A randomised controlled trial and cost-effectiveness evaluation of "booster" interventions to sustain increases in physical activity in middle-aged adults in deprived urban neighbourhoods

Background: Systematic reviews have identified a range of brief interventions which increase physical activity in previously sedentary people. There is an absence of evidence about whether follow up beyond three months can maintain long term physical activity. This study assesses whether it is worth providing motivational interviews, three months after giving initial advice, to those who have become more active. Methods/Design: Study candidates (n = 1500) will initially be given an interactive DVD and receive two telephone follow ups at monthly intervals checking on receipt and use of the DVD. Only those that have increased their physical activity after three months (n = 600) will be randomised into the study. These participants will receive either a "mini booster" (n = 200), "full booster" (n = 200) or no booster (n = 200). The "mini booster" consists of two telephone calls one month apart to discuss physical activity and maintenance strategies. The "full booster" consists of a face-to-face meeting with the facilitator at the same intervals. The purpose of these booster sessions is to help the individual maintain their increase in physical activity. Differences in physical activity, quality of life and costs associated with the booster interventions, will be measured three and nine months from randomisation. The research will be conducted in 20 of the most deprived neighbourhoods in Sheffield, which have large, ethnically diverse populations, high levels of economic deprivation, low levels of physical activity, poorer health and shorter life expectancy. Participants will be recruited through general practices and community groups, as well as by postal invitation, to ensure the participation of minority ethnic groups and those with lower levels of literacy. Sheffield City Council and Primary Care Trust fund a range of facilities and activities to promote physical activity and variations in access to these between neighbourhoods will make it possible to examine whether the effectiveness of the intervention is modified by access to community facilities. A one-year integrated feasibility study will confirm that recruitment targets are achievable based on a 10% sample.Discussion: The choice of study population, study interventions, brief intervention preceding the study, and outcome measure are discussed

Cough quality in children: a comparison of subjective vs. bronchoscopic findings

BACKGROUND: Cough is the most common symptom presenting to doctors. The quality of cough (productive or wet vs dry) is used clinically as well as in epidemiology and clinical research. There is however no data on the validity of cough quality descriptors. The study aims were to compare (1) cough quality (wet/dry and brassy/non-brassy) to bronchoscopic findings of secretions and tracheomalacia respectively and, (2) parent's vs clinician's evaluation of the cough quality (wet/dry). METHODS: Cough quality of children (without a known underlying respiratory disease) undergoing elective bronchoscopy was independently evaluated by clinicians and parents. A 'blinded' clinician scored the secretions seen at bronchoscopy on pre-determined criteria and graded (1 to 6). Kappa (K) statistics was used for agreement, and inter-rater and intra-rater agreement examined on digitally recorded cough. A receiver operating characteristic (ROC) curve was used to determine if cough quality related to amount of airway secretions present at bronchoscopy. RESULTS: Median age of the 106 children (62 boys, 44 girls) enrolled was 2.6 years (IQR 5.7). Parent's assessment of cough quality (wet/dry) agreed with clinicians' (K = 0.75, 95%CI 0.58–0.93). When compared to bronchoscopy (bronchoscopic secretion grade 4), clinicians' cough assessment had the highest sensitivity (0.75) and specificity (0.79) and were marginally better than parent(s). The area under the ROC curve was 0.85 (95%CI 0.77–0.92). Intra-observer (K = 1.0) and inter-clinician agreement for wet/dry cough (K = 0.88, 95%CI 0.82–0.94) was very good. Weighted K for inter-rater agreement for bronchoscopic secretion grades was 0.95 (95%CI 0.87–1). Sensitivity and specificity for brassy cough (for tracheomalacia) were 0.57 and 0.81 respectively. K for both intra and inter-observer clinician agreement for brassy cough was 0.79 (95%CI 0.73–0.86). CONCLUSIONS: Dry and wet cough in children, as determined by clinicians and parents has good clinical validity. Clinicians should however be cognisant that children with dry cough may have minimal to mild airway secretions. Brassy cough determined by respiratory physicians is highly specific for tracheomalacia

Evidence for Avian Intrathoracic Air Sacs in a New Predatory Dinosaur from Argentina

