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In this work, the design and execution of an experiment with the goal of demonstrating control over the evolution of a copper jet is described. Simulations show that when using simple multi-material buffers placed between a copper target with a conical cavity and a cylinder of high-explosive, a variety of jetting behaviors occur based on material placement, including both jet velocity augmentation and mitigation. A parameter sweep was performed to determine optimal buffer designs in two configurations. Experiments using the optimal buffer designs verified the effectiveness of the buffers at altering jet velocities. Similar trends were shown between the experimental results and the modeling.

In 2014, the Australian Government established the Teacher Education Ministerial Advisory Group (TEMAG) to advise on how teacher education programmes could ensure new teachers were adequately prepared for the classroom. Following this, the Australian Government endorsed a key recommendation of the TEMAG Action Now: Classroom Ready Teachers report, the inclusion of specialisations in primary Initial Teacher Education (ITE). This research was conducted at an Australian public university that, in 2016, had embedded specialisations in a revised primary teacher programme structure and was one of the first ITE institutions in Australia to graduate primary teachers with a specialisation. Using a mixed-methods case study design with convenience sampling, this study sought to investigate these primary graduates’ perceptions of undertaking a specialisation in relation to the development of content knowledge and pedagogical knowledge in the specialist area, as well as perceived employment advantages. This research took place over 4 years with participants having completed a Bachelor of Education (Primary) at least three months prior to participating. The participants reported benefits to having completed a primary specialisation but expressed concerns about their preparedness to teach their specialisation and whether it would result in any advantages for employment. Recommendations from the participants included teaching practice in their area of specialisation, consideration of specialist skills and changing the timetabling of the specialisation in the programme. Ultimately, there is a need for ongoing research in this area to determine the extent to which primary specialisations deliver the intended outcomes and impacts at both the policy driver level and the university level.

Diabetic embryopathy has been linked to congenital athymia (CA), particularly in non-DiGeorge syndromeinfants born to diabetic mothers with a genetically undefined SCID-like immunophenotype. Diagnosing CA is crucial to ensure patients receive curative treatment with cultured thymus tissue implantation (CTTI).

Recipients of autologous haemopoietic stem-cell transplants (auto-HSCT) have an increased risk of herpes zoster and herpes zoster-related complications. The aim of this study was to establish the efficacy and safety of an inactivated varicella zoster vaccine for the prevention of herpes zoster after auto-HSCT.

BACKGROUNDStatewide interventions are critical to meeting the goals of the National HIV/AIDS Strategy in this country. In 2012, the North Carolina Division of Public Health developed the North Carolina State Bridge Counselor program to improve linkage to and reengagement in care for newly diagnosed persons and persons living with HIV who were out-of-care.METHODSWe reviewed the planning process for the North Carolina State Bridge Counselor program, which involved a review of existing strengths-based counseling models for persons living with HIV, implementation of these models, and communication strategies with other providers. State bridge counselor responsibilities were delineated from the role of disease intervention specialists while retaining the fieldwork capability of disease intervention specialists to conduct outreach and provide services for persons living with HIV throughout the state.RESULTSProgram implementation required extensive planning with stakeholders, incorporation of strengths-based counseling models, development of performance standards, and utilization of CAREWare, an HIV care software program to document referrals and data-sharing between state bridge counselors and clinics. By the end of 2014, state bridge counselor services were provided to approximately 60 of the 400 persons living with HIV (15%) who are diagnosed each quarter in North Carolina, with increasing utilization of the program.LIMITATIONSWe assessed the development of this intervention specific to the North Carolina Division of Public Health, which may limit its generalizability. However, the State Bridge Counselor program was implemented in both urban and rural areas throughout the state, which increases its applicability to different public health programs throughout the country.CONCLUSIONWe demonstrated that a statewide State Bridge Counselor program for linkage and reengagement activities can be implemented by leveraging existing infrastructures, electronic medical records, HIV care networks, and fieldwork activities.

