Communicating biosecurity information to Australian-registered veterinarians.

OBJECTIVE: Updating veterinarians (vets) on the latest biosecurity resources, information and alerts is important to ensure protection of domesticated and native animals. This preliminary questionnaire aimed to better understand the communication preferences of Australian-registered vets for biosecurity information, and their trust of these sources. METHODS: An online questionnaire asking vets about their current communication preferences for biosecurity information, and their level of trust of these was created and distributed to Australian-registered vets. RESULTS: Survey respondents (158) use and highly trust communication from (in order) vet and animal health organisations, vet surgeons' boards, the scientific literature, and government agencies. CONCLUSIONS: This preliminary study identifies that using vet surgeon's boards, government agencies and vet and animal health organisations may be an effective means for communicating biosecurity information to vets. Future research should consider which sources vets trust and why, to facilitate effective communication to them and the clients they serve.

Congenital Hypothalamic "Hamartoblastoma" Versus "Hamartoma": Suggestions for Neuropathologic Terminology Emanating From a Mid-gestational Autopsy Case of Pallister-Hall Syndrome.

Pallister-Hall syndrome (PHS) is a rare malformative disorder that is due to truncating functional repressor mutations in GLI3. Since the seminal publication in 1980, hypothalamic tumors have been recognized to be a cardinal feature of PHS. In their original description of the neuropathologic features of PHS, Clarren et al. coined the term "hamartoblastoma" to characterize what they deemed to be a dual malformative and neoplastic mass of the hypothalamus. In subsequent published cases/series of PHS, the term "hamartoma" was often substituted for hamartoblastoma given what appeared to be a benign natural history of this lesion. Additional confusion in the literature has ensued since most hypothalamic hamartomas (HH) encountered on the clinical neuropathology service are "isolated" in nature (ie, no other congenital malformations) and present in a very different and stereotypical fashion with gelastic seizures and/or precocious puberty. While genomic investigations of isolated HH have begun to uncover a mutational profile of these cases, GLI3 mutations have only been recognized in a small subset of isolated HH. Herein, we describe the autopsy findings from a 21-week gestational age fetus with features of PHS. Moreover, we provide a detailed description of the hypothalamic tumor affecting this fetus and propose a novel subclassification of HH, distinguishing syndromic from isolated forms based upon the presence or absence of neocortical-like areas.

Supervised learning events: direct observation of procedural skills pilot.

BACKGROUND: Workplace-based assessment (WBA) is the assessment of specialist competence based on what a trainee doctor actually does in the workplace. Between January 2014 and January 2015, all UK occupational medicine (OM) trainees were invited to test a suite of direct observation of procedural skills (DOPS) tools designed in a supervised learning event (SLE) format. The Faculty of Occupational Medicine (FOM) Workplace-Based Assessment Advisory Group (WBAAG) studied feedback on the new format. AIMS: To assess the utility of the redesigned tools, including their acceptability, feasibility, usability and key aspects of their reliability and validity. METHODS: The face and content validity of the new forms were assessed by a comprehension trial (CT), inter-rater reliability by a video scoring exercise and usability and acceptability by an electronic survey of trainees and trainers. RESULTS: The CT of trainees and trainers indicated that the face and content validity of the revised tools were acceptable. Inter-rater reliability video assessments indicated there was consistency of grading among trainers. Sixty-eight per cent of trainees and 95% of trainers agreed that the redesigned tools were an improvement on the current WBA DOPS tools and 83% of trainees indicated the new tools encouraged them to reflect on their performance. CONCLUSIONS: The results from this pilot study provided evidence to support a request to the General Medical Council (GMC) for the new SLE-DOPS forms to be used for WBA in OM. These changes were accepted by the GMC in January 2016 for implementation in April 2016.

Role of morality in the experience of guilt and shame within the armed forces.

OBJECTIVE: Despite advances in our understanding of mental health issues among military forces, a large proportion of military personnel continue to exhibit deployment-related psychological issues. Recent work has identified symptoms of guilt and shame related to moral injury as contributing significantly to combat-related mental health issues. This systematic scoping review explores the association between morality and symptoms of guilt and shame within military forces. METHOD: A search of the literature pertaining to guilt, shame and morality within military samples was conducted. RESULTS: Nineteen articles were selected for review. There is strong evidence linking exposure to and the perceived perpetration of moral transgressions with experiences of guilt and shame. Critically, symptoms of guilt and shame were related to adverse mental health outcomes, particularly the onset of post-traumatic stress disorder (PTSD). No studies have explored moral judgment in conjunction with assessments of guilt or moral injury. CONCLUSION: These findings have important implications for the prevention and treatment of PTSD-related symptoms in military samples. By measuring moral judgment prior to deployment, it may be possible to predict the likelihood of incurring moral injuries and the development of associated symptoms. Early intervention programmes aimed at ameliorating guilt and shame are required to prevent the long-term development of deployment-related psychological distress.