Background: Living birds possess a unique heterogeneous pulmonary system composed of a rigid, dorsally-anchored lung and several compliant air sacs that operate as bellows, driving inspired air through the lung. Evidence from the fossil record for the origin and evolution of this system is extremely limited, because lungs do not fossilize and because the bellow-like air sacs in living birds only rarely penetrate (pneumatize) skeletal bone and thus leave a record of their presence. Methodology/Principal Findings: We describe a new predatory dinosaur from Upper Cretaceous rocks in Argentina, Aerosteon riocoloradensis gen. et sp. nov., that exhibits extreme pneumatization of skeletal bone, including pneumatic hollowing of the furcula and ilium. In living birds, these two bones are pneumatized by diverticulae of air sacs (clavicular, abdominal) that are involved in pulmonary ventilation. We also describe several pneumatized gastralia (‘‘stomach ribs’’), which suggest that diverticulae of the air sac system were present in surface tissues of the thorax. Conclusions/Significance: We present a four-phase model for the evolution of avian air sacs and costosternal-driven lung ventilation based on the known fossil record of theropod dinosaurs and osteological correlates in extant birds: (1) Phase I—Elaboration of paraxial cervical air sacs in basal theropods no later than the earliest Late Triassic. (2) Phase II—Differentiation of avian ventilatory air sacs, including both cranial (clavicular air sac) and caudal (abdominal air sac) divisions, in basal tetanurans during the Jurassic. A heterogeneous respiratory tract wit

Identifying Molecular Effects of Diet through Systems Biology: Influence of Herring Diet on Sterol Metabolism and Protein Turnover in Mice

BACKGROUND: Changes in lifestyle have resulted in an epidemic development of obesity-related diseases that challenge the healthcare systems worldwide. To develop strategies to tackle this problem the focus is on diet to prevent the development of obesity-associated diseases such as cardiovascular disease (CVD). This will require methods for linking nutrient intake with specific metabolic processes in different tissues. METHODOLOGY/PRINCIPAL FINDING: Low-density lipoprotein receptor-deficient (Ldlr -/-) mice were fed a high fat/high sugar diet to mimic a westernized diet, being a major reason for development of obesity and atherosclerosis. The diets were supplemented with either beef or herring, and matched in macronutrient contents. Body composition, plasma lipids and aortic lesion areas were measured. Transcriptomes of metabolically important tissues, e.g. liver, muscle and adipose tissue were analyzed by an integrated approach with metabolic networks to directly map the metabolic effects of diet in these different tissues. Our analysis revealed a reduction in sterol metabolism and protein turnover at the transcriptional level in herring-fed mice. CONCLUSION: This study shows that an integrated analysis of transcriptome data using metabolic networks resulted in the identification of signature pathways. This could not have been achieved using standard clustering methods. In particular, this systems biology analysis could enrich the information content of biomedical or nutritional data where subtle changes in several tissues together affects body metabolism or disease progression. This could be applied to improve diets for subjects exposed to health risks associated with obesity

The first oviraptorosaur (Dinosauria: Theropoda) bonebed: Evidence of gregarious behaviour in a maniraptoran theropod

A monodominant bonebed of Avimimus from the Nemegt Formation of Mongolia is the first oviraptorosaur bonebed described and the only recorded maniraptoran bonebed from the Late Cretaceous. Cranial elements recovered from the bonebed provide insights on the anatomy of the facial region, which was formerly unknown in Avimimus. Both adult and subadult material was recovered from the bonebed, but small juveniles are underrepresented. The taphonomic and sedimentological evidence suggests that the Avimimus bonebed represents a perimortem gregarious assemblage. The near absence of juveniles in the bonebed may be evidence of a transient age-segregated herd or ‘flock’, but the behaviour responsible for this assemblage is unclear. Regardless, the Avimimus bonebed is the first evidence of gregarious behaviour in oviraptorosaurs, and highlights a potential trend of increasing gregariousness in dinosaurs towards the end of the Mesozoic

