Development of a parent-reported questionnaire evaluating upper limb activity limitation in children with cerebral palsy.

BACKGROUND AND PURPOSE: Upper limb activity measures for children with cerebral palsy have a number of limitations, for example, lack of validity and poor responsiveness. To overcome these limitations, we developed the Children's Arm Rehabilitation Measure (ChARM), a parent-reported questionnaire validated for children with cerebral palsy aged 5-16 years. This paper describes both the development of the ChARM items and response categories and its psychometric testing and further refinement using the Rasch measurement model. METHODS: To generate valid items for the ChARM, we collected goals of therapy specifically developed by therapists, children with cerebral palsy, and their parents for improving activity limitation of the upper limb. The activities, which were the focus of these goals, formed the basis for the items. Therapists typically break an activity into natural stages for the purpose of improving activity performance, and these natural orders of achievement formed each item's response options. Items underwent face validity testing with health care professionals, parents of children with cerebral palsy, academics, and lay persons. A Rasch analysis was performed on ChARM questionnaires completed by the parents of 170 children with cerebral palsy from 12 hospital paediatric services. The ChARM was amended, and the procedure repeated on 148 ChARMs (from children's mean age: 10 years and 1 month; range: 4 years and 8 months to 16 years and 11 months; 85 males; Manual Ability Classification System Levels I = 9, II = 26, III = 48, IV = 45, and V = 18). RESULTS: The final 19-item unidimensional questionnaire displayed fit to the Rasch model (chi-square p = .18), excellent reliability (person separation index = 0.95, α = 0.95), and no floor or ceiling effects. Items showed no response bias for gender, distribution of impairment, age, or learning disability. DISCUSSION: The ChARM is a psychometrically sound measure of upper limb activity validated for children with cerebral palsy aged 5-16 years. The ChARM is freely available for use to clinicians and nonprofit organisations.

Epizootics of Streptococcus agalactiae infection in captive rays from Queensland, Australia.

The aim of this study was to describe two epizootics of high mortalities from infection with Streptococcus agalactiae, occurring in captive rays held in a marine display aquarium in south-east Queensland, Australia, in 2009 and 2010. Five different species of rays were affected, including mangrove whiprays (Himantura granulata), estuary rays (Dasyatis fluviorum), eastern shovelnose rays (Aptychotrema rostrata), white-spotted eagle rays (Aetobatus narinari) and blue-spotted mask rays (Neotrygon kuhlii). This report describes the history of both epizootics including collection, quarantine and husbandry of rays, the disease epizootics, clinico-pathological features of the disease, antimicrobial therapy, autogenous vaccine production, and laboratory studies including clinical and histopathology, bacteriology, PCR, molecular serotyping and sequencing of the bacterium S. agalactiae.

Dietary Diversity on the Swahili Coast: The Fauna from Two Zanzibar Trading Locales.

Occupants of coastal and island eastern Africa-now known as the 'Swahili coast'-were involved in long-distance trade with the Indian Ocean world during the later first millennium CE. Such exchanges may be traced via the appearance of non-native animals in the archaeofaunal record; additionally, this record reveals daily culinary practises of the members of trading communities and can thus shed light on subsistence technologies and social organisation. Yet despite the potential contributions of faunal data to Swahili coast archaeology, few detailed zooarchaeological studies have been conducted. Here, we present an analysis of faunal remains from new excavations at two coastal Zanzibar trading locales: the small settlement of Fukuchani in the north-west and the larger town of Unguja Ukuu in the south-west. The occurrences of non-native fauna at these sites-Asian black rat (Rattus rattus) and domestic chicken (Gallus gallus), as well as domestic cat (Felis catus)-are among the earliest in eastern Africa. The sites contrast with one another in their emphases on wild and domestic fauna: Fukuchani's inhabitants were economically and socially engaged with the wild terrestrial realm, evidenced not only through diet but also through the burial of a cache of wild bovid metatarsals. In contrast, the town of Unguja Ukuu had a domestic economy reliant on caprine herding, alongside more limited chicken keeping, although hunting or trapping of wild fauna also played an important role. Occupants of both sites were focused on a diversity of near-shore marine resources, with little or no evidence for the kind of venturing into deeper waters that would have required investment in new technologies. Comparisons with contemporaneous sites suggest that some of the patterns at Fukuchani and Unguja Ukuu are not replicated elsewhere. This diversity in early Swahili coast foodways is essential to discussions of the agents engaged in long-distance maritime trade.

mTORC2 signalling regulates M2 macrophage differentiation in response to helminth infection and adaptive thermogenesis.

