Understanding global influenza migration and persistence is crucial for vaccine strain selection. Using 240 new human influenza A virus whole genomes collected in Vietnam during 2001–2008, we looked for persistence patterns and migratory connections between Vietnam and other countries. We found that viruses in Vietnam migrate to and from China, Hong Kong, Taiwan, Cambodia, Japan, South Korea, and the United States. We attempted to reduce geographic bias by generating phylogenies subsampled at the year and country levels. However, migration events in these phylogenies were still driven by the presence or absence of sequence data, indicating that an epidemiologic study design that controls for prevalence is required for robust migration analysis. With whole-genome data, most migration events are not detectable from the phylogeny of the hemagglutinin segment alone, although general migratory relationships between Vietnam and other countries are visible in the hemagglutinin phylogeny. It is possible that virus lineages in Vietnam persisted for >1 year.
influenza; tropics; migration; persistence; phylogeography; viruses; Vietnam
Otosclerosis is a disease of abnormal bone remodeling in the otic capsule. Although several drugs that inhibit bone remodeling, including sodium fluoride and first generation bisphosphonates, have been tried, there remains no clearly effective treatment for otosclerosis-related sensorineural hearing loss (SNHL). Over the past several years, third generation bisphosphonates, with more powerful anti-resorptive properties and increased bone affinity, have been developed and have demonstrated effectiveness in the treatment of osteoporosis and other metabolic bone diseases. We hypothesized that newer generation bisphosphonates, such as risedronate and zoledronate, would be effective in slowing the progression of SNHL in patients with otosclerosis.
Tertiary referral center, ambulatory care
Risedronate or zoledronate administration
Main outcome measures
Bone conduction pure tone threshold averages (PTA) and word recognition (WR) scores were examined for each ear before and after bisphosphonate treatment. Criteria for significant change were defined as greater than 10 decibels in PTA or between 4 to 18% in WR based on binomial variance.
All 10 patients had audiometric progression of SNHL in the pre-treatment monitoring interval and 12 ears met criteria for significant progression. All 10 patients (19 ears) showed at least no significant progression of SNHL (i.e. stabilization) at an average follow up of 13 months. Two patients (3 ears) showed improvement by defined audiometric criteria. There were no major complications.
Treatment with zoledronate or risedronate stabilized progressive SNHL related to otosclerosis in this small group of patients. Further evaluation of third generation bisphosphonate treatments is warranted.
Aposematic prey warn predators of their toxicity using conspicuous signals. However, predators regularly include aposematic prey in their diets, particularly when they are in a poor energetic state and in need of nutrients. We investigated whether or not an environmental factor, ambient temperature, could change the energetic state of predators and lead to an increased intake of prey that they know to contain toxins. We found that European starlings, Sturnus vulgaris, increased their consumption of mealworm, Tenebrio molitor, prey containing quinine (a mild toxin) when the ambient temperature was reduced below their thermoneutral zone from 20 °C to 6 °C. The birds differed in their sensitivity to changes in ambient temperature, with heavier birds increasing the number of toxic prey they ate more rapidly with decreasing temperature compared to birds with lower body mass. This could have been the result of their requiring more nutrients at lower temperatures or being better able to detoxify quinine. Taken together, our results suggest that conspicuous coloration may be more costly at lower temperatures, and that aposematic prey may need to invest more in chemical defences as temperatures decline. Our study also provides novel insights into what factors affect birds' decisions to eat toxic prey, and demonstrates that selection pressures acting on prey defences can vary with changing temperature across days, seasons, climes, and potentially in response to climate change.
•We investigated the effect of temperature on birds' decisions to eat toxic prey.•As it got cooler, birds were more likely to eat prey containing toxins.•Heavier birds were more sensitive to changes in temperature.•Selection pressures on prey defences will change over days, seasons and climes.