Metadherin Contributes to the Pathogenesis of Diffuse Large B-cell Lymphoma

BACKGROUND: Metadherin (MTDH) has been demonstrated as a potentially crucial mediator of various types of human malignancies. However, the expression and role of MTDH in diffuse large-B-cell lymphoma (DLBCL) have not been reported yet. This study aimed to illuminate the role of MTDH in the pathogenesis of DLBCL. METHODOLOGY/PRINCIPAL FINDINGS: A remarkable elevation of MTDH on mRNA level was detected in DLBCL tissues by quantitative polymerase chain reaction (PCR). Using Western-blot analysis we found that the expression of MTDH protein was significantly upregulated in DLBCL cell lines and DLBCL tissues compared with peripheral blood mononuclear cells (PBMCs) from healthy samples and tissues from patients of reactive hyperplasia of lymph node. The results showed high expression of MTDH in 23 of 30 (76.67%) DLBCL tissues by using immunohistochemical analysis and the over expression of MTDH was strongly correlated to the clinical staging of patients with DLBCL (P<0.05). Furthermore, the finding suggested that the increase of MTDH in DLBCL cells could distinctly enhance cell proliferation and inhibit cell apoptosis; meanwhile, inhibition of MTDH expression by specific siRNA clearly enhanced LY8 cell apoptosis. Upregulation of MTDH elevated the protein level of total β-catenin and translocation of β-catenin to the nucleus directly or indirectly. Knockdown of MTDH decreased the level of total, cytoplasmic β-catenin and reduced nuclear accumulation of β-catenin protein. This indicated that the function of MTDH on the development of DLBCL was mediated through regulation of Wnt/β-catenin signaling pathway. CONCLUSIONS/SIGNIFICANCE: Our results suggest that MTDH contributes to the pathogenesis of DLBCL mediated by activation of Wnt/β-catenin pathway. This novel study may contribute to further investigation on the useful biomarkers and potential therapeutic target in the DLBCL patients

A Nomenclature for Vertebral Fossae in Sauropods and Other Saurischian Dinosaurs

The axial skeleton of extinct saurischian dinosaurs (i.e., theropods, sauropodomorphs), like living birds, was pneumatized by epithelial outpocketings of the respiratory system. Pneumatic signatures in the vertebral column of fossil saurischians include complex branching chambers within the bone (internal pneumaticity) and large chambers visible externally that are bounded by neural arch laminae (external pneumaticity). Although general aspects of internal pneumaticity are synapomorphic for saurischian subgroups, the individual internal pneumatic spaces cannot be homologized across species or even along the vertebral column, due to their variability and absence of topographical landmarks. External pneumatic structures, in contrast, are defined by ready topological landmarks (vertebral laminae), but no consistent nomenclatural system exists. This deficiency has fostered confusion and limited their use as character data in phylogenetic analysis.We present a simple system for naming external neural arch fossae that parallels the one developed for the vertebral laminae that bound them. The nomenclatural system identifies fossae by pointing to reference landmarks (e.g., neural spine, centrum, costal articulations, zygapophyses). We standardize the naming process by creating tripartite names from “primary landmarks,” which form the zygodiapophyseal table, “secondary landmarks,” which orient with respect to that table, and “tertiary landmarks,” which further delineate a given fossa.The proposed nomenclatural system for lamina-bounded fossae adds clarity to descriptions of complex vertebrae and allows these structures to be sourced as character data for phylogenetic analyses. These anatomical terms denote potentially homologous pneumatic structures within Saurischia, but they could be applied to any vertebrate with vertebral laminae that enclose spaces, regardless of their developmental origin or phylogenetic distribution

New Specimens of Nemegtomaia from the Baruungoyot and Nemegt Formations (Late Cretaceous) of Mongolia

Two new specimens of the oviraptorid theropod Nemegtomaia barsboldi from the Nemegt Basin of southern Mongolia are described. Specimen MPC-D 107/15 was collected from the upper beds of the Baruungoyot Formation (Campanian-Maastrichtian), and is a nest of eggs with the skeleton of the assumed parent of Nemegtomaia on top in brooding position. Much of the skeleton was damaged by colonies of dermestid coleopterans prior to its complete burial. However, diagnostic characters are recovered from the parts preserved, including the skull, partial forelimbs (including the left hand), legs, and distal portions of both feet. Nemegtomaia represents the fourth known genus of oviraptorid for which individuals have been found on nests of eggs. The second new specimen, MPC-D 107/16, was collected a few kilometers to the east in basal deposits of the Nemegt Formation, and includes both hands and femora of a smaller Nemegtomaia individual. The two formations and their diverse fossil assemblages have been considered to represent sequential time periods and different environments, but data presented here indicate partial overlap across the Baruungoyot-Nemegt transition. All other known oviraptorids from Mongolia and China are known exclusively from xeric or semi-arid environments. However, this study documents that Nemegtomaia is found in both arid/aeolian (Baruungoyot Formation) and more humid/fluvial (Nemegt Formation) facies