Single-agent high-dose melphalan (HDM, 200 mg/m2) has been the most commonly used conditioning regimen prior to autologous stem cell transplant, since its introduction in 1992. We used a more aggressive alkylator-based conditioning regimen in an attempt to overcome early relapse and combat drug resistance. We present a retrospective comparison and long-term follow-up of newly diagnosed patients with multiple myeloma (MM) treated with induction followed by either high-dose carmustine (BCNU) and HDM, or HDM alone, both followed by autologous stem cell transplant (ASCT). Between 1997 and 2002, 104 patients were treated with BCNU/HDM; from 2001 to 2008, 103 patients were treated with HDM alone. Median follow-up of survivors was 78 and 68 months for the BCNU/HDM and HDM groups, respectively. The median PFS was significantly increased with the BCNU/HDM regimen (40.4 vs 20.5 months, P<0.001). Median overall survival was increased with the BCNU/HDM regimen when compared with HDM alone (88.4 vs 67.2 months, P=0.07), but the difference was not statistically significant. Transplant-related mortality was similar in both groups (2.9% with BCNU and HDM vs 3.9% with HDM alone). Our findings suggest that the BCNU/HDM preparative regimen should be investigated further and potentially compared in a prospective randomized manner with HDM alone.

ABSTRACTWe evaluated the investigational use only (IUO) version of the rapid Verigene Gram-negative blood culture test (BC-GN), a microarray that detects 9 genus/species targets (Acinetobacterspp., Citrobacterspp., Enterobacterspp., Escherichia coli/Shigellaspp., Klebsiella oxytoca, Klebsiella pneumoniae, Proteusspp., Pseudomonas aeruginosa, and Serratia marcescens) and 6 antimicrobial resistance determinants (blaCTX-M, blaKPC, blaNDM, blaVIM, blaIMP, and blaOXA) directly from positive blood cultures. BC-GN was performed on positive BacT/Alert Pediatric FAN and Bactec Peds Plus blood cultures with Gram-negative organisms at two tertiary pediatric centers. Vitek MS (bioMérieux, Durham, NC) was used to assign gold standard organism identification. The Check MDR CT-102 microarray (Check Points B.V., Wageningen, Netherlands) was used as an alternative method for detecting resistance determinants. In total, 104 organisms were isolated from 97 clinical blood cultures. BC-GN correctly detected 26/26 cultures with Acinetobacterspp., P. aeruginosa, and S. marcescens, 5/6 with Citrobacterspp., 13/14 with Enterobacterspp., 23/24 with E. coli, 2/3 with K. oxytoca, 16/17 with K. pneumoniae, and 0/1 with Proteusspp. BC-GN appropriately reported negative BC-GN results in 8/13 blood cultures that grew organisms that were not represented on the microarray but failed to detect targets in 3/5 cultures that grew multiple Gram-negative organisms. BC-GN detected 5/5 and 1/1 clinical blood cultures with blaCTX-Mand blaVIM. All 6 results were corroborated by Check MDR CT-102 microarray testing. The Verigene BC-GN test has the potential to expedite therapeutic decision making in pediatric patients with Gram-negative bacteremia. Sensitivity was satisfactory but may be suboptimal in mixed Gram-negative blood cultures.

ABSTRACTHere, we compare the sensitivities and times to detection (TTD) of BacT/Alert Pediatric FAN (PF) and Bactec Peds Plus blood culture bottles. Test bottles were inoculated with 2 ml of banked whole blood, 1-ml aliquots of antibiotic suspension, and organisms diluted to simulate a bacteremia level of 10 to 100 CFU/ml. The control bottles were inoculated with 3 ml of banked blood and organism suspensions only. The organism-drug combinations were Staphylococcus epidermidisand vancomycin, methicillin-resistant Staphylococcus aureusand vancomycin, Streptococcus pneumoniae, vancomycin, and ceftriaxone, Streptococcus agalactiae, ampicillin, and cefotaxime, Escherichia coli, cefotaxime, and cefepime, Pseudomonas aeruginosa, piperacillin-tazobactam, cefepime, and gentamicin, Neisseria meningitidisand ceftriaxone, and Haemophilus influenzaeand ceftriaxone. The control and test bottle combinations were tested in duplicate. The bottles were incubated for 5 days; 32 control and 104 test bottles were incubated. Overall, the bacterial recovery rates for the PF and Peds Plus bottles were 37% and 62%, 94% and 100% in the controls, 19% and 50% in the test bottles, and 33% and 92% in the bottles with vancomycin, respectively. No bacteria were recovered from the bottles with S. pneumoniae, S. agalactiae, E. coli, N. meningitidis, or H. influenzaein combination with cefotaxime or ceftriaxone. The Peds Plus system detected P. aeruginosain bottles with cefepime and piperacillin-tazobactam, but the PF system recovered bacteria only in bottles with trough levels of piperacillin-tazobactam. The mean TTD were shorter in the Peds Plus system controls (14.2 versus 18.0 h; P= 0.001) and the test bottles (14.3 versus 17.8 h; P= 0.008) than in the PF bottles. Overall, we demonstrated superior sensitivity, TTD, and antibiotic neutralization in the Bactec Peds Plus system compared to those in the Pediatric FAN system.

