Point-of-care ultrasound for diagnosing extrapulmonary TB.

Despite the high morbidity and mortality globally, standard microbiologic diagnosis for TB requires laboratory infrastructure inaccessible in many resource-limited areas and may be insufficient for identifying extrapulmonary disease. Point-of-care (POC) ultrasound facilitates visualization of extrapulmonary manifestations, permitting laboratory-independent diagnosis, but its diagnostic utility remains unclear.We conducted a systematic review of five online databases for studies reporting ultrasound findings among cases with and without extrapulmonary TB (EPTB). A minimum of two authors independently screened and reviewed each article, and extracted data elements of interest. We conducted a series of univariate meta-analyses using a random-effects model to calculate the pooled effect estimate and 95% confidence interval (CI) for each outcome: sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).Of 279 articles identified, 6 were included. There were 699 cases of EPTB among 1,633 participants. The pooled sensitivity estimate was 0.72 (95% CI 0.57-0.88). The pooled specificity estimate was 0.77 (95% CI 0.63-0.90). The pooled PPV and NPV estimates were respectively 0.67 (95% CI 0.47-0.87) and 0.85 (95% CI 0.77-0.93).POC ultrasound showed modest test characteristics for diagnosing EPTB, which may constitute an improvement over some currently available diagnostics..

Validation of the NIH Toolbox in Individuals with Neurologic Disorders.

OBJECTIVE: Individuals with spinal cord injury (SCI), traumatic brain injury (TBI), and stroke experience a variety of neurologically related deficits across multiple domains of function. The NIH Toolbox for the Assessment of Neurological and Behavioral Function (NIHTB) examines motor, sensation, cognition, and emotional functioning. The purpose of this paper is to establish the validity of the NIHTB in individuals with neurologic conditions. METHODS: Community-dwelling individuals with SCI (n = 209), TBI (n = 184), or stroke (n = 211) completed the NIHTB. Relative risks for impaired performance were examined relative to a matched control groups. RESULTS: The largest group differences were observed on the Motor domain and for the Fluid Cognition measures. All groups were at increased risk for motor impairment relative to normative standards and matched controls. Fluid cognitive abilities varied across groups such that individuals with stroke and TBI performed more poorly than individuals with SCI; increased relative risks for impaired fluid cognition were seen for individuals in the stroke and TBI groups, but not for those in the SCI group. All three neurologic groups performed normally on most measures in the Sensation Battery, although TBI participants evidenced increased risk for impaired odor identification and the stroke group showed more vision difficulties. On the Emotion Battery, participants in all three groups showed comparably poor psychological well-being, social satisfaction, and self-efficacy, whereas the TBI group also evidenced slightly increased negative affect. CONCLUSIONS: Data provide support for the validity of the NIHTB in individuals with neurologic conditions.

Nasal cytokine responses to natural colds in asthmatic children.

BACKGROUND: The mechanisms by which viruses induce asthma exacerbations are not well understood. OBJECTIVE: We characterized fluctuations in nasal aspirate cytokines during naturally occurring respiratory viral infections in children with asthma. METHODS: Sixteen children underwent home collections of nasal aspirates when they were without cold symptoms and again during self-reported respiratory illnesses. The presence of viral infection was ascertained by multiplex PCR. Cytokines were measured using multiplex immune assay. mRNA expression for selected markers of viral infection was measured using RT-PCR. A cumulative respiratory symptom score was calculated for each day of measurement. Generalized estimated equations were used to evaluate associations between viral infection and marker elevation, and between marker elevation and symptom score. RESULTS: The 16 patients completed a total of 37 weeks of assessment (15 'well' weeks; 22 self-assessed 'sick' weeks). Viral infections were detected in 3 of the 'well' weeks and 17 of the 'sick' weeks (10 rhinovirus, three coronavirus, two influenza A, two influenza B, two respiratory syncytial virus, one parainfluenza). Compared to virus-negative well weeks, nasal aspirate IFN-γ, CXCL8/IL-8, CXCL10/IP-10, CCL5/RANTES, CCL11/eotaxin-1, CCL2/MCP-1, CCL4/MIP-1ß, CCL7/MCP-3, and CCL20/MIP3α protein levels increased during virus-positive sick weeks. Only a subset of cytokines (IFN-γ, CXCL8, CCL2, CCL4, CCL5, and CCL20) correlated with self-reported respiratory tract symptoms. While many aspirates were dilute and showed no mRNA signal, viral infection significantly increased the number of samples that were positive for IFN-λ1, IFN-λ2/3, TLR3, RIG-I, and IRF7 mRNA. CONCLUSIONS AND CLINICAL RELEVANCE: We conclude that in children with asthma, naturally occurring viral infections apparently induce a robust innate immune response including expression of specific chemokines, IFNs, and IFN-responsive genes.

