The first megatheropod tracks from the Lower Jurassic upper Elliot Formation, Karoo Basin, Lesotho.

A palaeosurface with one megatheropod trackway and several theropod tracks and trackways from the Lower Jurassic upper Elliot Formation (Stormberg Group, Karoo Supergroup) in western Lesotho is described. The majority of the theropod tracks are referable to either Eubrontes or Kayentapus based on their morphological characteristics. The larger megatheropod tracks are 57 cm long and have no Southern Hemisphere equivalent. Morphologically, they are more similar to the Early Jurassic Kayentapus, as well as the much younger Upper Cretaceous ichnogenus Irenesauripus, than to other contemporaneous ichnogenera in southern Africa. Herein they have been placed within the ichnogenus Kayentapus and described as a new ichnospecies (Kayentapus ambrokholohali). The tracks are preserved on ripple marked, very fine-grained sandstone of the Lower Jurassic upper Elliot Formation, and thus were made after the end-Triassic mass extinction event (ETE). This new megatheropod trackway site marks the first occurrence of very large carnivorous dinosaurs (estimated body length >8-9 meters) in the Early Jurassic of southern Gondwana, an evolutionary strategy that was repeatedly pursued and amplified in the following ~135 million years, until the next major biotic crisis at the end-Cretaceous.

The longitudinal effect of a multi-strain probiotic on the intestinal bacterial microbiota of neonatal foals.

REASONS FOR PERFORMING THE STUDY: The microbiota plays a key role in health and disease. Probiotics are a potential way to therapeutically modify the intestinal microbiota and prevent disease. OBJECTIVES: The aim of this study was to investigate the effects of probiotics on the bacterial microbiota of foals during and after administration. STUDY DESIGN: Randomised placebo controlled field trial. METHODS: Thirty-eight healthy neonatal foals enrolled in a previous study were selected. The foals had received a multi-strain probiotic (four Lactobacillus spp. 3-4 × 103 colony-forming units (cfu)/g each, Bifidobacterium animalis spp. lactis, 1 × 103-4 cfu/g) or placebo once daily for 3 weeks. A total of 3 faecal samples were collected from each foal at 2-week intervals and assessed via metagenomic sequencing. The Wilcoxon test was used to compare data between treatment groups. RESULTS: There were no changes on the phylum, order or class level between treatment groups at any age (all P>0.05) but some significant changes in relative abundance of families. Probiotic administration did not result in an increased relative abundance of lactobacilli or bifidobacteria at any age (Lactobacillus: P = 0.9, P = 0.1 and P = 0.2, Bifidobacterium: P = 0.3, P = 0.6 and P = 0.1 for Weeks 2, 4 and 6, respectively). Lactobacillus was enriched in the probiotic group at Week 6 on LEfSe analysis (linear discriminant analysis score 0.34, P = 0 .02). There was no effect on alpha diversity (all P>0.2) or community structure when parsimony and unifrac analysis were applied (all P>0.6). CONCLUSIONS: There were limited effects of probiotic treatment on the bacterial microbiota of foals. The studied probiotic based on lactobacilli and bifidobacteria has a limited potential for therapeutic modification of the gastrointestinal microbiota.

False-negative HIV-1 polymerase chain reaction in a 15-month-old boy with HIV-1 subtype C infection.

Polymerase chain reaction (PCR) testing is the gold standard for determining the HIV status in children <18 months of age. However, when clinical manifestations are not consistent with laboratory results, additional investigation is required. We report a 15-month-old HIV-exposed boy referred to our hospital after he had been admitted several times for infectious diseases. A rapid antibody test on the child was positive, while routine diagnostic HIV PCRs using the Roche COBAS Ampliprep/COBAS TaqMan HIV Qual Test were negative at 6 weeks, 6 months, 7 months and 15 months. In addition, the same PCR test performed on the HIV-infected mother was also negative. Alternative PCR and viral load assays using different primer sets detected HIV RNA or proviral DNA in both child and mother. Gag sequences from the child and his mother classified both infections as HIV-1 subtype C, with very rare mutations that may have resulted in PCR assay primer/probe mismatch. Consequently, the child was commenced on antiretroviral therapy and made a remarkable recovery. These findings indicate that more reliable PCR assays capable of detecting a wide range of HIV subtypes are desirable to circumvent the clinical problems created by false-negative PCR results.