aposematism; decision making; dietary cognition; mimicry; nutrient–toxin trade-off; state-dependent foraging
A newly produced murine recombinant ACE2 was characterized in vivo and in vitro. The effects of available ACE2 inhibitors (MLN-4760 and two conformational variants of DX600 –linear and cyclic) were also examined. When murine ACE2 was given to mice for 4 weeks, a marked increase in serum ACE2 activity was sustainable. In acute studies, mouse ACE2 (1mg/kg) obliterated hypertension induced by angiotensin II infusion by rapidly decreasing plasma angiotensin II. These effects were blocked by MLN-4760 but not by either form of DX600. In vitro, conversion from angiotensin II to angiotensin-(1–7) by mouse ACE2 was blocked by MLN-4760 (10−6M) but not by either form of DX600 (10−5M). Quantitative analysis of multiple angiotensin peptides in plasma ex vivo revealed formation of angiotensin-(1–9) from angiotensin I by human but not by mouse ACE2. Both human and mouse ACE2 led to the dissipation of angiotensin II with formation of angiotensin-(1–7). By contrast, mouse ACE2-driven angiotensin-(1–7) formation from angiotensin II was blocked by MLN-4760 but not by either linear or cyclic DX600.
In conclusion, sustained elevations in serum ACE2 activity can be accomplished with murine ACE2 administration thereby providing a strategy for ACE2 amplification in chronic studies using rodent models of hypertension and cardiovascular disease. Human, but not mouse ACE2, degrades angiotensin I to form angiotensin-(1–9). There are also species differences regarding rodent and human ACE2 inhibition by known inhibitors such that MLN-4760 inhibits both human and mouse ACE2 whereas DX600 only blocks human ACE2 activity.
ACE2; Recombinant; Mouse; Human; Hypertension; Angiotensin; Inhibitor
Wild birds have been implicated in the emergence of human and livestock influenza. The successful prediction of viral spread and disease emergence, as well as formulation of preparedness plans have been hampered by a critical lack of knowledge of viral movements between different host populations. The patterns of viral spread and subsequent risk posed by wild bird viruses therefore remain unpredictable. Here we analyze genomic data, including 287 newly sequenced avian influenza A virus (AIV) samples isolated over a 34-year period of continuous systematic surveillance of North American migratory birds. We use a Bayesian statistical framework to test hypotheses of viral migration, population structure and patterns of genetic reassortment. Our results reveal that despite the high prevalence of Charadriiformes infected in Delaware Bay this host population does not appear to significantly contribute to the North American AIV diversity sampled in Anseriformes. In contrast, influenza viruses sampled from Anseriformes in Alberta are representative of the AIV diversity circulating in North American Anseriformes. While AIV may be restricted to specific migratory flyways over short time frames, our large-scale analysis showed that the long-term persistence of AIV was independent of bird flyways with migration between populations throughout North America. Analysis of long-term surveillance data provides vital insights to develop appropriately informed predictive models critical for pandemic preparedness and livestock protection.
Despite continuous virological surveillance (1976–2009) in wild waterfowl (Anseriformes) and shorebirds (Charadriiformes), the ecological and evolutionary dynamics of avian influenza A virus (AIV) in these hosts is poorly understood. Comparative genomic analysis of AIV data revealed that the high prevalence of Charadriiformes infected in Delaware Bay is a reservoir of AIV that is phylogenetically distinct from AIV sampled from most North American Anseriformes. In contrast, influenza viruses sampled from Anseriformes in Alberta are representative of the remaining AIV diversity sampled across North America. While AIV may be restricted to specific migratory flyways over short time frames, our large-scale analysis showed that this population genetic structure was transient and the long-term persistence of AIV was independent of bird flyways. These results suggest an introduced virus lineage may initially be restricted to one flyway, but migration to a major congregation site such as Alberta could occur followed by subsequent spread across flyways. These generalized predictions for virus movement will be critical to assess the associated risk for widespread diffusion and inform surveillance for pandemic preparedness.
To report the pre- and post treatment population characteristics, and the overall stability of the audiologic outcomes found during the Sudden Hearing Loss Clinical Trial [ClinicalTrials.gov: Identifier NCT00097448].
Multi-center, prospective randomized non-inferiority trial of oral v. intratympanic (IT) steroid treatment of sudden sensorineural hearing loss (SSNHL).
Fifteen academically-based otology practices
250 patients with unilateral SSNHL presenting within 14 days of onset with ≥50 dBHL pure tone average hearing threshold in the affected ear.
Either 60 mg/day oral prednisone for 14 days with a 5-day taper (121 patients) or four IT doses over 14 days of 40mg/ml methylprednisolone (129 patients).
Main Outcome Measure
Primary endpoint was change in hearing [dB PTA] at 2 months after treatment. Non-inferiority was defined as <10 dB difference in hearing outcome between treatments. In this article, pre- and post treatment hearing findings will be reported in detail.