ABSTRACTAssays that expedite the reporting of organism identification and antibiotic susceptibility status in positive blood cultures can fast track interventions that improve clinical outcomes. We evaluated the Verigene Gram-positive blood culture nucleic acid test (BC-GP) in two pediatric hospitals. Positive BacT/Alert Pediatric FAN blood cultures with Gram-positive organisms were tested using the BC-GP in tandem with routine laboratory procedures. To test organisms underrepresented in the clinical blood culture evaluation, blood culture bottles were spiked with diluted organism suspensions at concentrations of 10 to 100 CFU per milliliter. A total of 249 Gram-positive bacterial isolates were recovered from 242 blood cultures. The BC-GP detected Staphylococcus aureus, methicillin-susceptible S. aureus, and methicillin-resistant S. aureuswith sensitivities of 100%, 99%, and 100% and specificities of 100%, 100%, and 99.5%, respectively. The BC-GP detected Staphylococcus epidermidis, methicillin-susceptible S. epidermidis, and methicillin-resistant S. epidermidiswith sensitivities of 95%, 80%, and 96%, respectively, and 100% specificity. The BC-GP correctly identified 14/15 cases of Enterococcus faecalisand Enterococcus faeciumbacteremia and 9 cases of Streptococcus pneumoniae. It misidentified 5/15 clinical blood cultures with Streptococcus mitis/Streptococcus oralisand 1/3 blood cultures spiked with Streptococcus anginosusgroup as S. pneumoniae. The BC-GP detected a case of Streptococcus pyogenesbacteremia but failed to detect 2/3 clinical blood cultures with Streptococcus agalactiae. BC-GP's rapid accurate detection of Staphylococcusspp., E. faecium, and E. faecalisand its ability to ascertain mecA, vanA, and vanBstatus may expedite clinical decisions pertaining to optimal antibiotic use. False-positive S. pneumoniaeresults may warrant reporting of only “Streptococcusspp.” when this organism is reported by the BC-GP.

To evaluate the efficacy and tolerability of lubiprostone (Amitiza) for constipation in Parkinson disease (PD) in a double-blind, randomized, controlled study.

Nonmotor symptoms (sleep dysfunction, sensory symptoms, autonomic dysfunction, mood disorders, and cognitive abnormalities) in Parkinson disease (PD) are a major cause of morbidity, yet are often underrecognized. This evidence-based practice parameter evaluates treatment options for the nonmotor symptoms of PD. Articles pertaining to cognitive and mood dysfunction in PD, as well as treatment of sialorrhea with botulinum toxin, were previously reviewed as part of American Academy of Neurology practice parameters and were not included here.

Previous studies showed that absence of chemokine receptor Cxcr3 or its blockade prolong mouse cardiac allograft survival. We evaluated the effect of the CXCR3 receptor antagonist MRL-957 on cardiac allograft survival, and also examined the impact of anti-CXCR3 mAb in human CXCR3 knock-in mice. We found only a moderate increase in graft survival (10.5 and 16.6 days, p < 0.05) using either the antagonist or the antibody, respectively, compared to control (8.7 days). We re-evaluated cardiac allograft survival with two different lines of Cxcr3?-mice. Interestingly, in our hands, neither of the independently derived Cxcr3?-lines showed remarkable prolongation, with mean graft survival of 9.5 and 10.8 days, respectively. There was no difference in the number of infiltrating mononuclear cells, expansion of splenic T cells or IFN-? production of alloreactive T cells. Mechanistically, an increased other chemokine receptor fraction in the graft infiltrating CD8 T cells in Cxcr3?-recipients compared to wild-type recipients suggested compensatory T-cell trafficking in the absence of Cxcr3. We conclude Cxcr3 may contribute to, but does not govern, leukocyte trafficking in this transplant model.