Comprehension of affective prosody in women with post-traumatic stress disorder related to childhood abuse.

OBJECTIVE: Although deficits in memory and cognitive processing are evident in post-traumatic stress disorder (PTSD), difficulties with social cognition and the impact of such difficulties on interpersonal functioning are poorly understood. Here, we examined the ability of women diagnosed with PTSD related to childhood abuse to discriminate affective prosody, a central component of social cognition. METHOD: Women with PTSD and healthy controls (HCs) completed two computer-based tasks assessing affective prosody: (i) recognition (categorizing foreign-language excerpts as angry, fearful, sad, or happy) and (ii) discrimination (identifying whether two excerpts played consecutively had the 'same' or 'different' emotion). The association of performance with symptom presentation, trauma history, and interpersonal functioning was also explored. RESULTS: Women with PTSD were slower than HCs at identifying happiness, sadness, and fear, but not anger in the speech excerpts. The presence of dissociative symptoms was related to reduced accuracy on the discrimination task. An increased severity of childhood trauma was associated with reduced accuracy on the discrimination task and with slower identification of emotional prosody. CONCLUSION: Exposure to childhood trauma is associated with long-term, atypical development in the interpretation of prosodic cues in speech. The findings have implications for the intergenerational transmission of trauma.

Practice and documentation of palliative sedation: a quality improvement initiative.

BACKGROUND: Palliative sedation (ps), the continuous use of sedating doses of medication to intentionally reduce consciousness and relieve refractory symptoms at end of life, is ethically acceptable if administered according to standards of best practice. Procedural guidelines outlining the appropriate use of ps and the need for rigorous documentation have been developed. As a quality improvement strategy, we audited the practice and documentation of ps on our palliative care unit (pcu). METHODS: A pharmacy database search of admissions in 2008 identified, for a subsequent chart review, patients who had received either a continuous infusion of midazolam (≥10 mg/24 h), regular parenteral dosing of methotrimeprazine (≥75 mg daily), or regular phenobarbital. Documentation of the decision-making process, consent, and medication use was collected using a data extraction form based on current international ps standards. RESULTS: Interpretation and comparison of data were difficult because of an apparent lack of a consistent operational definition of ps. Patient records had no specific documentation in relation to ps initiation, to clearly identified refractory symptoms, and to informed consent in 60 (64.5%), 43 (46.2%), and 38 (40.9%) charts respectively. Variation in the medications used was marked: 54 patients (58%) were started on a single agent and 39 (42%), on multiple agents. The 40 patients (43%) started on midazolam alone received a mean daily dose of 21.4 mg (standard deviation: 24.6 mg). CONCLUSIONS: The lack of documentation and standardized practice of ps on our pcu has resulted in a quality improvement program to address those gaps. They also highlight the importance of conducting research and developing clinical guidelines in this area.

Theory of mind performance in women with posttraumatic stress disorder related to childhood abuse.

OBJECTIVE: Key questions remain unaddressed concerning the nature of interpersonal functioning in trauma survivors, including the ability to understand and interpret other people's thoughts and feelings. Here, we investigate theory of mind (ToM) performance of women with PTSD related to childhood abuse in comparison to healthy controls. METHOD: Participants completed two ToM tasks, the Interpersonal Perception Task-15 (IPT-15) and the Reading the Mind in the Eyes Task - Revised (RMET). RESULTS: Relative to controls, women with a history of childhood trauma had difficulty recognizing familial relationships depicted in the IPT-15 (P = 0.005). No other category of the IPT-15 showed significant group differences. In addition, while healthy women displayed faster RMET reaction times to emotionally valenced mental states (positive: P = 0.003; negative: P = 0.016) compared with neutral mental states, the PTSD group showed similar reaction times across all valences. The presence of dissociative symptoms (e.g., disengagement, amnesia, identity dissociation) was strongly associated with hindered accuracy of complex mental state identification and altered perception of kinship interactions. CONCLUSION: Women with PTSD stemming from childhood trauma show changes in ToM abilities particularly those often involved in the interpretation of family interactions. In addition, individuals with PTSD showed slower reaction times during the recognition of complex mental states from emotionally salient facial/eye expressions in comparison with healthy subjects.

University students' notebook computer use: lessons learned using e-diaries to report musculoskeletal discomfort.