Effect of a probiotic on prevention of diarrhea and Clostridium difficile and Clostridium perfringens shedding in foals.

BACKGROUND: Up to 60% of foals develop diarrhea within 6 months after birth. Preventive measures are limited but potentially probiotics could be used. OBJECTIVE: To evaluate the effect of a newly designed probiotic on the incidence of foal diarrhea in a randomized field trial. ANIMALS: Seventy-two healthy neonatal foals. METHODS: Randomized, placebo-controlled field trial. Foals were administered a placebo or probiotic for 3 weeks and monitored for an additional week. A total of 3 fecal samples were taken from each foal at biweekly intervals. Statistical modeling was applied for comparison of incidence and duration of diarrhea and fecal shedding of Clostridium perfringens and Clostridium difficile between treatment and age groups. RESULTS: The overall incidence of diarrhea was 41 of 72 (59%) and did not differ (P = 0.37) between treatment groups. Foals treated with probiotics were more likely to develop diarrhea requiring veterinary intervention (P = 0.007). Age had a significant effect on incidence of diarrhea (P < 0.001); foals 8-15 days old having the highest probability of developing diarrhea. Duration of diarrhea and soft feces were not significantly different between groups. The prevalence of C. perfringens shedding was 55% with no difference between treatment groups (P = 0.23). The prevalence of C. difficile shedding was 11%. CONCLUSION AND CLINICAL IMPORTANCE: There was no benefit of administering a 3-week course of probiotics, but potential adverse effects were noted. Whether the probiotics lacked a clinical effect, or the choice of strains or dose was inadequate, is unknown. Clostridial shedding was not influenced by probiotics despite in vitro activity of probiotics.

Hypoxic refuges, predator-prey interactions and habitat selection by fishes.

Localized hypoxic habitats were created in Delta Marsh, Manitoba, Canada to determine the potential of regions of moderate hypoxia to act as refuges for forage fishes from piscine predators. Minnow traps and giving-up density (GUD) plates (plexiglas plates covered with trout crumble and fine gravel) were used to assess habitat use and perceived habitat quality for forage fishes, respectively, while passive integrated transponder tags provided data on habitat use by predator species to assess the level of predation risk. Data were collected both before and after a hypoxia manipulation (2-3 mg l(-1) dissolved oxygen, DO) to create a before-after control-effect style experiment. Fathead minnows Pimephales promelas were more abundant and consumed more food from GUD plates in hypoxic bays after the DO manipulation, indicating hypoxic locations were perceived as higher quality, lower-risk habitats. The frequency of predator visits was not consistently affected. The duration of visits, and therefore the total time spent in these habitats, however, was significantly shorter. These predator data, combined with the prey information, are consistent with the hypothesis that hypoxic regions function as predator refuges. The refuge effect is not the result of predator exclusion, however; instead predators are rendered less capable of foraging and pose less of a threat in hypoxic locations.

Gout and hyperuricaemia.

Gout is the most common crystal arthritis and its prevalence is rising. It is associated with the metabolic syndrome, and hyperuricaemia may be an independent risk factor for cardiovascular disease. The acute presentation of gout is easily managed, but the underlying cause is seldom addressed.Indications for initiating uric acid therapy have been clearly established. The classification criteria for gout have been reviewed and are presented here.Lifestyle modification is key to the management of gout. The clinician must screen for diabetes, hypertension and hypercholesterolaemia when the diagnosis of gout is made. The management of asymptomatic hyperuricaemia is still being researched. As yet, there is no indication to start urate-lowering therapy in such patients. Allopurinol remains the first line of treatment, but there are newer drugs being researched in various clinical trials. Probenecid is the alternative in patients with preserved renal function, who do not have a history of renal calculi.