A general (and stable) effect of treatment, and a specific effect of greater improvement at low frequencies was found in both treatment groups.
Hearing improvements are stable and a significantly greater improvement occurs wit lower frequency following either oral or IT steroid treatment of SSNHL.
We report the complete genome sequence of a reassortant H14N2 avian influenza virus isolated in 2011 from a northern shoveler in California. This introduced Eurasian subtype acquired seven segments from North American viruses and circulated in the Pacific Flyway 1 year after its detection in the Mississippi Flyway.
We aimed to determine whether amyloid imaging can help predict the location and number of future hemorrhages in cerebral amyloid angiopathy (CAA).
We performed a longitudinal cohort study of 11 patients with CAA without dementia who underwent serial brain MRIs after baseline amyloid imaging with Pittsburgh compound B (PiB). Mean distribution volume ratio (DVR) of PiB was determined at the sites of new micro/macrobleeds identified on follow-up MRI and compared with PiB retention at “simulated” hemorrhages, randomly placed in the same subjects using a probability distribution map of CAA-hemorrhage location. Mean PiB retention at the sites of observed new bleeds was also compared to that in shells concentrically surrounding the bleeds. Finally the association between number of incident bleeds and 3 regional amyloid measures were obtained.
Nine of 11 subjects had at least one new microbleed on follow-up MRI (median 4, interquartile range [IQR] 1–9) and 2 had 5 new intracerebral hemorrhages. Mean DVR was greater at the sites of incident bleeds (1.34, 95% confidence interval [CI] 1.23–1.46) than simulated lesions (1.14, 95% CI 1.07–1.22, p < 0.0001) in multivariable models. PiB retention decreased with increasing distance from sites of observed bleeds (p < 0.0001). Mean DVR in a superior frontal/parasagittal region of interest correlated independently with number of future hemorrhages after adjustment for relevant covariates (p = 0.003).
Our results provide direct evidence that new CAA-related hemorrhages occur preferentially at sites of increased amyloid deposition and suggest that PiB-PET imaging may be a useful tool in prediction of incident hemorrhages in patients with CAA.
In addition to its role in hemorrhagic stroke, advanced cerebral amyloid angiopathy (CAA) is also associated with ischemic lesions and vascular cognitive impairment. We used functional MRI techniques to identify CAA-associated vascular dysfunction.
Functional MRI was performed on 25 nondemented subjects with probable CAA (mean ± standard deviation age 70.2±7.8) and 12 healthy elderly controls (age 75.3±6.2). Parameters measured were reactivity to visual stimulation (quantified as blood oxygen level-dependent [BOLD] response amplitude, time to peak response, and time to return to baseline after stimulus cessation) and resting absolute cerebral blood flow in the visually activated region (measured by arterial spin labeling).
CAA subjects demonstrated reduced response amplitude (percent change in BOLD signal 0.65±0.28 vs 0.89±0.14, p<0.01), prolonged time to peak (11.1±5.1 vs 6.4±1.8 sec, p<0.001) and prolonged time to baseline (16.5±6.7 vs 11.6±3.1 sec, p<0.001) relative to controls. These differences were independent of age, sex, and hypertension in multivariable analysis and were also present in secondary analyses excluding nonresponsive voxels or voxels containing chronic blood products. Within the CAA group, longer time to peak correlated with overall volume of white matter T2 hyperintensity (Pearson correlation 0.53, p=0.007). Absolute resting blood flow in visual cortex, in contrast, was essentially identical between the groups (44.0±12.6 vs 45.0±10.0 ml/100g/min, p=0.8).
Functional MRI identifies robust differences in both amplitude and timing of the response to visual stimulation in advanced CAA. These findings point to potentially powerful approaches for identifying the mechanistic links between vascular amyloid deposits, vascular dysfunction, and CAA-related brain injury.