Alternatively activated macrophages (M2) have an important function in innate immune responses to parasitic helminths, and emerging evidence also indicates these cells are regulators of systemic metabolism. Here we show a critical role for mTORC2 signalling in the generation of M2 macrophages. Abrogation of mTORC2 signalling in macrophages by selective conditional deletion of the adaptor molecule Rictor inhibits the generation of M2 macrophages while leaving the generation of classically activated macrophages (M1) intact. Selective deletion of Rictor in macrophages prevents M2 differentiation and clearance of a parasitic helminth infection in mice, and also abrogates the ability of mice to regulate brown fat and maintain core body temperature. Our findings define a role for mTORC2 in macrophages in integrating signals from the immune microenvironment to promote innate type 2 immunity, and also to integrate systemic metabolic and thermogenic responses.

Direct Measurement of the Density Matrix of a Quantum System.

One drawback of conventional quantum state tomography is that it does not readily provide access to single density matrix elements since it requires a global reconstruction. Here, we experimentally demonstrate a scheme that can be used to directly measure individual density matrix elements of general quantum states. The scheme relies on measuring a sequence of three observables, each complementary to the last. The first two measurements are made weak to minimize the disturbance they cause to the state, while the final measurement is strong. We perform this joint measurement on polarized photons in pure and mixed states to directly measure their density matrix. The weak measurements are achieved using two walk-off crystals, each inducing a polarization-dependent spatial shift that couples the spatial and polarization degrees of freedom of the photons. This direct measurement method provides an operational meaning to the density matrix and promises to be especially useful for large dimensional states.

The Leeds Assessment of Neuropathic Symptoms and Signs Scale (LANSS) is not an adequate outcome measure of pressure ulcer-related neuropathic pain.

BACKGROUND: Few pain assessment scales have been used in pressure ulcer (PU) research and none developed or validated for people with PUs. We examined the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale to determine its utility as an outcome measure for people with pressure area-related pain. METHODS: Leeds Assessment of Neuropathic Symptoms and Signs data from 728 participants underwent psychometric analyses: traditional tests for data quality, scaling assumptions, reliability and validity and a Rasch analysis including tests of fit, spread and targeting of item locations, response dependency, person separation index (reliability) and differential item functioning. RESULTS: Our findings offer support for a unidimensional scale; confirmatory factor analysis indicated a non-significant chi-square test of model fit [(df = 14) 23.48, p = 0.053]. However, some misfit was identified at the overall scale and individual item levels, and internal construct validity of the LANSS as an outcome measure for neuropathic pain in people with pressure area-related pain was not supported; low to moderate item-total correlations [Chi Square (df = 28) 55.546, p = 0.002] and inter-item correlations (mean 0.117 and range from 0.063 to 0.415); and low Cronbach's alpha (0.549) and Person Separation Index (0.334). CONCLUSIONS: Requirements for reliable and valid measurement do not support the use of the LANSS as an outcome measure in people with PUs at the individual level or as a generalized measurement scale of neuropathic pain across ulcer severity groups. Expanding the number of items to aid differentiation between neuropathic pain levels and improving scale reliability is recommended. WHAT DOES THIS STUDY ADD?: The Leeds Assessment of Neuropathic Symptoms and Signs scale (LANSS) is not suitable as an outcome measure of pressure ulcer-related neuropathic pain as it did not meet requirements for reliable and valid measurement in this population.

Social and Structural Factors Shaping High Rates of Incarceration among Sex Workers in a Canadian Setting.