Adaptive changes in HIV-1 subtype C proteins during early infection are driven by changes in HLA-associated immune pressure.

It is unresolved whether recently transmitted human immunodeficiency viruses (HIV) have genetic features that specifically favour their transmissibility. To identify potential "transmission signatures", we compared 20 full-length HIV-1 subtype C genomes from primary infections, with 66 sampled from ethnically and geographically matched individuals with chronic infections. Controlling for recombination and phylogenetic relatedness, we identified 39 sites at which amino acid frequency spectra differed significantly between groups. These sites were predominantly located within Env, Pol and Gag (14/39, 9/39 and 6/39 respectively) and were significantly clustered (33/39) within known immunoreactive peptides. Within 6 months of infection, we detected reversion-to-consensus mutations at 14 sites and potential CTL escape mutations at seven. Here we provide evidence that frequent reversion mutations probably allows the virus to recover replicative fitness which, together with immune escape driven by the HLA alleles of the new hosts, differentiate sequences from chronic infections from those sampled shortly after transmission.

Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-poisson distribution of transmitted variants.

Identifying the specific genetic characteristics of successfully transmitted variants may prove central to the development of effective vaccine and microbicide interventions. Although human immunodeficiency virus transmission is associated with a population bottleneck, the extent to which different factors influence the diversity of transmitted viruses is unclear. We estimate here the number of transmitted variants in 69 heterosexual men and women with primary subtype C infections. From 1,505 env sequences obtained using a single genome amplification approach we show that 78% of infections involved single variant transmission and 22% involved multiple variant transmissions (median of 3). We found evidence for mutations selected for cytotoxic-T-lymphocyte or antibody escape and a high prevalence of recombination in individuals infected with multiple variants representing another potential escape pathway in these individuals. In a combined analysis of 171 subtype B and C transmission events, we found that infection with more than one variant does not follow a Poisson distribution, indicating that transmission of individual virions cannot be seen as independent events, each occurring with low probability. While most transmissions resulted from a single infectious unit, multiple variant transmissions represent a significant fraction of transmission events, suggesting that there may be important mechanistic differences between these groups that are not yet understood.

Ultrasound guidance compared with electrical neurostimulation for peripheral nerve block: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Despite the growing interest in the use of ultrasound (US) imaging to guide performance of regional anaesthetic procedures such as peripheral nerve blocks, controversy still exists as to whether US is superior to previously developed nerve localization techniques such as the use of a peripheral nerve stimulator (PNS). We sought to clarify this issue by performing a systematic review and meta-analysis of all randomized controlled trials that have compared these two methods of nerve localization. METHODS: We searched Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and Google Scholar databases and also the reference lists of relevant publications for eligible studies. A total of 13 studies met our criteria and were included for analysis. Studies were rated for methodological quality by two reviewers. Data from these studies were abstracted and synthesized using a meta-analysis. RESULTS: Blocks performed using US guidance were more likely to be successful [risk ratio (RR) for block failure 0.41, 95% confidence interval (CI) 0.26-0.66, P<0.001], took less time to perform (mean 1 min less to perform with US, 95% CI 0.4-1.7 min, P=0.003), had faster onset (29% shorter onset time, 95% CI 45-12%, P=0.001), and had longer duration (mean difference 25% longer, 95% CI 12-38%, P<0.001) than those performed with PNS guidance. US guidance also decreased the risk of vascular puncture during block performance (RR 0.16, 95% CI 0.05-0.47, P=0.001). CONCLUSIONS: US improves efficacy of peripheral nerve block compared with techniques that utilize PNS for nerve localization. Larger studies are needed to determine whether or not the use of US can decrease the number of complications such as nerve injury or systemic local anaesthetic toxicity.