Bayesian Functional Data Analysis Using WinBUGS.

We provide user friendly software for Bayesian analysis of functional data models using WinBUGS 1.4. The excellent properties of Bayesian analysis in this context are due to: (1) dimensionality reduction, which leads to low dimensional projection bases; (2) mixed model representation of functional models, which provides a modular approach to model extension; and (3) orthogonality of the principal component bases, which contributes to excellent chain convergence and mixing properties. Our paper provides one more, essential, reason for using Bayesian analysis for functional models: the existence of software.

Does testosterone mediate the trade-off between nestling begging and growth in the canary (Serinus canaria)?

Nestling birds solicit food from their parents with vigorous begging displays, involving posturing, jostling and calling. In some species, such as canaries, begging is especially costly because it causes a trade off against nestling growth. Fitness costs of begging like this are predicted by evolutionary theory because they function to resolve conflicts of interest within the family over the provision of parental investment. However, the mechanism that links these costs with nestling behaviour remains unclear. In the present study, we determine if the relationships between nestling androgen levels, nestling begging intensities and nestling growth rates are consistent with the hypothesis that testosterone is responsible for the trade-off between begging and growth. We test this idea with a correlational study, using fecal androgens as a non-invasive method for assaying nestling androgen levels. Our results show that fecal androgen levels are positively correlated with nestling begging intensity, and reveal marked family differences in each trait. Furthermore, changes in fecal androgen levels between 5 and 8 days after hatching are positively associated with changes in nestling begging intensity, and negatively associated with nestling growth during this time. Although these correlational results support our predictions, we suggest that that experimental manipulations are now required to test the direct or indirect role of testosterone in mediating the trade-off between begging and growth.

In-situ engineering of cartilage repair: a pre-clinical in-vivo exploration of a novel system.

This investigation explores a new cartilage repair technique that uses a novel method to secure a non-woven multifilamentous scaffold in the defect site after microfracture. The hypothesis is that a scaffold provides a larger surface area for attachment and proliferation of the mesenchymal stem cells that migrate from the bone marrow. Two in-vivo studies were undertaken in an ovine model. The first study, which lasted for 8 weeks, aimed to compare the new technique with microfracture. Chondral defects, 7 mm in diameter, were created in both femoral medial condyles of five ewes. One defect was treated with the new technique while the contralateral knee was treated with microfracture alone. The results revealed that the quantity of repair tissue was significantly greater in the defects treated with the new system. The second study had two time points, 3 and 6 months, and used 13 ewes. In this study, both defects were treated with the new technique but one received additional subchondral drilling in order to stimulate extra tissue growth. The majority of the implants had good tissue induction, filling 50-100 per cent of the defect volume, while the compressive modulus of the repairs was in the range of 40-70 per cent of that for the surrounding cartilage. In addition, hyaline-like cartilage was seen in all the repairs which had the additional drilling of the subchondral bone.

Developmental stress, social rank and song complexity in the European starling (Sturnus vulgaris).

Bird song is a sexually selected trait and females have been shown to prefer males that sing more complex songs. However, for repertoire size to be an honest signal of male quality it must be associated with some form of cost. This experiment investigates the effects of food restriction and social status during development on song complexity in the European starling (Sturnus vulgaris). Birds that experienced an unpredictable food supply early in life produced a significantly smaller repertoire of song phrases than those with a constant food supply. Social status during development was also significantly correlated with repertoire size, with dominant birds producing more phrase types. This study therefore provides novel evidence that social as well as nutritional history may be important in shaping the song signal in this species.