Theropod Fauna from Southern Australia Indicates High Polar Diversity and Climate-Driven Dinosaur Provinciality

The Early Cretaceous fauna of Victoria, Australia, provides unique data on the composition of high latitude southern hemisphere dinosaurs. We describe and review theropod dinosaur postcranial remains from the Aptian–Albian Otway and Strzelecki groups, based on at least 37 isolated bones, and more than 90 teeth from the Flat Rocks locality. Several specimens of medium- and large-bodied individuals (estimated up to ∼8.5 metres long) represent allosauroids. Tyrannosauroids are represented by elements indicating medium body sizes (∼3 metres long), likely including the holotype femur of Timimus hermani, and a single cervical vertebra represents a juvenile spinosaurid. Single specimens representing medium- and small-bodied theropods may be referrable to Ceratosauria, Ornithomimosauria, a basal coelurosaur, and at least three taxa within Maniraptora. Thus, nine theropod taxa may have been present. Alternatively, four distinct dorsal vertebrae indicate a minimum of four taxa. However, because most taxa are known from single bones, it is likely that small-bodied theropod diversity remains underestimated. The high abundance of allosauroids and basal coelurosaurs (including tyrannosauroids and possibly ornithomimosaurs), and the relative rarity of ceratosaurs, is strikingly dissimilar to penecontemporaneous dinosaur faunas of Africa and South America, which represent an arid, lower-latitude biome. Similarities between dinosaur faunas of Victoria and the northern continents concern the proportional representatation of higher clades, and may result from the prevailing temperate–polar climate of Australia, especially at high latitudes in Victoria, which is similar to the predominant warm–temperate climate of Laurasia, but distinct from the arid climate zone that covered extensive areas of Gondwana. Most dinosaur groups probably attained a near-cosmopolitan distribution in the Jurassic, prior to fragmentation of the Pangaean supercontinent, and some aspects of the hallmark ‘Gondwanan’ fauna of South America and Africa may therefore reflect climate-driven provinciality, not vicariant evolution driven by continental fragmentation. However, vicariance may still be detected at lower phylogenetic levels

Vertebral Pneumaticity in the Ornithomimosaur Archaeornithomimus (Dinosauria: Theropoda) Revealed by Computed Tomography Imaging and Reappraisal of Axial Pneumaticity in Ornithomimosauria

Among extant vertebrates, pneumatization of postcranial bones is unique to birds, with few known exceptions in other groups. Through reduction in bone mass, this feature is thought to benefit flight capacity in modern birds, but its prevalence in non-avian dinosaurs of variable sizes has generated competing hypotheses on the initial adaptive significance of postcranial pneumaticity. To better understand the evolutionary history of postcranial pneumaticity, studies have surveyed its distribution among non-avian dinosaurs. Nevertheless, the degree of pneumaticity in the basal coelurosaurian group Ornithomimosauria remains poorly known, despite their potential to greatly enhance our understanding of the early evolution of pneumatic bones along the lineage leading to birds. Historically, the identification of postcranial pneumaticity in non-avian dinosaurs has been based on examination of external morphology, and few studies thus far have focused on the internal architecture of pneumatic structures inside the bones. Here, we describe the vertebral pneumaticity of the ornithomimosaur Archaeornithomimus with the aid of X-ray computed tomography (CT) imaging. Complementary examination of external and internal osteology reveals (1) highly pneumatized cervical vertebrae with an elaborate configuration of interconnected chambers within the neural arch and the centrum; (2) anterior dorsal vertebrae with pneumatic chambers inside the neural arch; (3) apneumatic sacral vertebrae; and (4) a subset of proximal caudal vertebrae with limited pneumatic invasion into the neural arch. Comparisons with other theropod dinosaurs suggest that ornithomimosaurs primitively exhibited a plesiomorphic theropod condition for axial pneumaticity that was extended among later taxa, such as Archaeornithomimus and large bodied Deinocheirus. This finding corroborates the notion that evolutionary increases in vertebral pneumaticity occurred in parallel among independent lineages of bird-line archosaurs. Beyond providing a comprehensive view of vertebral pneumaticity in a non-avian coelurosaur, this study demonstrates the utility and need of CT imaging for further clarifying the early evolutionary history of postcranial pneumaticity