Cohesive social behaviour shortens the stress response: the effects of conspecifics on the stress response in lake sturgeon Acipenser fulvescens.

An examination was made of whether social interactions can have a beneficial effect through the attenuation of the stress response in a social species. In the first experiment, one larger (mean +/-s.e. 194.0 +/- 12.5 g) and seven smaller (32.0 +/- 2.6 g) juvenile lake sturgeon Acipenser fulvescens were placed in tanks to determine whether a classic dominance effect would be established based on body size (n = 6). Large fish did not establish a territory or aggressively interact with smaller fish, as there were no significant differences in nearest-neighbour distances and an absence of aggressive behaviour (biting, chasing and pushing). In the second experiment, it was hypothesized that the presence of conspecifics would have a beneficial effect through an attenuation of the stress response. Fish in groups or isolation were stressed by a brief aerial exposure (30 s), and blood plasma was measured at regular time intervals (0, 20, 40, 60, 120 and 240 min) following the stressor via an implanted cannula (n = 9-11). The presence of conspecifics did not affect the peak cortisol response, however, the overall cortisol response was shorter in duration compared to fish in isolation. Furthermore, secondary stress variables (plasma ions and glucose) showed differences between fish in groups and isolation. The results of these experiments suggest that social interaction plays an important and beneficial role in regulating the stress response in cohesive social species such as A. fulvescens.

Neuraminidase inhibitors for preventing and treating influenza in children.

BACKGROUND: During epidemic years, influenza attack rates in children exceed 40%. Options for prevention and treatment include the neuraminidase inhibitors: zanamivir and oseltamivir. OBJECTIVES: To assess the efficacy, safety and tolerability of neuraminidase inhibitors in the treatment and prevention of influenza infection in children. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005); MEDLINE (1966 to April 2005); EMBASE (January 1980 to December 2004); the on-line GlaxoSmithKline Clinical Trials Register; the on-line Roche Clinical Trial Protocol Registry and Clinical Trial Results Database (August 2005); and reference lists of articles. We also scrutinised web sites of European and US regulatory bodies and contacted manufacturers and authors. SELECTION CRITERIA: Double-blind, randomised, controlled trials comparing neuraminidase inhibitors with placebo or other antiviral drugs in children less than 12 years of age. Additional safety and tolerability data from other sources were also included. DATA COLLECTION AND ANALYSIS: Four authors applied the inclusion criteria to the retrieved studies, assessed trial quality and extracted data. Data were analysed separately for oseltamivir and zanamivir. MAIN RESULTS: Three trials involving 1500 children with a clinical case definition of influenza were included, of whom 977 had laboratory-confirmed influenza. Overall, trial quality was good. Oseltamivir reduced the median duration of illness by 26% (36 hours) in healthy children with laboratory-confirmed influenza (P value less than 0.0001). The reduction was only 7.7% (10 hours) in 'at risk' (asthmatic) children, and this did not reach statistical significance (P value = 0.54). Zanamivir reduced the median duration of illness by 24% (1.25 days) in healthy children with laboratory-confirmed influenza (P value less than 0.001). No data in 'at risk' children were available. Only oseltamivir produced a significant reduction in the complications of influenza (particularly otitis media), although there was a trend to benefit for zanamivir. We identified one randomised, controlled trial of oseltamivir for the prevention of influenza transmission in households, reporting data from 222 paediatric contacts. Where index cases had laboratory-confirmed influenza, a protective efficacy of 55% was observed, but this did not reach statistical significance (P value = 0.089). The adverse events profile of zanamivir was no worse than placebo, but vomiting was more common in children treated with oseltamivir. AUTHORS' CONCLUSIONS: Neuraminidase inhibitors are effective in shortening illness duration in healthy children with influenza, but efficacy in 'at risk' children remains to be proven. Oseltamivir is also effective in reducing the incidence of secondary complications, and may be effective for influenza prophylaxis.