Song as an honest signal of developmental stress in the zebra finch (Taeniopygia guttata).

In a wide range of bird species, females have been shown to express active preferences for males that sing more complex songs. Current sexual selection theory predicts that for this signal to remain an honest indicator of male quality, it must be associated with an underlying cost of development or maintenance. There has been considerable debate questioning the costs associated with song production and learning. Recently, the nutritional stress hypothesis proposed that song complexity could act as an indicator of early developmental history, since the song control nuclei in the brain are laid down early in life. Here we test the nutritional stress hypothesis, by investigating the effects of dietary stress on the quality of adult song produced. In addition, we tested the effects of elevated corticosterone during development on song production to test its possible involvement in mediating the effects of developmental stress. The results demonstrate that both dietary restriction and elevated corticosterone levels significantly reduced nestling growth rates. In addition, we found that experimentally stressed birds developed songs with significantly shorter song motif duration and reduced complexity. These results provide novel experimental evidence that complex song repertoires may have evolved as honest signals of male quality, by indicating early developmental rearing conditions.

Song as an honest signal of past developmental stress in the European starling (Sturnus vulgaris).

Bird song is a sexually selected male trait where females select males on the basis of song quality. It has recently been suggested that the quality of the adult male song may be determined by nutritional stress during early development. Here, we test the 'nutritional-stress hypothesis' using the complex song of the European starling. Fledgling starlings were kept under experimental treatment (unpredictable short-term food deprivations) or control conditions (ad libitum food supply), for three months immediately after independence. We measured their physiological and immune responses during the treatment and recorded song production during the following spring. Birds in the experimental group showed increased mass during the treatment and also a significantly suppressed humoral response compared with birds in the control group. There was no difference between the groups in the cell-mediated response. Next spring, males in the experimental group spent less time singing, sang fewer song bouts, took longer to start singing and also sang significantly shorter song bouts. These data support the hypothesis that both the quality and quantity of song produced by individual birds reflect past developmental stress. The results also suggest the 'nutritional-stress hypothesis' is best considered as a more general 'developmental-stress hypothesis'.

Demographic and occupational effects on the activity levels of normal subjects in the United Kingdom.

A study of activity levels, measured in steps per day, was made of 293 subjects from several parts of the United Kingdom. Each subject wore a pedometer adjacent to the hip for two weeks. The average number of steps taken each day over a two-week period was recorded together with additional details such as age and occupation. A general decline in activity with age was observed, which varied slightly for men and women. At twenty years of age the sample of men typically walked about 9,000 steps per day and women 9,200 steps per day, declining to 6,100 and 5,750 steps per day for men and women respectively at sixty years of age. Activity was observed to vary considerably from day to day and was more pronounced for men. The mean number of steps per day for a wide range of occupational groups varied from around 4,500 steps per day for retired persons to 12,700 steps per day for postmen. The activity data was re-analysed to remove the influence of age and gender. The activity of most occupational groups then fell within a relatively narrow range of approximately 7,700 to 8,850 steps per day. The exceptions to this were postmen, nurses and technicians, with averages of 12,750, 9,950 and 9,900 steps per day respectively, and software programmers averaging only 5,250 steps per day. Activity levels for groups of subjects from different parts of the United Kingdom were compared, including Leeds and Bradford, Belfast, Teesside, County Durham and Edinburgh. When the number of subjects in each group was sufficiently large with a wide spread of ages and occupational types, it was found that demography had little effect upon the level of activity. This study provides a substantial new database, based on the UK population. In addition, the assumption that one million cycles in vitro is equivalent to one year in vivo is well supported and relevant to simulator studies. (Hip International 2002; 1: 28-36).

The influence of flicker rate on plasma corticosterone levels of European starlings, Sturnus vulgaris.