The objective of this pilot study was to identify if notebook accessories (ergonomic chair, desktop monitor and notebook riser) combined with a wireless keyboard, mouse and participatory ergonomics training would have the greatest impact on reducing self-reported upper extremity musculoskeletal discomfort in university students. In addition to pre-post computing and health surveys, the Ecological Momentary Assessment was used to capture change in discomfort over time using a personal digital assistant (PDA) as the e-diary. The PDA was programmed with a survey containing 45 questions. Four groups of university students were randomised to either intervention (three external computer accessories) or to control. Participants reported less discomfort with the ergonomic chair and notebook riser based on the pre-post survey data and the e-diary/PDA ANOVA analysis. However, the PDA data, adjusted for the effect of hours per day of computer use, showed no benefit of the chair and limited benefit from the riser. Statement of Relevance:University students' use of notebook computers has increased. This study found evidence of a positive effect of an adjustable chair or notebook riser when combined with ergonomic training on reducing discomfort. Daily notebook computer use of 4 h was confirmed as a risk factor. Without some form of ergonomic intervention, these students are likely to enter the workforce with poor computing habits, which places them on the road to future injuries as technology continues to play a dominant role in their lives.

A collaborative hit-to-lead investigation leveraging medicinal chemistry expertise with high throughput library design, synthesis and purification capabilities.

High throughput screening (HTS) campaigns, where laboratory automation is used to expose biological targets to large numbers of materials from corporate compound collections, have become commonplace within the lead generation phase of pharmaceutical discovery. Advances in genomics and related fields have afforded a wealth of targets such that screening facilities at larger organizations routinely execute over 100 hit-finding campaigns per year. Often, 10(5) or 10(6) molecules will be tested within a campaign/cycle to locate a large number of actives requiring follow-up investigation. Due to resource constraints at every organization, traditional chemistry methods for validating hits and developing structure activity relationships (SAR) become untenable when challenged with hundreds of hits in multiple chemical families per target. To compound the issue, comparison and prioritization of hits versus multiple screens, or physical chemical property criteria, is made more complex by the informatics issues associated with handling large data sets. This article describes a collaborative research project designed to simultaneously leverage the medicinal chemistry and drug development expertise of the Novartis Institutes for Biomedical Research Inc. (NIBRI) and ArQule Inc.'s high throughput library design, synthesis and purification capabilities. The work processes developed by the team to efficiently design, prepare, purify, assess and prioritize multiple chemical classes that were identified during high throughput screening, cheminformatics and molecular modeling activities will be detailed.

A new siglec family member, siglec-10, is expressed in cells of the immune system and has signaling properties similar to CD33.

The siglecs (sialic acid-binding Ig-like lectins) are a distinct subset of the Ig superfamily with adhesion-molecule-like structure. We describe here a novel member of the siglec protein family that shares a similar structure including five Ig-like domains, a transmembrane domain, and a cytoplasmic tail containing two ITIM-signaling motifs. Siglec-10 was identified through database mining of an asthmatic eosinophil EST library. Using the Stanford G3 radiation hybrid panel we were able to localize the genomic sequence of siglec-10 within the cluster of genes on chromosome 19q13.3-4 that encode other siglec family members. We have demonstrated that siglec-10 is an immune system-restricted membrane-bound protein that is highly expressed in peripheral blood leukocytes as demonstrated by Northern, RT-PCR and flow cytometry. Binding assays determined that the extracellular domain of siglec-10 was capable of binding to peripheral blood leukocytes. The cytoplasmic tail of siglec-10 contains four tyrosines, two of which are embedded in ITIM-signaling motifs (Y597 and Y667) and are likely involved in intracellular signaling. The ability of tyrosine kinases to phosphorylate the cytoplasmic tyrosines was evaluated by kinase assay using wild-type siglec-10 cytoplasmic domain and Y-->F mutants. The majority of the phosphorylation could be attributed to Y597 andY667. Further experiments with cell extracts suggest that SHP-1 interacts with Y667 and SHP-2 interacts with Y667 in addition to another tyrosine. This is very similar to CD33, which also binds the phosphatases SHP-1 and SHP-2, therefore siglec-10, as CD33, may be characterized as an inhibitory receptor.

Cytokine-specific transcriptional regulation through an IL-5Ralpha interacting protein.