In light of the emphasis on enforcement-based approaches towards sex work, and the well-known negative impacts of these approaches on women's health, safety and well-being, we conducted a study to investigate the prevalence and correlates of recent incarceration among a cohort of women sex workers in Vancouver, Canada. Data were obtained from an open prospective community cohort of female and transgender women sex workers, known as An Evaluation of Sex Workers' Health Access (AESHA). Bivariate and multivariable logistic regression analyses, using generalized estimating equations (GEE), were used to model the effect of social and structural factors on the likelihood of incarceration over the 44-month follow-up period (January 2010-August 2013). Among 720 sex workers, 62.5 % (n = 450) reported being incarcerated in their lifetime and 23.9 % (n = 172) being incarcerated at least once during the study period. Of the 172 participants, about one third (36.6 %) reported multiple episodes of incarceration. In multivariable GEE analyses, younger age (adjusted odds ratio [AOR] = 1.04 per year younger, 95 % confidence interval [CI] 1.02-1.06), being of a sexual/gender minority (AOR = 1.62, 95 % CI 1.13-2.34), heavy drinking (AOR = 1.99, 95 % CI 1.20-3.29), being born in Canada (AOR = 3.28, 95 % CI 1.26-8.53), living in unstable housing conditions (AOR = 4.32, 95 % CI 2.17-8.62), servicing clients in public spaces (versus formal sex work establishments) (AOR = 2.33, 95 % CI 1.05-5.17) and experiencing police harassment without arrest (AOR = 1.82, 95 % CI 1.35-2.45) remain independently correlated with incarceration. This prospective study found a very high prevalence and frequency of incarceration among women sex workers in Vancouver, Canada, with the most vulnerable and marginalized women at increased risk of incarceration. Given the well-known social and health harms associated with incarceration, and associations between police harassment and incarceration in this study, our findings further add to growing calls to move away from criminalized and enforcement-based approaches to sex work in Canada and globally.

Interactions between Cooccurring Lactic Acid Bacteria in Honey Bee Hives.

In contrast to the honey bee gut, which is colonized by a few characteristic bacterial clades, the hive of the honey bee is home to a diverse array of microbes, including many lactic acid bacteria (LAB). In this study, we used culture, combined with sequencing, to sample the LAB communities found across hive environments. Specifically, we sought to use network analysis to identify microbial hubs sharing nearly identical operational taxonomic units, evidence which may indicate cooccurrence of bacteria between environments. In the process, we identified interactions between noncore bacterial members (Fructobacillus and Lactobacillaceae) and honey bee-specific "core" members. Both Fructobacillus and Lactobacillaceae colonize brood cells, bee bread, and nectar and may serve the role of pioneering species, establishing an environment conducive to the inoculation by honey bee core bacteria. Coculture assays showed that these noncore bacterial members promote the growth of honey bee-specific bacterial species. Specifically, Fructobacillus by-products in spent medium supported the growth of the Firm-5 honey bee-specific clade in vitro. Metabolic characterization of Fructobacillus using carbohydrate utilization assays revealed that this strain is capable of utilizing the simple sugars fructose and glucose, as well as the complex plant carbohydrate lignin. We tested Fructobacillus for antibiotic sensitivity and found that this bacterium, which may be important for establishment of the microbiome, is sensitive to the commonly used antibiotic tetracycline. Our results point to the possible significance of "noncore" and environmental microbial community members in the modulation of honey bee microbiome dynamics and suggest that tetracycline use by beekeepers should be limited.

Neuropeptide Y receptor Y5 as an inducible pro-survival factor in neuroblastoma: implications for tumor chemoresistance.

Neuroblastoma (NB) is a pediatric tumor of neural crest origin with heterogeneous phenotypes. Although low-stage tumors carry a favorable prognosis, >50% of high-risk NB relapses after treatment with a fatal outcome. Thus developing therapies targeting refractory NB remains an unsolved clinical problem. Brain-derived neurotrophic factor (BDNF) and its TrkB receptor are known to protect NB cells from chemotherapy-induced cell death, while neuropeptide Y (NPY), acting via its Y2 receptor (Y2R), is an autocrine proliferative and angiogenic factor crucial for maintaining NB tumor growth. Here we show that in NB cells, BDNF stimulates the synthesis of NPY and induces expression of another one of its receptors, Y5R. In human NB tissues, the expression of NPY and Y5R positively correlated with the expression of BDNF and TrkB. Functionally, BDNF triggered Y5R internalization in NB cells, whereas Y5R antagonist inhibited BDNF-induced p44/42 mitogen-activated protein kinase activation and its pro-survival activity. These observations suggested TrkB-Y5R transactivation that resulted in cross-talk between their signaling pathways. Additionally, NPY and Y5R were upregulated in a BDNF-independent manner in NB cells under pro-apoptotic conditions, such as serum deprivation and chemotherapy, as well as in cell lines and tissues derived from posttreatment NB tumors. Blocking Y5R in chemoresistant NB cells rich in this receptor sensitized them to chemotherapy-induced apoptosis and inhibited their growth in vivo by augmenting cell death. In summary, the NPY/Y5R axis is an inducible survival pathway activated in NB by BDNF or cellular stress. Upon such activation, Y5R augments the pro-survival effect of BDNF via its interactions with TrkB receptor and exerts an additional BDNF-independent anti-apoptotic effect, both of which contribute to NB chemoresistance. Therefore, the NPY/Y5R pathway may become a novel therapeutic target for patients with refractory NB, thus far an incurable form of this disease.