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine and a selective inducer of apoptosis in a range of tumour cells, but not in normal, untransformed cells. A large number of chemotherapeutics as well as biological agents are being tested for their potential to sensitise resistant tumour cells to TRAIL as a means to broaden the range of tumours treatable with TRAIL. However, because of the incomplete understanding of the mechanism(s) underlying TRAIL resistance in non-malignant cells, it is unpredictable whether the effect of these sensitisers will be restricted to tumour cells or they would also sensitise non-transformed cells causing unwanted toxicity. In this study, we carried out a systematic analysis of the mechanisms driving TRAIL resistance in non-transformed cells. We found that cellular FLICE-like inhibitory protein, anti-apoptotic B-cell lymphoma 2 proteins, and X-linked inhibitor of apoptosis protein were independently able to provide resistance to TRAIL. Deficiency of only one of these proteins was not sufficient to elicit TRAIL sensitivity, demonstrating that in non-transformed cells multiple pathways control TRAIL resistance and they act in a redundant manner. This is contrary to the resistance mechanisms found in tumour cell types, many of them tend to rely on a single mechanism of resistance. Supporting this notion we found that 76% of TRAIL-resistant cell lines (13 out of 17) expressed only one of the above-identified anti-apoptotic proteins at a high level (≥1.2-fold higher than the mean expression across all cell lines). Furthermore, inhibition or knockdown of the single overexpressed protein in these tumour cells was sufficient to trigger TRAIL sensitivity. Therefore, the redundancy in resistance pathways in non-transformed cells may offer a safe therapeutic window for TRAIL-based combination therapies where selective sensitisation of the tumour to TRAIL can be achieved by targeting the single non-redundant resistance pathway.
non-transformed primary cells; TRAIL; apoptosis; c-FLIP; XIAP; Bcl-2
Human influenza virus isolates generally grow poorly in embryonated chicken eggs. Hence, gene reassortment of influenza A wild type (wt) viruses is performed with a highly egg adapted donor virus, A/Puerto Rico/8/1934 (PR8), to provide the high yield reassortant (HYR) viral ‘seeds’ for vaccine production. HYR must contain the hemagglutinin (HA) and neuraminidase (NA) genes of wt virus and one to six ‘internal’ genes from PR8. Most studies of influenza wt and HYRs have focused on the HA gene. The main objective of this study is the identification of the molecular signature in all eight gene segments of influenza A HYR candidate vaccine seeds associated with high growth in ovo.
The genomes of 14 wt parental viruses, 23 HYRs (5 H1N1; 2, 1976 H1N1-SOIV; 2, 2009 H1N1pdm; 2 H2N2 and 12 H3N2) and PR8 were sequenced using the high-throughput sequencing pipeline with big dye terminator chemistry.
Silent and coding mutations were found in all internal genes derived from PR8 with the exception of the M gene. The M gene derived from PR8 was invariant in all 23 HYRs underlining the critical role of PR8 M in high yield phenotype. None of the wt virus derived internal genes had any silent change(s) except the PB1 gene in X-157. The highest number of recurrent silent and coding mutations was found in NS. With respect to the surface antigens, the majority of HYRs had coding mutations in HA; only 2 HYRs had coding mutations in NA.
In the era of application of reverse genetics to alter influenza A virus genomes, the mutations identified in the HYR gene segments associated with high growth in ovo may be of great practical benefit to modify PR8 and/or wt virus gene sequences for improved growth of vaccine ‘seed’ viruses.
This article reports the characterization of thin SiGe/Si(100) epilayers using reciprocal space maps measured by a laboratory X-ray instrument and a high-resolution X-ray diffraction study of partially relaxed SiGe/Si thin films.
The technique of reciprocal space mapping using X-rays is a recognized tool for the nondestructive characterization of epitaxial films. X-ray scattering from epitaxial Si0.4Ge0.6 films on Si(100) substrates using a laboratory X-ray source was investigated. It is shown that a laboratory source with a rotating anode makes it possible to investigate the material parameters of the super-thin 2–6 nm layers. For another set of partially relaxed layers, 50–200 nm thick, it is shown that from a high-resolution reciprocal space map, conditioned from diffuse scattering on dislocations, it is possible to determine quantitatively from the shape of a diffraction peak (possessing no thickness fringes) additional parameters such as misfit dislocation density and layer thickness as well as concentration and relaxation.
thin films; high-resolution reciprocal space mapping; partly relaxed epitaxial films; misfit dislocation
The role of gulls in the ecology of avian influenza (AI) is different than that of waterfowl. Different constellations of subtypes circulate within the two groups of birds and AI viruses isolated from North American gulls frequently possess reassortant genomes with genetic elements from both North America and Eurasian lineages. A 2008 isolate from a Newfoundland Great Black-backed Gull contained a mix of North American waterfowl, North American gull and Eurasian lineage genes.