Cytokine receptors consist of multiple subunits, which are often shared between different receptors, resulting in the functional redundancy sometimes observed between cytokines. The interleukin 5 (IL-5) receptor consists of an IL-5-specific alpha-subunit (IL-5Ralpha) and a signal-transducing beta-subunit (betac) shared with the IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors. In this study, we sought to find a role for the cytoplasmic domain of IL-5Ralpha. We show that syntenin, a protein containing PSD-95/Discs large/zO-1 (PDZ) domains, associates with the cytoplasmic tail of the IL-5Ralpha. Syntenin was found to directly associate with the transcription factor Sox4. Association of syntenin with IL-5Ralpha was required for IL-5-mediated activation of Sox4. These studies identify a mechanism of transcriptional activation by cytokine-specific receptor subunits.

Modified peptide antagonists of interleukin 5 exhibit extended in vivo persistence but restricted species specificity.

AF18748 is disulphide-linked homodimeric peptide with 19 amino acids in each chain that antagonises the action of the eosinophil-specific cytokine, interleukin 5 (IL-5). We have generated a set of N-terminally truncated peptides derived from AF18748 and demonstrated that the first five amino acids of the peptide do not contribute to receptor binding activity. The shortened peptide blocked IL-5-dependent adhesion of eosinophils with an IC(50)of 350 pM, and had no effect on stimulation by IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF)-alpha or fMet-Leu-Phe. The peptides were rapidly broken down in mouse plasma through cleavage of a single chain of the dimer. However, this breakdown did not correlate with loss of biological activity, indicating that the asymmetric peptide fragment retains full receptor binding capacity. The activity of AF18748 disappeared rapidly from the blood following intravenous injection into mice. Coupling of polyethylene glycol to the N-terminus of AF18748 resulted in a moderate loss in biological potency (IC(50)30 nM), but the resulting conjugate persisted in the circulation for more than 8 h after injection. Despite its high potency at the human IL-5 receptor, AF18748 was unable to antagonise the activity of IL-5 on murine B13 cells, or on canine eosinophils, indicating that the peptide is highly specific for the human IL-5 receptor.

Birthweights and growth of infants in five Aboriginal communities.

OBJECTIVES: To improve, by culturally appropriate means, birthweights and growth of children up to three years of age over 14 months in five Aboriginal communities in north-western Australia. METHODS: Frequent individual nutritional assessment of infants and children with counselling of mothers and carers and of pregnant women and the introduction of the Aboriginal-controlled Strong Women, Strong Babies, Strong Culture maternal support program. Outcomes compared with those in the same communities for the five years preceding intervention. RESULTS: By international standards, pre-intervention birthweights of full-term infants (37-42 weeks) were only moderately depressed and recovered to exceed standard weight-for-age within two weeks of birth. Growth of full-term infants slowed abruptly after six months. Prevalence and duration of breastfeeding were very high. Prevailing low average birthweight was chiefly attributable to a prevalence of pre-term birth approaching 20%. Intervention was not accompanied by any change in full-term birth weight but was associated with increased weight gain after six months. From 12 to 36 months growth rose by 30 g per month (p = 0.001). Average birthweights of pre-term infants were < 2,500 g and average weight-for-age did not improve during intervention. CONCLUSIONS: Both low birthweight and a disproportionate part of intransigent failure to grow by Aboriginal infants were associated with pre-term birth. Depressed average growth of full-term infants appeared to respond to nutritional counselling accompanied by a community support program. IMPLICATIONS: Investigation of the causes of the exceptionally high rate of Aboriginal pre-term birth in the region is urgently required.

A potent dimeric peptide antagonist of interleukin-5 that binds two interleukin-5 receptor alpha chains.

Two series of peptides that specifically bind to the extracellular domain of the alpha chain of the human interleukin-5 receptor (IL-5Ralpha), but share no primary sequence homology to IL-5, were identified from libraries of random recombinant peptides. Affinity maturation procedures generated a 19-aa peptide that binds to the IL-5 receptor alpha/beta heterodimer complex with an affinity equal to that of IL-5 and is a potent and specific antagonist of IL-5 activity in a human eosinophil adhesion assay. The active form of the peptide is a disulfide-crosslinked dimer that forms spontaneously in solution. Gel filtration analysis, receptor-binding studies, and analytical ultracentrifugation reveal that the dimeric peptide binds simultaneously to two receptor alpha chains in solution. Furthermore, the dimer peptide, but not IL-5, can activate a chimeric receptor consisting of the IL-5Ralpha extracellular domain fused to the intracellular domain of the epidermal growth factor receptor, thus demonstrating that the peptide also promotes receptor dimerization in a cellular context. The functional antagonism produced by the bivalent interaction of the dimeric peptide with two IL-5R alpha chains represents a distinctive mechanism for the antagonism of cytokines that use heteromeric receptors.

Primary care: past and future.