Recent reviews have highlighted the differences between human and avian vision with regard to temporal resolution and the potential problems it may cause for avian welfare and video playback experiments. Birds tend to have much higher critical fusion frequencies than do humans (>100 Hz vs 50-60 Hz in humans), which means that they perceive light as flickering up to and over 100 Hz. This is higher than most television monitors (which have refresh rates of 50 or 60 Hz) and normal fluorescent lighting (100 or 120 Hz), and because humans find flickering light aversive, it has been suggested that birds will as well. If this were the case, then there would be welfare implications of maintaining them under such lighting and also a potential effect on their behavioral responses in video playback experiments. However, there is some behavioral evidence that indicates that birds do not appear to find flicker aversive and may even prefer flickering lighting. The authors aimed to determine whether a passerine, the European starling, found flicker aversive by measuring the corticosterone stress response in birds maintained under high- or low-frequency fluorescent lighting (35-40 kHz vs 100 Hz) for 1 or 24 h. The results suggest that low-frequency lighting is potentially more stressful because, where differences exist, birds in the low-frequency treatment always showed higher basal corticosterone. However, the evidence is not consistent because in half of the blocks, there were no significant treatment effects and, where there were, the time course of the effects was variable.

Translocation portals for the substrates and products of a viral transcription complex: the bluetongue virus core.

The bluetongue virus core is a molecular machine that simultaneously and repeatedly transcribes mRNA from 10 segments of viral double-stranded RNA, packaged in a liquid crystalline array. To determine how the logistical problems of transcription within a sealed shell are solved, core crystals were soaked with various ligands and analysed by X-ray crystallography. Mg(2+) ions produce a slight expansion of the capsid around the 5-fold axes. Oligonucleotide soaks demonstrate that the 5-fold pore, opened up by this expansion, is the exit site for mRNA, whilst nucleotide soaks pinpoint a separate binding site that appears to be a selective channel for the entry and exit of substrates and by-products. Finally, nucleotides also bind to the outer core layer, providing a substrate sink.

The effect of activity levels of total hip arthroplasty patients on socket penetration.

Survivorship of total hip arthroplasties (THAs) has been linked to penetration of the femoral head into the polyethylene acetabular cup and to polyethylene wear. The activity level of patients with THAs is considered to be an important factor affecting wear, and the purpose of this study was to explore the relationship between activity as recorded by pedometers and cup penetration. The measurement of daily activity levels of normal subjects and THA patients of various ages are discussed in another article ([1]). Subjects were monitored continuously during 2- to 4-week periods using simple pedometer devices. Patients (n = 54; mean age, 58 years) from the Centre for Hip Surgery at Wrightington Hospital for whom the penetration data also were available were included in the study. The average activity level for the patient group was 1.426 million loading cycles on each hip joint per year. Radiographic penetration measurements were compared for 81 hips in 54 patients with a mean follow-up of 13.1 years (range, 1.3-26.4 years). The overall correlation of penetration with implantation period is known to be poor, however, and did not improve significantly when the penetration was plotted against a new parameter that took account of not only implant life, but also the level of activity and patient weight. The considerable scatter of penetration levels was noted to increase with increasing implantation period, which indicates that in the multifactorial problem of polyethylene wear, other factors, particularly femoral head surface finish or polyethylene deterioration, may predominate.

Comparative study of the activity of total hip arthroplasty patients and normal subjects.

The walking activity of normal subjects and total hip arthroplasty (THA) patients from the Wrightington Hospital for Joint Disease and The General Infirmary at Leeds was assessed by means of electronic pedometers. The principal objectives were to establish the extent to which joint arthroplasty patients recover their activity relative to normal subjects and to establish the number of loading cycles to which prostheses should be subjected in joint simulator studies of implant performance. A further objective was to establish an experimental procedure for the assessment of the role of activity in contributing to the well-known scatter in the measurements of femoral head penetration into acetabular cups in in vivo studies of implant performance. The last-mentioned issue is addressed in another article ([1]). The walking activity of 2 normal subjects of disparate ages was assessed during 1 full year. It was concluded that fair estimates of activity could be achieved by recording pedometer readings during successive 2- to 4-week periods. This approach was adopted in the full assessment of the walking activity of cohorts of normal subjects and THA patients. Linear regression expressions relating the number of steps taken daily and the annual number of loading cycles on each leg to age are presented for normal subjects and THA patients. In all cases, activity declines with age, but it is shown that total joint arthroplasty is not at all restrictive on walking activity-a remarkable testimony to the efficacy of total joint arthroplasty. Attention is drawn, however, to different levels of activity of THA patients recorded in the present United Kingdom study and a similar survey conducted in California.