We isolated, sequenced and phylogenetically compared avian influenza viruses from 2009 Canadian wild birds.
We analyzed six 2009 virus isolates from Canada and found the same phylogenetic lineage had persisted over a larger geographic area, with an expanded host range that included dabbling and diving ducks as well as gulls. All of the 2009 virus isolates contained an internal protein coding set of genes of the same Eurasian lineage genes except PB1 that was from a North American lineage, and these genes continued to evolve by genetic drift. We show evidence that the 2008 Great Black-backed Gull virus was derived from this lineage with a reassortment of a North American PA gene into the more stable core set of internal protein coding genes that has circulated in avian populations for at least 2 years. From this core, the surface glycoprotein genes have switched several times creating H13N6, H13N2, and H16N3 subtypes. These gene segments were from North American lineages except for the H16 and N3 vRNAs.
This process appears similar to genetic shifts seen with swine influenza where a stable “triple reassortant internal gene” core has circulated in swine populations with genetic shifts occurring with hemaggluttinin and neuraminidase proteins getting periodically switched. Thus gulls may serve as genetic mixing vessels for different lineages of avian influenza, similar to the role of swine with regards to human influenza. These findings illustrate the need for continued surveillance in gull and waterfowl populations, both on the Pacific and especially Atlantic coasts of North America, to document virus intercontinental movement and the role of gull species in the evolution and epidemiology of AI.
According to the Kauffmann-White scheme, 39 pairs of serovars in Salmonella serogroup C2 differ only by the minor antigen O:61. We characterized strains from 10 serovars representing five Salmonella serogroup C2 pairs. All strains demonstrated variable expression of O:61. These results indicate that these pairs are not distinct serovars.
Predators that have learned to associate warning coloration with toxicity often continue to include aposematic prey in their diet in order to gain the nutrients and energy that they contain. As body size is widely reported to correlate with energetic content, we predicted that prey size would affect predators' decisions to eat aposematic prey. We used a well-established system of wild-caught European starlings, Sturnus vulgaris, foraging on mealworms, Tenebrio molitor, to test how the size of undefended (water-injected) and defended (quinine-injected) prey, on different coloured backgrounds, affected birds’ decisions to eat defended prey. We found that birds ate fewer defended prey, and less quinine, when undefended prey were large compared with when they were small, but that the size of the defended prey had no effect on the numbers eaten. Consequently, we found no evidence that the mass of the defended prey or the overall mass of prey ingested affected the amount of toxin that a predator was willing to ingest, and instead the mass of undefended prey eaten was more important. This is a surprising finding, challenging the assumptions of state-dependent models of aposematism and mimicry, and highlighting the need to understand better the mechanisms of predator decision making. In addition, the birds did not learn to discriminate visually between defended and undefended prey based on size, but only on the basis of colour. This suggests that colour signals may be more salient to predators than size differences, allowing Batesian mimics to benefit from aposematic models even when they differ in size.
•The size of toxic prey did not affect the amount of toxin ingested by birds.•Total prey mass eaten did not affect the amount of toxin ingested by birds.•The amount of toxin ingested by birds depended on the mass of nontoxic prey.•Colour signals may be more salient to predators than size differences.•Findings have implications for the selection pressures acting on aposematic prey.
aposematism; educated predator; energy; European starling; foraging; mimicry; prey size; Sturnus vulgaris; toxic prey
Despite the importance of migratory birds in the ecology and evolution of avian influenza virus (AIV), there is a lack of information on the patterns of AIV spread at the intra-continental scale. We applied a variety of statistical phylogeographic techniques to a plethora of viral genome sequence data to determine the strength, pattern, and determinants of gene flow in AIV sampled from wild birds in North America. These analyses revealed a clear isolation-by-distance of AIV among sampling localities. In addition, we show that phylogeographic models incorporating information on the avian flyway of sampling proved a better fit to the observed sequence data than those specifying homogeneous or random rates of gene flow among localities. In sum, these data strongly suggest that the intra-continental spread of AIV by migratory birds is subject to major ecological barriers, including spatial distance and avian flyway.
avian influenza; phylogeography; evolution; gene flow; ecological barriers; flyways; spatial distance
When novel influenza viruses cause human infections, it is critical to characterize the illnesses, viruses, and immune responses to infection in order to develop diagnostics, treatments, and vaccines. The objective of the study was to collect samples from patients with suspected or confirmed A(H1N1)pdm09 infections that could be made available to the scientific community. Respiratory secretions, sera and peripheral blood mononuclear cells (PBMCs) were collected sequentially (when possible) from patients presenting with suspected or previously confirmed A(H1N1)pdm09 infections. Clinical manifestations and illness outcomes were assessed. Respiratory secretions were tested for the presence of A(H1N1)pdm09 virus by means of isolation in tissue culture and real time RT-PCR. Sera were tested for the presence and level of HAI and neutralizing antibodies against the A(H1N1)pdm09 virus.