Use of the WHO hemoglobin color scale in family welfare clinics in India.

A situation is reported for the use of the WHO color scale for the measurement of hemoglobin, which was introduced into India in 1996. Charity family welfare clinics held at a medical college hospital in North India offer free sterilization by tubal ligation under local anesthetic to women following a preliminary screening. An obligatory test of the hemoglobin level is required and must be above 7.0 g/dl for the operation. Some clinics attract large numbers, and the card gives a cheap, rapid and reasonably accurate test, adding to the smooth running and reduction of waiting time. It has proved satisfactory over a 2-year period; 2.3% of participants were shown to have a hemoglobin level of 7 g/dl or less.

Neuraminidase inhibitors for preventing and treating influenza in children.

BACKGROUND: During epidemic years, influenza attack rates in children exceed 40%. Options for prevention and treatment include immunisation, amantadine and rimantadine, and the neuraminidase inhibitors: zanamivir and oseltamivir. OBJECTIVES: Our objective was to assess the efficacy, safety and tolerability of neuraminidase inhibitors in the treatment and prophylaxis of influenza infection in children. SEARCH STRATEGY: We searched the Cochrane Acute Respiratory Infections Group Specialised Trials Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and the GlaxoSmithKline Clinical Trials Register, generally from inception through to December 2002. We also screened the references of retrieved articles and scrutinised relevant web sites. We also screened references of retrieved articles and other systematic reviews, scrutinised web sites of European and US regulatory bodies, and contacted manufacturers and authors. SELECTION CRITERIA: Double-blind randomised controlled trials comparing neuraminidase inhibitors with placebo or other antiviral drugs in children less than 12 years of age. Additional safety and tolerability data from other sources were also included. DATA COLLECTION AND ANALYSIS: Four reviewers applied the inclusion criteria to the retrieved studies, assessed trial quality and extracted data. Data were analysed separately for oseltamivir and zanamivir. MAIN RESULTS: We identified three randomised controlled trials reporting data from 1500 children with a clinical case definition of influenza, of whom 798 had laboratory confirmed influenza infection. Two were trials of oseltamivir (in healthy children and in children with asthma) and one was a trial of zanamivir (in healthy children). Overall, trial quality was good. Oseltamivir reduced the median duration of illness by 26% (36 hours) in previously healthy children with laboratory confirmed influenza (p < 0.0001) and by 17% (21 hours) in the intention-to-treat population (p = 0.0002). Zanamivir reduced the median duration of illness by 24% (1.25 days) in previously healthy children with laboratory confirmed influenza (p < 0.001) and by 10% (0.5 days) in the intention-to-treat population (p = 0.011). Both drugs also significantly reduced the time to return to normal activity. Only oseltamivir produced a significant reduction in the complications of influenza (particularly otitis media), although there was a trend to benefit for zanamivir. No data on the use of zanamivir in 'at risk' children were available. The reduction in time to resolution of illness in 'at risk' children (with asthma) treated with oseltamivir was not statistically significant. Although we identified three trials of neuraminidase inhibitors in the prevention of influenza in families (including children), Roche and GlaxoSmithKline were not willing to break-out data for paediatric populations, and so no data were eligible for inclusion in the review. The adverse events profile of zanamivir was no worse than placebo and we found no reports of zanamivir-induced bronchospasm in children. Vomiting was more common in children treated with oseltamivir (p = 0.008), but study withdrawals were similar (<2%) between oseltamivir and placebo. REVIEWER'S CONCLUSIONS: Neuraminidase inhibitors were effective in shortening illness duration and hastening return to normal activity in previously healthy children with a clinical or laboratory diagnosis of influenza. Oseltamivir was effective in reducing the incidence of secondary complications. Efficacy in 'at risk' children remains to be proven. The drugs are safe, but oseltamivir can cause vomiting.

Age and longevity in fish, with consideration of the ferox trout.