There is anecdotal evidence of a crisis in the recruitment and retention of general practitioners nationwide and particularly in inner cities. The relationship between quality of service and single-handed or group practice is uncertain and confounded by other aspects of practice structure and populations. The review examines the factors that influence doctors to enter and remain in general practice. It explores whether initiatives designed to address problems of recruitment and retention have been evaluated in the past and suggests how could they inform current initiatives.

Shared care for high-dependency patients: mental illness, neurological disorders and terminal care--a review.

Changes in the structure of health services in the UK have increased the need to identify and formalize shared responsibilities between primary and secondary care for patients with chronic conditions. There are well-established schemes for the management of patients with some chronic diseases but very little for other high-dependency groups. This review examines the extent of systematic and shared care for some of the less well served groups: these are mental illness, neurological disorders and terminal care. Examples of good practice are highlighted.

Name that tune: identifying popular recordings from brief excerpts.

We tested listeners' ability to identify brief excerpts from popular recordings. Listeners were required to match 200- or 100-msec excerpts with the song titles and artists. Performance was well above chance levels for 200-msec excerpts and poorer but still better than chance for 100-msec excerpts. Performance fell to chance levels when dynamic (time-varying) information was disrupted by playing the 100-msec excerpts backward and when high-frequency information was omitted from the 100-msec excerpts; performance was unaffected by the removal of low-frequency information. In sum, successful identification required the presence of dynamic, high-frequency spectral information.

Staphylococcus hominis subsp. novobiosepticus subsp. nov., a novel trehalose- and N-acetyl-D-glucosamine-negative, novobiocin- and multiple-antibiotic-resistant subspecies isolated from human blood cultures.

A new subspecies, Staphylococcus hominis subsp. novobiosepticus, isolated from human blood cultures, a wound, a breast abscess and a catheter tip, is described on the basis of a study of 26 strains isolated between 1989 and 1996. DNA-DNA reassociation reactions, conducted under stringent conditions, and macrorestriction pattern analysis demonstrated that these strains are closely related to previously characterized S. hominis strains isolated from human skin and clinical specimens, but are significantly divergent. S. hominis subsp. novobiosepticus can be distinguished from S. hominis (now named S. hominis subsp. hominis) by its combined characteristics of novobiocin resistance and failure to produce acid aerobically from D-trehalose and N-acetyl-D-glucosamine. Furthermore, all 26 strains of the new subspecies are resistant to nalidixic acid, penicillin G, oxacillin, kanamycin and streptomycin, and were either resistant or had intermediate resistance to methicillin and gentamicin. Most strains were also resistant to erythromycin, clindamycin, chloramphenicol, trimethoprim/sulfamethoxazole and ciprofloxacin. Based on a comparison of the sequences of a 1001 bp mecA amplification product from reference methicillin-resistant staphylococci, the mecA gene present in S. hominis subsp. novobiosepticus was identified as homologue A, commonly found in S. aureus and many coagulase-negative staphylococcal species. The type strain of S. hominis subsp. novobiosepticus is ATCC 700236T. Descriptions of S. hominis subsp. novobiosepticus subsp. nov and S. hominis subsp. hominis are given and the description of S. hominis is emended.

Clinical importance of identifying coagulase-negative staphylococci isolated from blood cultures: evaluation of MicroScan Rapid and Dried Overnight Gram-Positive panels versus a conventional reference method.

We evaluated the clinical usefulness of species identification of blood isolates of coagulase-negative staphylococci as a predictor of the clinical significance of the isolates. In addition, we compared results of species identification obtained with MicroScan Rapid Gram-Positive Identification panels and Dried Overnight (Conventional) Gram-Positive Identification panels with those obtained by a tube reference method. Two hundred eighty-five blood isolates were tested, including 92 judged to represent true bacteremia and 193 judged to represent contamination. The most common species detected were Staphylococcus epidermidis, Staphylococcus hominis, and Staphylococcus haemolyticus. These three species accounted for nearly 98% of the clinically significant isolates and 89% of the contaminants. The isolation of other species almost always represented contamination. However, identification of the three most common species did not help distinguish pathogens from contaminants. Both the Rapid and the Dried Overnight Gram-Positive panels identified S. epidermidis strains accurately, but the panels performed less well for the other species. Analysis revealed that S. hominis was frequently misidentified due to the presence of a previously unknown subspecies. Based on the initial results, revised investigational Dried Overnight Gram-Positive Identification panels (CPID-2) were prepared and tested. The CPID-2 panels identified 85 to 95% of S. epidermidis strains, 76 to 86% of S. hominis strains, and 88 to 92% of S. haemolyticus strains with high probability (>85%) and, overall, represented a significant improvement over the other panels for identification of these staphylococcal species.