Findings and conclusions
Thirty patients with confirmed A(H1N1)pdm09 infection were enrolled at Baylor College of Medicine (BCM). Clinical manifestations of illness were consistent with typical influenza. Twenty-eight of 30 had virological confirmation of illness; all recovered fully. Most patients had serum antibody responses or high levels of antibody in convalescent samples. Virus-positive samples were sent to J. Craig Venter Institute for sequencing and sequences were deposited in GenBank. Large volumes of sera collected from 2 convalescent adults were used to standardize antibody assays; aliquots of these sera are available from the repository. Aliquots of serum, PBMCs and stool collected from BCM subjects and subjects enrolled at other study sites are available for use by the scientific community, upon request.
2009 H1N1 virus; Immune responses; Influenza
viruses; henipavirus; pteropid bats; fruit bats; Papua New Guinea; emerging disease; Hendra; Nipah; bat; Australia
The routes of henipavirus transmission between hosts are poorly understood. The purpose of this study was to measure the persistence of henipaviruses under various environmental conditions and thereby gain an insight into likely mechanisms of transmission. Henipaviruses survived for more than four days at 22°C in pH-neutral fruit bat urine but were sensitive to higher temperatures and pH changes. On mango flesh, survival time varied depending on temperature and fruit pH, ranging from two hours to more than two days. Desiccation of viruses substantially reduced survival time to less than two hours. The sensitivity of henipaviruses to pH, temperature and desiccation indicates a need for close contact between hosts for transmission to occur, although under ideal conditions henipaviruses can persist for extended periods facilitating vehicle-borne transmission.
Paramyxovirus; Hendra virus; Nipah virus; Henipavirus; Virology; Dessication; Urine; Fruit; Temperature; Transmission
Ammonia is metabolized by the liver and has established neurological effects. The current study examined the possibility that ammonia contributes to the neurotoxic effects of methamphetamine (METH). The results show that a binge dosing regimen of METH to the rat increased plasma and brain ammonia concentrations that were paralleled by evidence of hepatotoxicity. The role of peripheral ammonia in the neurotoxic effects of METH was further substantiated by the demonstration that the enhancement of peripheral ammonia excretion blocked the increases in brain and plasma ammonia and attenuated the long term depletions of dopamine and serotonin typically produced by METH. Conversely, the localized perfusion of ammonia in combination with METH, but not METH alone or ammonia alone, into the striatum recapitulated the neuronal damage produced by the systemic administration of METH. Furthermore, this damage produced by the local administration of ammonia and METH was blocked by the GYKI 52466, an AMPA receptor antagonist. These findings highlight the importance of ammonia derived from the periphery as a small molecule mediator of METH neurotoxicity and more broadly emphasize the importance of peripheral organ damage as a possible mechanism that mediates the neuropathology produced by drugs of abuse and other neuroactive molecules.
AIM: To suggest infliximab (IFX) is effective for acute severe ulcerative colitis, from real-life clinical practice.
METHODS: All patients receiving IFX for the treatment of acute severe ulcerative colitis in a single centre were included. Data were extracted from clinical records in order to assess response to IFX therapy. The primary endpoint was colectomy-free survival, and secondary outcomes included glucocorticosteroid-free remission and safety, which was evaluated by recording deaths and adverse events. Demographic and clinical characteristics of those who underwent colectomy and those who were colectomy-free, both at discharge from their index admission, and during follow-up after an initial response to IFX were compared.