In the first part of this paper, we review the evolutionary aspects of age and longevity in fish and then summarize the theory of maturity due to Ray Beverton. This theory allows one to predict age at maturity (and thus a putative point for the onset of senescence) from information on growth rate and mortality rate. We illustrate the application of this theory with data on tilapia species and then discuss the limitations of the theory. In the second part of the paper, we develop an individual based model for the ferox trout. This is a morph of brown trout Salmo salar that is an exception to the common notion that caloric restriction extends lifespan, in the sense that ferox trout achieve long life by eating more, not less. The model allows one to identify the role that ecological and biochemical adaptations play in the longevity of the ferox trout.

Sensory compensation and the detection of predators: the interaction between chemical and visual information.

Recent evidence suggests that environmental conditions may affect whether fishes do or do not respond to the presence of chemical alarm cues in water. We present a simple model which suggests that the combination of risk of predation and information from other sources will determine when fishes should react to these chemical cues. We tested this model with a laboratory experiment which manipulated the risk of predation by altering the animals (hungry or well fed), or their environment (presence or absence of cover). We also altered the availability of visual information by manipulating the water clarity. Consistent with our model, fishes were most likely to react to chemical alarm cues in the absence of visual information and when the perceived risk of predation was high. The manipulation of either parameter was able to extinguish this response.

The effects of human burn injury on urinary nitrate excretion.

Different studies have demonstrated both an increase and a decrease in the biosynthesis of nitric oxide (NO) during the first 2 days following experimental and human burn trauma. This study investigated changes in urinary nitrate excretion in humans following thermal injury in order to determine the temporal relationship between NO release and the initial injury. Urinary nitrate was measured in daily 24-h urine collections taken on days 1-7 following burn injury from 15 patients. The control group consisted of 11 healthy, age- and sex-matched patients who kept a nitrate-restricted diet for five days prior to collection of a single 24-h urine sample. The burns group had a mean age of 41.9 +/- 19.4 (mean +/- S.D.) years and a mean total burn surface area (TBSA) of 30.2 +/- 24.9% (mean +/- S.D.). In the burn injured patients, urinary nitrate levels peaked at day 4 and a 2-fold increase relative to day 1 was observed. Urinary nitrate levels were significantly higher in the burns group than the control group on days 4 and 5 only (p < 0.05 for both days). There was no correlation between TBSA and the measured urinary nitrate levels. This study confirms that the biosynthesis of NO is increased during the first week following burn trauma and establishes that the renal elimination of the by-products of NO metabolism is not increased during the first three days after injury. Notwithstanding the potential effects of burns on nitrate distribution, our findings may reflect a delay in the release of NO following the initial insult.

Intact proprioception and control of labour pain during epidural analgesia.

BACKGROUND: Accurate proprioception is critical while walking, yet an ambulatory epidural regimen that provides adequate analgesia for labour while simultaneously preserving proprioceptive input has not been described. METHODS: Sixty primigravidae in established labour received bupivacaine 15 mg (15 ml of 0.1% w/v) and fentanyl 100 micrograms through a lumbar epidural catheter. Clinical assessment of dorsal column sensory function included: vibration sense, distal proprioception and the Romberg test, and were all performed before catheter insertion and 30 min after the study bolus. Sensory modalities were also tested compared to an unblocked dermatome. Pain was scored on a 0-10 cm visual analogue scale (VAS) before and 30 min after induction. Intensity of the motor block was tested using a modified Bromage score (grade 1-6). RESULTS: The study bolus provided reliable analgesia with 43 parturients attaining a VAS pain score of zero. Mean duration of analgesia was 67.5 min (SD 22.85). All parturients retained the ability to perform a partial knee bend while standing (grade 6). No mothers exhibited impaired distal proprioception, altered vibration sense or a positive Romberg sign. CONCLUSION: This study confirms that the addition of lumbar epidural fentanyl 100 micrograms to 15 mg of epidural bupivacaine provides good control of labour pain with no motor block and establishes that this combination preserves dorsal column sensory function.