Mg doping affects dislocation core structures in GaN.

Aberration-corrected scanning transmission electron microscopy was used to investigate the core structures of threading dislocations in undoped GaN films with both high and low dislocation densities, and in a comparable high dislocation density Mg-doped GaN film. All a-type dislocations in all samples have a 5/7-atom core structure. In contrast, most (a+c)-type dislocations in undoped GaN dissociate due to local strain variations from nearby dislocations. In contrast, Mg doping prevents (a+c)-type dislocation dissociation. Our data indicate that Mg affects dislocation cores in GaN significantly.

Masseter function and skeletal malocclusion.

The aim of this work is to review the relationship between the function of the masseter muscle and the occurrence of malocclusions. An analysis was made of the masseter muscle samples from subjects who underwent mandibular osteotomies. The size and proportion of type-II fibers (fast) decreases as facial height increases. Patients with mandibular asymmetry have more type-II fibers on the side of their deviation. The insulin-like growth factor and myostatin are expressed differently depending on the sex and fiber diameter. These differences in the distribution of fiber types and gene expression of this growth factor may be involved in long-term postoperative stability and require additional investigations. Muscle strength and bone length are two genetically determined factors in facial growth. Myosin 1H (MYOH1) is associated with prognathia in Caucasians. As future objectives, we propose to characterize genetic variations using "Genome Wide Association Studies" data and their relationships with malocclusions.

Revisiting thalidomide: fighting with caution against idiopathic pulmonary fibrosis.

Thalidomide is an infamous drug whose use by pregnant women in the middle of last century tragically resulted in serious birth defects. However, as a result of its potent immunomodulatory, anti-inflammatory and antiangiogenic properties, thalidomide may be a potential therapy in many diseases. In recent years, thalidomide has been used effectively to treat various malignancies, including multiple myeloma, myelodysplastic syndromes, renal cell cancer, glioblastoma multiforme and prostate cancer. In addition, thalidomide has also proven effective against other immune-related diseases, including erythema nodosum leprosum and sarcoidosis. Idiopathic pulmonary fibrosis (IPF) is a deadly fibrotic disease with no effective treatment options. However, there is data to suggest that thalidomide may be useful in treating the chronic, disabling cough that accompanies IPF. It remains to be seen whether the immunomodulatory and antiangiogenic properties of thalidomide will also make it a potential therapy against the clinical progression of IPF.

Computer based haemodynamic guidance system is effective and safe in management of postoperative cardiac surgery patients.

A circulatory guidance system, Navigator, was evaluated in a prospective, randomised control trial at six Australian university teaching hospitals involving 112 scheduled postoperative cardiac surgical patients with pulmonary artery catheters placed and receiving 1:1 nursing care. The guidance system was used to achieve and maintain physician-designated cardiac output and mean arterial pressure targets and compared these with standard post open-heart surgery care. The primary efficacy endpoint was the standardised unsigned error between the targeted and the actual values for cardiac output and mean arterial pressure, time averaged over the duration of cardiac output monitoring - the average standardised distance. This was 1.71 (SD=0.65) for the guidance group and 1.92 (SD=0.65) in the control group (P=0.202). Rates of postoperative atrial fibrillation, adverse events, intensive care unit and hospital length-of-stay were similar in both groups. There were no device-related adverse events. Guided haemodynamic therapy with the Navigator device was non-inferior to standard intensive care unit therapy. The study was registered with ClinicalTrials.gov Identifier NCT00468247.

Healthy lifestyle factors associated with reduced cardiometabolic risk.