RESULTS: Forty-four patients (16 females, mean age 36 years) received IFX between May 2006 and January 2012 for acute severe ulcerative colitis. The median duration of follow-up post-first infusion was 396 d (interquartile range = 173-828 d). There were 21 (47.7%) patients with < 1 year of follow-up, 10 (22.7%) with 1 years to 2 years of follow-up, and 13 (29.5%) with > 2 years of follow-up post-first infusion of IFX. Overall, 35 (79.5%) responded to IFX, avoiding colectomy during their index admission, 29 (65.9%) were colectomy-free at last point of follow-up (median follow-up 396 d), and 25 (56.8%) were in glucocorticosteroid-free remission at end of follow-up. There was one death from post-operative sepsis, 20 d after a single IFX infusion. Colectomy rates were generally lower among those “bridging” to thiopurine. Of 18 patients “bridged” to thiopurine therapy, 17 (94.4%) were colectomy-free, and 15 (83.3%) were in glucocorticosteroid-free remission at study end. No predictors of response were identified.
CONCLUSION: IFX is effective for acute severe ulcerative colitis in real-life clinical practice. Two-thirds of patients avoided colectomy, and more than 50% were in glucocorticosteroid-free remission.
Ulcerative colitis; Severe; Azathioprine; Infliximab; Remission
This study compares measurements of ear-canal reflectance (ECR) to other objective measurements of middle-ear function including, audiometry, umbo velocity (VU), and tympanometry in a population of strictly defined normal hearing ears.
Data were prospectively gathered from 58 ears of 29 normal hearing subjects, 16 female and 13 male, aged 22–64 years. Subjects met all of the following criteria to be considered as having normal hearing. (1) No history of significant middle-ear disease. (2) No history of otologic surgery. (3) Normal tympanic membrane (TM) on otoscopy. (4) Pure-tone audiometric thresholds of 20 dB HL or better for 0.25 – 8 kHz. (5) Air-bone gaps no greater than 15 dB at 0.25 kHz and 10 dB for 0.5 – 4 kHz. (6) Normal, type-A peaked tympanograms. (7) All subjects had two “normal” ears (as defined by these criteria). Measurements included pure-tone audiometry for 0.25 – 8 kHz, standard 226 Hz tympanometry, Ear canal reflectance(ECR) for 0.2 – 6 kHz at 60 dB SPL using the Mimosa Acoustics HearID system, and Umbo Velocity (VU ) for 0.3 – 6 kHz at 70–90 dB SPL using the HLV-1000 laser Doppler vibrometer (Polytec Inc).
Mean power reflectance (|ECR|2) was near 1.0 at 0.2– 0.3 kHz, decreased to a broad minimum of 0.3 to 0.4 between 1 and 4 kHz, and then sharply increased to almost 0.8 by 6 kHz. The mean pressure reflectance phase angle (∠ECR) plotted on a linear frequency scale showed a group delay of approximately 0.1 ms for 0.2 – 6 kHz. Small significant differences were observed in |ECR|2 at the lowest frequencies between right and left ears, and between males and females at 4 kHz. |ECR|2 decreased with age, but reached significance only at 1 kHz. Our ECR measurements were generally similar to previous published reports. Highly significant negative correlations were found between |ECR|2 and VU for frequencies below 1 kHz. Significant correlations were also found between the tympanometrically determined peak total compliance and |ECR|2 and The results suggest that middle-ear compliance VU at frequencies below 1 kHz. contributes significantly to the measured power reflectance and umbo velocity at frequencies below 1 kHz, but not at higher frequencies.
This study has established a database of objective measurements of middle ear function (ear-canal reflectance, umbo velocity, tympanometry) in a population of strictly defined normal hearing ears. The data will promote our understanding of normal middle ear function, and will serve as a control for comparison to similar measurements made in pathological ears.
The goal of the present study was to investigate the clinical utility of measurements of ear-canal reflectance (ECR) in a population of patients with conductive hearing loss in the presence of an intact, healthy tympanic membrane (TM) and an aerated middle ear. We also sought to compare the diagnostic accuracy of umbo velocity (VU) measurements and measurements of ECR in the same group of patients.
This prospective study comprised 31 adult patients with conductive hearing loss, of which 14 had surgically-confirmed stapes fixation due to otosclerosis, 6 had surgically-confirmed ossicular discontinuity, and 11 had CT- and VEMP-confirmed superior semicircular canal dehiscence (SCD). Measurements on all 31 ears included pure-tone audiometry for 0.25 – 8 kHz, ECR for 0.2 – 6 kHz using the Mimosa Acoustics HearID system, and VU for 0.3 – 6 kHz using the HLV-1000 laser Doppler vibrometer (Polytec Inc). We analyzed power reflectance |ECR|2 as well as the absorbance level = 10×log10(1−|ECR|2). All measurements were made prior to any surgical intervention. The VU and ECR data were plotted against normative data obtained in a companion study of 58 strictly defined normal ears (Rosowski et al. 2011).
