Mangarara Formation: exhumed remnants of a middle Miocene, temperate carbonate, submarine channel-fan system on the eastern margin of Taranaki Basin, New Zealand

The middle Miocene Mangarara Formation is a thin (1–60 m), laterally discontinuous unit of moderately to highly calcareous (40–90%) facies of sandy to pure limestone, bioclastic sandstone, and conglomerate that crops out in a few valleys in North Taranaki across the transition from King Country Basin into offshore Taranaki Basin. The unit occurs within hemipelagic (slope) mudstone of Manganui Formation, is stratigraphically associated with redeposited sandstone of Moki Formation, and is overlain by redeposited volcaniclastic sandstone of Mohakatino Formation. The calcareous facies of the Mangarara Formation are interpreted to be mainly mass-emplaced deposits having channelised and sheet-like geometries, sedimentary structures supportive of redeposition, mixed environment fossil associations, and stratigraphic enclosure within bathyal mudrocks and flysch. The carbonate component of the deposits consists mainly of bivalves, larger benthic foraminifers (especially Amphistegina), coralline red algae including rhodoliths (Lithothamnion and Mesophyllum), and bryozoans, a warm-temperate, shallow marine skeletal association. While sediment derivation was partly from an eastern contemporary shelf, the bulk of the skeletal carbonate is inferred to have been sourced from shoal carbonate factories around and upon isolated basement highs (Patea-Tongaporutu High) to the south. The Mangarara sediments were redeposited within slope gullies and broad open submarine channels and lobes in the vicinity of the channel-lobe transition zone of a submarine fan system. Different phases of sediment transport and deposition (lateral-accretion and aggradation stages) are identified in the channel infilling. Dual fan systems likely co-existed, one dominating and predominantly siliciclastic in nature (Moki Formation), and the other infrequent and involving the temperate calcareous deposits of Mangarara Formation. The Mangarara Formation is an outcrop analogue for middle Miocene-age carbonate slope-fan deposits elsewhere in subsurface Taranaki Basin, New Zealand

Optically trapped bacteria pairs reveal discrete motile response to control aggregation upon cell–cell approach

Aggregation of bacteria plays a key role in the formation of many biofilms. The critical first step is cell–cell approach, and yet the ability of bacteria to control the likelihood of aggregation during this primary phase is unknown. Here, we use optical tweezers to measure the force between isolated Bacillus subtilis cells during approach. As we move the bacteria towards each other, cell motility (bacterial swimming) initiates the generation of repulsive forces at bacterial separations of ~3 μm. Moreover, the motile response displays spatial sensitivity with greater cell–cell repulsion evident as inter-bacterial distances decrease. To examine the environmental influence on the inter-bacterial forces, we perform the experiment with bacteria suspended in Tryptic Soy Broth, NaCl solution and deionised water. Our experiments demonstrate that repulsive forces are strongest in systems that inhibit biofilm formation (Tryptic Soy Broth), while attractive forces are weak and rare, even in systems where biofilms develop (NaCl solution). These results reveal that bacteria are able to control the likelihood of aggregation during the approach phase through a discretely modulated motile response. Clearly, the force-generating motility we observe during approach promotes biofilm prevention, rather than biofilm formation

Paracetamol (acetaminophen) or non-steroidal anti-inflammatory drugs, alone or combined, for pain relief in acute otitis media in children

