resighting intervals (2e26 days). Although there was no preference for sea-bed terrain type by motherecalf pairs at their initial sighting, there was a preference for rugged terrain at their final resighting. A resource selection model indicated that the relative probability of a location being used by a motherecalf pair increased (as a function of water depth and rugged sea-bed terrain type) from initial to final sighting; a finding supported by subsequent tests of habitat preference versus availability. For 96 measured calves, calf length and water depth were positively correlated, even when ordinal day of measurement was controlled for statistically; a finding confirmed by a general linear model that simultaneously investigated the relationship between water depth, sea-bed terrain type, number of escorts, ordinal day and calf size. Thus, both calf age and size influence habitat choice by motherecalf pairs in their breeding grounds. The movement of mothers and their maturing calves into deeper waters where they favour rugged sea-bed terrain appears to be part of a suite of behavioural changes during the pre-migratory phase of residency in the breeding grounds