This cross-sectional study investigated the prevalence of HIV testing amongst South African high school students, their perceptions about HIV testing, and the influence of HIV testing on their sexual behaviour. Grade 10 students at 28 high schools completed a questionnaire based on the I-Change Model. Of 1,192 students, 57 (4.8%) had been tested for HIV. More tested students knew a person with HIV/AIDS (p<0.005), knew other people who had been tested (p<0.005), perceived support from family (p<0.005) and friends (p=0.003), and reported self-efficacy and further intentions to be tested (p<0.005). HIV counselling and testing can promote prevention messages to reduce the prevalence of HIV infection amongst HIVseronegative people, and decrease transmission amongst those HIV-seropositive. Early diagnosis and care can improve outcomes for HIV/AIDS. Encouraging HIV testing among school students may contribute to a reduction in HIV incidence and persuade students to reduce risky sexual behaviour.

Background. Like other health care workers, dental professionals are at risk of developing allergic contact dermatitis, or ACD, after exposure to allergenic chemicals. Common allergens include antimicrobials, preservatives, rubber additives and methacrylates.Case Description. The authors describe an orthodontic assistant with severe skin disease, whose symptoms included redness, cracking and bleeding that persisted for 10 years. The patient had previously received an incomplete diagnosis. After performing patch testing, assessing symptoms and evaluating the patient's medical history, the authors diagnosed ACD resulting from exposure to several dental allergens. The patient received appropriate treatment and counseling to better manage her allergies; this resulted in resolution of all symptoms and averted permanent occupational disability.Clinical Implications. Not all skin reactions are related to gloves or natural rubber latex. Dental professionals should be aware of common chemical allergens, symptoms of ACD and the appropriate treatment of occupational skin disease. [ABSTRACT FROM AUTHOR]

The recent identification of TGFBR2 mutations in Marfan syndrome II (MFSII) [Mizuguchi et al. (2004); Nat Genet 36:855–860] and of TGFBR1 and TGFBR2 mutations in Loeys–Dietz aortic aneurysm syndrome (LDS) [Loeys et al. (2005); Nat Genet 37:275–281] [OMIM 609192] has provided direct evidence of abnormal signaling in transforming growth factors β (TGF‐β) in the pathogenesis of Marfan syndrome (MFS). In light of this, we describe the phenotypes and genotypes of five individuals. Patient 1 had MFS and abnormal cranial dura. Patient 2 had severe early onset MFS and an abnormal skull. Patients 3 and 4 had probable Furlong syndrome (FS). Patient 5 had marfanoid (MD) features, mental retardation (MR), and a deletion of chromosome 15q21.1q21.3. All patients had a condition within the MFS, MD‐craniosynostosis (CS) or MD‐MR spectrum. The names of these entities may become redundant, and instead, come to be considered within the spectrum of TGF‐β signaling pathway disorders. Two recurrent heterozygous FBN1 mutations were found in Patients 1 and 2, and an identical novel heterozygous de novo TGFBR1 mutation was found in Patients 3 and 4, in whom altered fibrillin‐1 processing was demonstrated previously [Milewicz et al. (2000); Am J Hum Genet 67:279]. A heterozygous FBN1 deletion was found in Patient 5. These findings support the notion that perturbation of extracellular matrix homeostasis and/or remodeling caused by abnormal TGF‐β signaling is the core pathogenetic mechanism in MFS and related entities including the MD‐CS syndromes. © 2006 Wiley‐Liss, Inc.

A wheeled walking aid with an embedded controlled braking system is described. The frame of the prototype is based on combining features of standard available wheeled walking aids. A braking scheme has been designed using hydraulic disc brakes to facilitate accurate and sensitive controlled stopping of the walker by the user, and if called upon, by automatic action. Braking force is modulated via a linear actuating stepping motor. A microcontroller is used for control of both stepper movement and for supervisory control. An encoder is used to supervise walker movement in terms of time, distance and speed.