Testosterone influences basal metabolic rate in male house sparrows: a new cost of dominance signalling?

Sexually selected signals of individual dominance have profound effects on access to resources, mate choice and gene flow. However, why such signals should honestly reflect individual quality is poorly understood. Many such signals are known to develop under the influence of testosterone. We conducted an experiment in male house sparrows in which testosterone was manipulated independently during two periods: before the onset of the breeding season and prior to the autumn moult. We then measured the effects of these manipulations on basal metabolic rate and on the size of the chest bib, a sexually selected signal. The results demonstrate that testosterone simultaneously affects both signal development and basal metabolic rate in the house sparrow (Passer domesticus). This evidence, therefore, supports a novel conclusion: that testosterone-dependent signals act as honest indicators of male quality possibly because only high-quality individuals can sustain the energetic costs associated with signal development.

The effect of femoral head diameter upon lubrication and wear of metal-on-metal total hip replacements.

It has been found that a remarkable reduction in the wear of metal-on-metal hip joints can be achieved by simply increasing the diameter of the joint. A tribological evaluation of metal-on-metal joints of 16, 22.225, 28 and 36 mm diameter was conducted in 25 per cent bovine serum using a hip joint simulator. The joints were subject to dynamic motion and loading cycles simulating walking for both lubrication and wear studies. For each size of joint in the lubrication study, an electrical resistivity technique was used to detect the extent of surface separation through a complete walking cycle. Wear of each size of joint was measured gravimetrically in wear tests of at least 2 x 10(6) cycles duration. Joints of 16 and 22.225 mm diameter showed no surface separation in the lubrication study. This suggested that wear would be proportional to the sliding distance and hence joint size in this boundary lubrication regime. A 28 mm diameter joint showed only limited evidence of surface separation suggesting that these joints were operating in a mixed lubrication regime. A 36 mm diameter joint showed surface separation for considerable parts of each walking cycle and hence evidence of the formation of a protective lubricating film. Wear testing of 16 and 22.225 mm diameter metal-on-metal joints gave mean wear rates of 4.85 and 6.30 mm3/10(6) cycles respectively. The ratio of these wear rates, 0.77, is approximately the same as the joint diameters ratio, 16/22.225 or 0.72, as expected from simple wear theory for dry or boundary lubrication conditions. No bedding-in was observed with these smaller diameter joints. For the 28 mm diameter joint, from 0 to 2 x 10(6) cycles, the mean wear rate was 1.62 mm3/10(6) cycles as the joints bedded-in. Following bedding-in, from 2.0 x 10(6) to 4.7 x 10(6) cycles, the wear rate was 0.54 mm3/10(6) cycles. As reported previously by Goldsmith et al. in 2000 [1], the mean steady state wear rate of the 36 mm diameter joints was lower than those of all the other diameters at 0.07 mm3/10(6) cycles. For a range of joints of various diameters, subjected to identical test conditions, mean wear rates differed by almost two orders of magnitude. This study has demonstrated that the application of sound tribological principles to prosthetic design can reduce the wear of metal-on-metal joints, using currently available materials, to a negligible level.

Wear of fixed bearing and rotating platform mobile bearing knees subjected to high levels of internal and external tibial rotation.

In order to extend the lifetime of total knee replacements (TKR) in vivo, reduction of the volumetric wear rate of ultra high molecular weight polyethylene (UHMWPE) bearings remains an important goal. The volume of wear debris generated in fixed bearing total knee devices increases significantly when subjected to higher levels of internal-external rotation and anterior-posterior displacement. Six PFC Sigma fixed bearing TKR were compared with six LCS rotating platform mobile bearing knees using a physiological knee simulator with high rotation kinematic inputs. The rotating platform polyethylene inserts exhibited a mean wear rate which was one-third of that of the fixed bearing inserts despite having increased femoral contact areas and additional tibial wear surfaces. The rotating platform design decouples knee motions, by allowing unidirectional motion at the tray-insert articulation, which reduces rotation at the femoral-insert counterface. This translation of complex knee motions into more unidirectional motions results in molecular orientation of the UHMWPE and reduced volumetric wear.