Minimal data are available regarding the cumulative effects of healthy lifestyle behaviours on cardiometabolic risk. The objective of the present study was to examine a combination of healthy lifestyle behaviours associated with cardiometabolic risk reduction. The analysis was based on a cross-sectional study of 1454 participants from the population-based Lipid Research Clinic's Princeton Follow-up Study. The healthy lifestyle factors included fruit and vegetable intake ≥ 5 servings/d, meat intake ≤ 2 servings/d, never smoking, consuming 2-6 alcoholic drinks/week, television (TV) viewing time ≤ 2 h/d and moderate to vigorous physical activity ≥ 4 h/week. The combination of healthy lifestyle behaviours was strongly and negatively associated with the presence of cardiometabolic risk, as well as with a composite cardiometabolic risk score after adjustment for race, age, generation and sex. With each additional healthy lifestyle factor, cardiometabolic risk decreased by 31 % (OR 0·69; 95 % CI 0·61, 0·78). A higher healthy lifestyle score was associated with a lower prevalence of cardiometabolic risk (P for trend < 0·001). Compared with individuals having 0-1 healthy lifestyle behaviours, those with 5 or 6 healthy lifestyle behaviours had a 70 % lower prevalence of cardiometabolic risk (OR 0·30; 95 % CI 0·13, 0·67). Healthy lifestyle behaviours including sufficient fruit and vegetable intake, less meat intake, less TV viewing time, abstinence from smoking, modest alcohol intake and regular exercise are associated with reduced cardiometabolic risk.

Controlled nanometric phase transitions of phospholipid membranes by plasmonic heating of single gold nanoparticles.

The development of remotely controlled nanoscopic sources of heat is essential for investigating and manipulating temperature sensitive processes at the nanoscale. Here, we use single gold nanoparticles to rapidly deposit controlled amounts of heat in nanoscopic regions of defined size. This allows us to induce and control nanoscale reversible gel-fluid phase transitions in phospholipid membranes. We exploit the optical control over the phase transition to determine the velocity of the fluid phase front into the gel phase membrane and to guide the nanoparticles to specific locations. These results illustrate how single gold nanoparticles enable local thermodynamic investigation and manipulation on nanoscale (bio-) systems.

Focused ion beam milling and ultramicrotomy of mineralised ivory dentine for analytical transmission electron microscopy.

The use of focused ion beam (FIB) milling for preparation of sections of mineralised ivory dentine for transmission electron microscopy (TEM) is investigated. Ivory dentine is essentially composed of fibrillar type-I collagen and apatite crystals. The aim of this project is to gain a clearer understanding of the relationship between the organic and inorganic components of ivory dentine using analytical TEM, in order to utilise these analytical techniques in the context of common skeletal diseases such as osteoporosis and arthritis. TEM sections were prepared in both single and dual beam FIB instruments, using two standard lift-out techniques, in situ and ex situ. The FIB sections were systematically compared with sections prepared by ultramicrotomy, the traditional preparation route in biological systems, in terms of structural and chemical differences. A clear advantage of FIB milling over ultramicrotomy is that dehydration, embedding and section flotation can be eliminated, so that partial mineral loss due to dissolution is avoided. The characteristic banding of collagen fibrils was clearly seen in FIB milled sections without the need for any chemical staining, as is commonly employed in ultramicrotomy. The FIB milling technique was able to produce high-quality TEM sections of ivory dentine, which are suitable for further investigation using electron energy-loss spectroscopy (EELS) and energy-filtering TEM (EFTEM) to probe the collagen/apatite interface.

Identifying early osteoclastic resorptive lesions in feline teeth: a model for understanding the origin of multiple idiopathic root resorption.

BACKGROUND AND OBJECTIVE: Domestic cats commonly suffer from external osteoclastic tooth resorption, a disease with many similarities to human multiple idiopathic root resorption. In both diseases, it is unclear whether anatomical features of the tooth surface are associated with a predisposition for resorptive lesions. The aim of the present study was to investigate the origin and progression of early feline osteoclastic resorptive lesions in teeth exhibiting no clinical signs of disease. MATERIAL AND METHODS: The entire surfaces of 138 teeth from 13 adult cats were analysed using back-scattered electron microscopy. The distribution of lesions was assessed by tooth type, location and between individuals. RESULTS: Seventy-three (53%) teeth showed at least one resorptive lesion. Eleven (85%) cats had lesions, and there was a significant association between increasing age and incidence of resorptive lesions. The highest frequency occurred in mandibular molars (82%). On average, there were 3.5 lesions per tooth. Fifty-two (38%) teeth featured resorptive lesions at the cemento-enamel junction. Twenty-three per cent of teeth with resorptive lesions showed evidence of repair of lesions that was limited to the root surface. There was no evidence of repair of resorptive lesions at the cemento-enamel junction. CONCLUSION: Resorption is prevalent without evidence of clinical disease, and occurred at younger ages than previously reported. It can initiate anywhere on the root surface, but lack of repair of lesions at the cemento-enamel junction indicates that mechanisms of replacement are absent or compromised in this region. Whereas resorption of the root may undergo repair, resorption at the cervix may progress to clinically evident lesions.