Research within the health and welfare program of the Cooperative Research Centre for Cattle and Beef Quality has delivered important improvements to the Australian cattle industry. Vaccines to assist with the control of bovine respiratory disease were developed and commercialised from Australian isolates of Mannheimia haemolytica and pestivirus (mucosal disease). Our understanding of the benefits of weaning cattle by confinement and hand feeding in yards (yard weaning) has been consolidated, and yard weaning has been adopted as ?best practice' for cattle production in the temperate zones of Australia. The importance of good temperament for improved growth rates and reduced morbidity during feedlot finishing, and for adaptation to stressors such as road transport, has been demonstrated. In response to this knowledge, industry is increasingly measuring flight time for use in breeding programs and feedlot management. The risk to meat quality of stressors such as mixing unfamiliar cattle in the weeks preceding slaughter or acute stress in the last 15 min before slaughter has been described. Adoption of these findings through Quality Assurance schemes will assist in assurance for the community and for export markets of the welfare standards of the Australian cattle and beef industry. This review provides details of the experiments that led to these achievements and to some improved understandings of temperament and behaviour of beef cattle.

An investigation was undertaken in 2004 by the KwaZulu-Natal Income Dynamics Study (KIDS) which provided an opportunity to assess the nutritional status of preschool children (6 months to less than 7 years) a decade after democracy. During the past decade, Government has initiated a range of nutritional programmes to improve children’s health and nutritional status. The KIDS survey investigated over 1200 households selected via census enumerator areas throughout the province. Of the 1146 children, 574 (50.1%) were boys and 572 (49.9%) girls, with amean age of 47.0 (SD 22.6) months for boys and 44.8 (SD 22.2) months for girls. There were statistically significant gender differences for height with boys taller than girls (p=0.002). Mean weight of boys and girls was similar (p=0.87), as was BMI (p=0.17). Overall, 1.6% of children were wasted, 7.5% were underweight and 19.8% were stunted; boys were significantly more wasted than girls (p=0.007) and more underweight (p=0.002), but not stunted (p=0.2). Chi-square tests of trend over age group found a significant decrease in wasting from 1-6 years of age (p=0.03), but not for underweight (p=0.75). There was a significant decrease in overweight (p<0.0005) and in stunting (p=0.006) from 1-6 years. The persistence of an unacceptably high prevalence of under-nutrition constitutes a public health problem amongst KwaZulu-Natal children. The key finding of this study was that the prevalence of stunting among preschool children shows minimal change when compared with the 1994 SAVACG study: wasting of 0.79% (1994) vs 1.6% (2004), overweight of 4.2% (1994) vs 7.5% (2004) and stunting of 15.6%, (1994) vs 19.6% (2004). In addition to nutritional programmes, other multi-factorial interventions targeting factors such as poverty, HIV/AIDS, and concomitant infections, as reflected in the UNICEF conceptual framework, are required to address persistent stunting among young children.

Essential tremor (ET) is one of the most common tremor disorders in adults and is characterized by kinetic and postural tremor. To develop this practice parameter, the authors reviewed available evidence regarding initiation of pharmacologic and surgical therapies, duration of their effect, their relative benefits and risks, and the strength of evidence supporting their use.

To identify a haplotype influencing onset age for Parkinson’s disease (PD) in the PARK3region on chromosome 2p13.

Objectives. Systemic lupus erythematosus (SLE) is a polygenic disorder of dysregulated inflammation. Numerous specific candidate genes have been identified and most relate to the handling of immune complexes or antigen presentation. This is consistent with the classic finding of immune complex deposition in affected end organs. We wished to examine combinatorial effects of polymorphic variants of genes involved in immune complex clearance in susceptibility to lupus.Methods. This study examined the occurrence of polymorphisms in genes which encode proteins known to be involved in immune complex handling and clearance. Each polymorphic variant of a complement protein (C2, mannose binding protein and C4), complement receptor (CR1) or Fc receptor (FcΓRIIA and FcΓRIIIA) gene is known to affect function adversely. One hundred and sixty SLE patients and 212 control subjects were genotyped using polymerase chain reaction methods.Results. We found an increasing association of SLE with increasing numbers of gene defects. Combinations of severe defects in FcΓRIIA and FcΓRIIIA were particularly deleterious for both African American and Caucasian patients, even though only one defective variant was individually statistically significantly associated with SLE.Conclusions. The results of the study suggest that genes may interact in ways that either synergize or modify the effect of a single genetic effect and imply that association studies must be interpreted within the genetic background of the populations.