A frictional study of total hip joint replacements.

Polymeric wear debris produced by articulation of the femoral head against the ultra-high-molecular-weight polyethylene socket of a total hip replacement has been implicated as the main cause of osteolysis and subsequent failure of these implants. Potential solutions to this problem are to employ hard bearing surface combinations such as metal-on-metal or ceramic-on-ceramic prostheses. The aim of this study was to investigate the difference in lubrication modes and friction of a range of material combinations using synthetic and biological fluids as the lubricants. The experimental results were compared with theoretical predictions of film thicknesses and lubrication modes. A strong correlation was observed between experiment and theory when employing carboxy methyl cellulose (CMC) fluids as the lubricant. Under these conditions the ceramic-on-ceramic joints showed full fluid film lubrication while the metal-on-metal, metal-on-plastic, diamond-like carbon-coated stainless steel (DLC)-on-plastic and ceramic-on-plastic prostheses operated under a mixed lubrication regime. With bovine serum as the lubricant in the all ceramic joints, however, the full fluid film lubrication was inhibited due to adsorbed proteins. In the metal-on-metal joints this adsorbed protein layer acted to reduce the friction while in the ceramic coupling the friction was increased. The use of bovine serum as the lubricant also significantly increased the friction in both the metal-on-plastic and ceramic-on-plastic joints. The friction produced by the DLC-on-plastic joints depended on the quality of the coating. Those joints with a less consistent coating and therefore a higher surface roughness gave significantly higher friction than the smoother, more consistently coated heads.

Sequence and analysis of chromosome 1 of the plant Arabidopsis thaliana.

The genome of the flowering plant Arabidopsis thaliana has five chromosomes. Here we report the sequence of the largest, chromosome 1, in two contigs of around 14.2 and 14.6 megabases. The contigs extend from the telomeres to the centromeric borders, regions rich in transposons, retrotransposons and repetitive elements such as the 180-base-pair repeat. The chromosome represents 25% of the genome and contains about 6,850 open reading frames, 236 transfer RNAs (tRNAs) and 12 small nuclear RNAs. There are two clusters of tRNA genes at different places on the chromosome. One consists of 27 tRNA(Pro) genes and the other contains 27 tandem repeats of tRNA(Tyr)-tRNA(Tyr)-tRNA(Ser) genes. Chromosome 1 contains about 300 gene families with clustered duplications. There are also many repeat elements, representing 8% of the sequence.

Lack of gonadotrophin-releasing hormone (GnRH) neuron response to decreasing photoperiod in thyroidectomized male starlings (Sturnus vulgaris).

Exposure of starlings to long days initially causes reproductive maturation, but eventually leads to photorefractoriness. During photorefractoriness, gonadotrophin-releasing hormone (GnRH) decreases in the GnRH cell bodies and fibers emanating from these to the median eminence, circulating gonadotrophin concentrations decrease to a minimum, and the gonads regress. Thyroidectomy profoundly affects these photoperiodic responses. In chronically thyroidectomized starlings, gonadal responses to changes in day length are attenuated. This investigation was conducted to determine whether, in the absence of gonadal responsiveness, the GnRH system of chronically thyroidectomized starlings responds to changes in day length. Two groups of thyroidectomized male starlings were transferred from short days (8L:16D) to long days (18L:6D) for four weeks, and testicular volume increased. One group was kept on long days (TxLD) and the other was returned to short days (TxSD). Testicular volume did not decrease in the TxSD group. The GnRH neurons of the two thyroidectomized groups were compared to those of two groups of intact starlings, one of them on long days and photorefractory (ILD), the other on short days and photosensitive (ISD). Group ILD had lower numbers of GnRH-stained cells than groups TxLD, TxSD and ISD, which did not differ in this respect. Similar differences were observed for GnRH cell size in the pre-optic area (POA) and for density of staining of GnRH fibers in the median eminence. The results confirm that thyroidectomy attenuates gonadal responses to change in day length and suggest that this results from an effect upon the central nervous system rather than a peripheral effect.