BACKGROUND: Acute otitis media (AOM) is one of the most common childhood infectious diseases and a significant reason for antibiotic prescriptions in children worldwide. Pain from middle ear infection and pressure behind the eardrum is the key symptom of AOM. Ear pain is central to children's and parents' experience of the illness. Because antibiotics provide only marginal benefits, analgesic treatment including paracetamol (acetaminophen) and non-steroidal anti-inflammatory drugs (NSAIDs) is regarded as the cornerstone of AOM management in children. OBJECTIVES: Our primary objective was to assess the effectiveness of paracetamol (acetaminophen) or NSAIDs, alone or combined, compared with placebo or no treatment in relieving pain in children with AOM. Our secondary objective was to assess the effectiveness of NSAIDs compared with paracetamol in children with AOM. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 7, July 2016; MEDLINE (Ovid, from 1946 to August 2016), Embase (from 1947 to August 2016), CINAHL (from 1981 to August 2016), LILACS (from 1982 to August 2016) and Web of Science (from 1955 to August 2016) for published trials. We screened reference lists of included studies and relevant systematic reviews for additional trials. We searched WHO ICTRP, ClinicalTrials.gov, and the Netherlands Trial Registry (NTR) for completed and ongoing trials (search date 19 August 2016). SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the effectiveness of paracetamol or NSAIDs, alone or combined, for pain relief in children with AOM. We also included trials of paracetamol or NSAIDs, alone or combined, for children with fever or upper respiratory tract infections (URTIs) if we were able to extract subgroup data on pain relief in children with AOM either directly or after obtaining additional data from study authors. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed methodological quality of the included trials and extracted data. We used the GRADE approach to rate the overall quality of evidence for each outcome of interest. MAIN RESULTS: We included three RCTs (327 children) which were assessed at low to moderate risk of bias.One RCT included 219 children with AOM, and used a three-arm, parallel group, double-blind design to compare paracetamol versus ibuprofen versus placebo. All children also received antibiotics and those with fever > 39 °C could have received paracetamol (30 mg to 60 mg) additionally to the studied treatments.Another RCT involved 156 febrile children (26 of whom had AOM). The study design was a three-arm, parallel group, double-blind design and compared paracetamol versus ibuprofen versus ibuprofen plus paracetamol.The third RCT included 889 children with respiratory tract infections (82 of whom had AOM). This study applied a 3 x 2 x 2 factorial, open-label design and compared paracetamol versus ibuprofen versus ibuprofen plus paracetamol. Study participants were randomised to one of the three treatment groups as well as two dosing groups (regular versus as required) and two steam inhalation groups (steam versus no steam).Authors of two RCTs provided crude subgroup data on children with AOM. We used data from the remaining trial to inform comparison of paracetamol versus placebo (148 children) and ibuprofen versus placebo (146 children) assessments. Data from all included RCTs informed comparison of ibuprofen versus paracetamol (183 children); data from the two RCTs informed comparison of ibuprofen plus paracetamol versus paracetamol alone (71 children).We found evidence, albeit of low quality, that both paracetamol and ibuprofen as monotherapies were more effective than placebo in relieving pain at 48 hours (paracetamol versus placebo: proportion of children with pain 10% versus 25%, RR 0.38, 95% CI 0.17 to 0.85; number needed to treat to benefit (NNTB) 7; ibuprofen versus placebo: proportion of children with pain 7% versus 25%, RR 0.28, 95% CI 0.11 to 0.70; NNTB 6). Very low quality evidence suggested that adverse events did not significantly differ between children treated with either paracetamol, ibuprofen or placebo.We found insufficient evidence of a difference between ibuprofen and paracetamol in relieving ear pain at 24 hours (2 RCTs, 39 children; RR 0.83, 95% CI 0.59 to 1.18; very low quality evidence), 48 to 72 hours (3 RCTs, 183 children; RR 0.91, 95% CI 0.54 to 1.54; low quality evidence) and four to seven days (2 RCTs, 38 children; RR 0.74, 95% CI 0.17 to 3.23; very low quality evidence).Data on the effectiveness of ibuprofen plus paracetamol versus paracetamol alone came from two RCTs that provided crude subgroup data for 71 children with AOM. The small sample provided imprecise effect estimates and we were consequently unable to draw any firm conclusions (very low quality evidence). AUTHORS' CONCLUSIONS: Despite explicit guideline recommendations on its use, current evidence on the effectiveness of paracetamol or NSAIDs, alone or combined, in relieving pain in children with AOM is limited. Low quality evidence indicates that both paracetamol and ibuprofen as monotherapies are more effective than placebo in relieving short-term ear pain in children with AOM. There is insufficient evidence of a difference between ibuprofen and paracetamol in relieving short-term ear pain in children with AOM, whereas data on the effectiveness of ibuprofen plus paracetamol versus paracetamol alone were insufficient to draw any firm conclusions. Further research is needed to provide insights into the role of ibuprofen as adjunct to paracetamol, and other analgesics such as anaesthetic eardrops, for children with AOM

Corticosteroid injection for tennis elbow or lateral epicondylitis: a review of the literature

Lateral epicondylitis or tennis elbow is a painful and functionally limiting entity affecting the upperextremity and is frequently treated by hand surgeons. Corticosteroid injection is one of the most common interventions for lateral epicondylitis or tennis elbow. Here, a review of the medical literature on this treatment is presented

The global distribution and burden of dengue.

Dengue is a systemic viral infection transmitted between humans by Aedes mosquitoes. For some patients, dengue is a life-threatening illness. There are currently no licensed vaccines or specific therapeutics, and substantial vector control efforts have not stopped its rapid emergence and global spread. The contemporary worldwide distribution of the risk of dengue virus infection and its public health burden are poorly known. Here we undertake an exhaustive assembly of known records of dengue occurrence worldwide, and use a formal modelling framework to map the global distribution of dengue risk. We then pair the resulting risk map with detailed longitudinal information from dengue cohort studies and population surfaces to infer the public health burden of dengue in 2010. We predict dengue to be ubiquitous throughout the tropics, with local spatial variations in risk influenced strongly by rainfall, temperature and the degree of urbanization. Using cartographic approaches, we estimate there to be 390 million (95% credible interval 284-528) dengue infections per year, of which 96 million (67-136) manifest apparently (any level of disease severity). This infection total is more than three times the dengue burden estimate of the World Health Organization. Stratification of our estimates by country allows comparison with national dengue reporting, after taking into account the probability of an apparent infection being formally reported. The most notable differences are discussed. These new risk maps and infection estimates provide novel insights into the global, regional and national public health burden imposed by dengue. We anticipate that they will provide a starting point for a wider discussion about the global impact of this disease and will help to guide improvements in disease control strategies using vaccine, drug and vector control methods, and in their economic evaluation