Objective. Chronic graft‐versus‐host disease (GVHD) after haematopoietic stem cell transplantation (HSCT) has similarities to some idiopathic autoimmune diseases, including polymyositis. To investigate the relationship between chronic GVHD and idiopathic myositis we conducted a detailed analysis of all cases of myositis occurring in a large series of HSCT patients.Methods. We conducted a retrospective chart review of all cases of myositis that developed in 7161 patients who underwent HSCT at the Fred Hutchinson Cancer Research Center between 1969 and 1999.Results. Among 1859 individuals who developed chronic GVHD, 12 developed myositis. No patients developed myositis without chronic GVHD. Myositis was first identified between 7 and 55 months after transplantation. In histopathology, electromyography, laboratory values and response to immunosuppressive therapy, the cases resembled idiopathic polymyositis. Autoantibodies were found in eight cases.Conclusions. Myositis in the chronic GVHD population occurred with an incidence higher than expected by chance, suggesting that muscle may be a target tissue for chronic GVHD. Recent studies have implicated allogeneic cells persisting after maternal–fetal cell transfer in selected autoimmune diseases, including myositis. This report lends support to the possibility that both idiopathic myositis and chronic GVHD‐related myositis could involve allo‐autoimmune responses.

The mechanisms that specify precisely where mammalian kinetochores form within arrays of centromeric heterochromatin remain largely unknown. Localization of CENP-A exclusively beneath kinetochore plates suggests that this distinctive histone might direct kinetochore formation by altering the structure of heterochromatin within a sub-region of the centromere. To test this hypothesis, we experimentally mistargeted CENP-A to non-centromeric regions of chromatin and determined whether other centromere-kinetochore components were recruited. CENP-A-containing non-centromeric chromatin assembles a subset of centromere-kinetochore components, including CENP-C, hSMC1, and HZwint-1 by a mechanism that requires the unique CENP-A N-terminal tail. The sequence-specific DNA-binding protein CENP-B and the microtubule-associated proteins CENP-E and HZW10 were not recruited, and neocentromeric activity was not detected. Experimental mistargeting of CENP-A to inactive centromeres or to acentric double-minute chromosomes was also not sufficient to assemble complete kinetochore activity. The recruitment of centromere-kinetochore proteins to chromatin appears to be a unique function of CENP-A, as the mistargeting of other components was not sufficient for assembly of the same complex. Our results indicate at least two distinct steps in kinetochore assembly: (1) precise targeting of CENP-A, which is sufficient to assemble components of a centromere-prekinetochore scaffold; and (2) targeting of kinetochore microtubule-associated proteins by an additional mechanism present only at active centromeres.

After DNA replication, cells condense their chromosomes in order to segregate them during mitosis. The condensation process as well as subsequent segregation requires phosphorylation of histone H3 at serine 10. Histone H3 phosphorylation initiates during G2 in pericentric foci prior to H3 phosphorylation in the chromosome arms. Centromere protein A (CENP-A), a histone H3-like protein found uniquely at centromeres, contains a sequence motif similar to that around H3 Ser10, suggesting that CENP-A phosphorylation might be linked to pericentric initiation of histone H3 phosphorylation. To test this hypothesis, we generated peptide antibodies against the putative phosphorylation site of CENP-A. ELISA, western blot and immunocytochemical analyses show that CENP-A is phosphorylated at the shared motif. Simultaneous co-detection demonstrates that phosphorylation of CENP-A and histone H3 are separate events in G2/M. CENP-A phosphorylation occurs after both pericentric initiation and genome-wide stages of histone H3 phosphorylation. Quantitative immunocytochemistry reveals that CENP-A phosphorylation begins in prophase and reaches maximal levels in prometaphase. CENP-A phosphoepitope reactivity is lost during anaphase and becomes undetectable in telophase cells. Duplication of prekinetochores, detected as the doubling of CENP-A foci, occurs prior to complete histone H3 phosphorylation in G2. Mitotic phosphorylation of histone H3-family proteins shows tight spatial and temporal control, occurring in three phases: (1) pericentric H3 phosphorylation, (2) chromosome arm H3 phosphorylation and (3) CENP-A phosphorylation at kinetochores. These observations reveal new cytological landmarks characteristic of G2 progression.