Excretion of catecholamines in rats, mice and chicken

Stress assessment favours methods, which do not interfere with an animal’s endocrine status. To develop such non-invasive methods, detailed knowledge about the excretion of hormone metabolites in the faeces and urine is necessary. Our study was therefore designed to generate basic information about catecholamine excretion in rats, mice and chickens. After administration of 3H-epinephrine or 3H-norepinephrine to male and female rats, mice and chickens, all voided excreta were collected for 4 weeks, 3 weeks or for 10 days, respectively. Peak concentrations of radioactivity appeared in one of the first urinary samples of mice and rats and in the first droppings in chickens 0.2–7.2 h after injection. In rats, between 77.3 and 95.6% of the recovered catecholamine metabolites were found in the urine, while in mice, a mean of 76.3% were excreted in the urine. Peak concentrations in the faeces were found 7.4 h post injection in mice, and after about 16.4 h in rats (means). Our study provides valuable data about the route and the profile of catecholamine excretion in three frequently used species of laboratory animals. This represents the first step in the development of a reliable, non-invasive quantification of epinephrine and norepinephrine to monitor sympatho-adrenomedullary activity, although promising results for the development of a non-invasive method were found only for the chicken

Phosphoenolpyruvate carboxylase dentified as a key enzyme in erythrocytic Plasmodium falciparum carbon metabolism

Phospoenolpyruvate carboxylase (PEPC) is absent from humans but encoded in thePlasmodium falciparum genome, suggesting that PEPC has a parasite-specific function. To investigate its importance in P. falciparum, we generated a pepc null mutant (D10Δpepc), which was only achievable when malate, a reduction product of oxaloacetate, was added to the growth medium. D10Δpepc had a severe growth defect in vitro, which was partially reversed by addition of malate or fumarate, suggesting that pepc may be essential in vivo. Targeted metabolomics using 13C-U-D-glucose and 13C-bicarbonate showed that the conversion of glycolytically-derived PEP into malate, fumarate, aspartate and citrate was abolished in D10Δpepc and that pentose phosphate pathway metabolites and glycerol 3-phosphate were present at increased levels. In contrast, metabolism of the carbon skeleton of 13C,15N-U-glutamine was similar in both parasite lines, although the flux was lower in D10Δpepc; it also confirmed the operation of a complete forward TCA cycle in the wild type parasite. Overall, these data confirm the CO2 fixing activity of PEPC and suggest that it provides metabolites essential for TCA cycle anaplerosis and the maintenance of cytosolic and mitochondrial redox balance. Moreover, these findings imply that PEPC may be an exploitable target for future drug discovery

Behavioral changes in Rattus norvegicus experimentally infected by Toxocara canis larvae

Toxocara canis is a common canine nematode parasite and one of its possible transmission mechanisms is the predation of infected rodents by canids. Fifty Rattus norvegicus were used to study behavioral alterations in rodents infected by T. canis larvae. The rats were divided into three groups: G1, 20 rats infected with 300 T. canis eggs; G2, 20 rats infected with 2,000 T. canis eggs; and G3, 10 non-infected rats. Thirty and 60 days post-infection, rats from all the groups were submitted to an open-field apparatus for five min and subsequently, to an elevated plus-maze apparatus, again for five min. The data obtained indicated improvement in mobility (total locomotion time and rearing frequency) and exploratory behavior in infected rats, principally in G2, which provides some support for the hypothesis that behavioral alterations in rodents infected by Toxocara canis larvae enhance the transmission rate of this ascarid to dogs.Toxocara canis é um nematódeo parasita habitual do intestino delgado de cães. Um dos mecanismos conhecidos de transmissão para cães é representado pela predação de pequenos roedores que, como hospedeiros paratênicos albergam larvas de Toxocara canis em seus tecidos. Para avaliar a ocorrência de alterações de comportamento em roedores infectados por Toxocara canis 50 exemplares de Rattus norvegicus foram utilizados no experimento. Os animais foram divididos em três grupos: G1 - 20 ratos infectados com 300 ovos de Toxocara canis; G2 - 20 ratos infectados com 2.000 ovos de Toxocara canis e G3 - 10 ratos sem infecção. Trinta e 60 dias após a infecção avaliou-se a ocorrência de alterações comportamentais nos três grupos submetendo os animais, primeiramente, a uma arena de campo aberto durante cinco minutos e, a seguir, a labirinto em cruz elevado por mais cinco minutos. Os resultados obtidos indicaram aumento significativo da mobilidade (tempo total de movimentação e número de vezes em que os animais se levantaram nas patas traseiras) e comportamento exploratório nos ratos infectados, principalmente nos pertencentes ao G2, sugerindo a ocorrência de alterações comportamentais que favoreceriam a transmissão de Toxocara canis para canídeos por meio de relação presa-predador

Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data