Small increases in |ECR|2 at low-to-mid frequencies (400–1000 Hz) were observed in cases with stapes fixation, while narrow-band decreases were seen for both SCD and ossicular discontinuity. The SCD and ossicular discontinuity differed in that the SCD had smaller decreases at mid-frequency (~1000 Hz), while ossicular discontinuity had larger decreases at lower frequencies (500–800 Hz). SCD tended to have less air-bone gap at high frequencies (1–4 kHz) compared to stapes fixation and ossicular discontinuity. The |ECR|2 measurements, in conjunction with audiometry, could successfully separate 28 of the 31 cases into the three pathologies. By comparison, VU measurements, in conjunction with audiometry, could successfully separate various pathologies in 29 of 31 cases.
The combination of |ECR|2 with audiometry showed clinical utility in the differential diagnosis of conductive hearing loss in the presence of an intact TM and an aerated middle ear, and appears to be of similar sensitivity and specificity to measurements of VU plus audiometry. Additional research is needed to expand upon these promising preliminary results.
While corticosteroid use in Acute Hemorrhagic Stroke (AHS) is not widely adopted, management with intravenous dexamethasone (IVDxM) has been standard of care at the University Hospital of Heraklion, Crete (UH-Crete) with observed outcomes superior to those reported in literature. To explore this further, we conducted a retrospective, multivariable-adjusted two-center study.
We studied 391 AHS cases admitted to UH-Crete between 1/1997 and 7/2010 and compared them with 510 AHS cases admitted to Massachusetts General Hospital, Boston from 1/2003 to 9/2009. Of the Cretan cases, 340 received a tapering scheme of IVDxM, starting with 16–32 mg/day, while the Boston patients were managed without steroids.
The two cohorts had comparable demographics and stroke severity on admission, although anticoagulation was more frequent in Boston. The in-hospital mortality was significantly lower on Crete (23.8%, n=340) than in Boston (38.0 %, n=510; p<0.001) as was the 30-day mortality (Crete: 25.4%, n=307; Boston: 39.4%, n=510; p<0.001). Exclusion of patients on anticoagulants showed even greater differences (30-day mortality: Crete 20.8%; n=259; Boston 37.0%; n=359; p<0.001). The improved survival on Crete was observed three days after initiation of IVDxM and was pronounced for deep-seated hemorrhages. After adjusting for AHS volume/location, GCS, hypertension, diabetes mellitus, smoking, coronary artery disease and statin, antiplatelet and anticoagulant use, IVDxM treatment was associated with better functional outcomes and significantly lower risk of death at 30-days (odds ratio 0.357; 95% C.I. 0.174–0.732).
This study suggests that IVDxM improves outcome in AHS and supports a randomized clinical trial using this approach.
ICH; Dexamethasone; stroke management
Fisheries bycatch is a recognized threat to marine megafauna. Addressing bycatch of pelagic species however is challenging owing to the dynamic nature of marine environments and vagility of these organisms. In order to assess the potential for species to overlap with fisheries, we propose applying dynamic habitat models to determine relative probabilities of species occurrence for specific oceanographic conditions. We demonstrate this approach by modelling habitats for Laysan (Phoebastria immutabilis) and black-footed albatrosses (Phoebastria nigripes) using telemetry data and relating their occurrence probabilities to observations of Hawaii-based longline fisheries in 1997–2000. We found that modelled habitat preference probabilities of black-footed albatrosses were high within some areas of the fishing range of the Hawaiian fleet and such preferences were important in explaining bycatch occurrence. Conversely, modelled habitats of Laysan albatrosses overlapped little with Hawaii-based longline fisheries and did little to explain the bycatch of this species. Estimated patterns of albatross habitat overlap with the Hawaiian fleet corresponded to bycatch observations: black-footed albatrosses were more frequently caught in this fishery despite being 10 times less abundant than Laysan albatrosses. This case study demonstrates that dynamic habitat models based on telemetry data may help to project interactions with pelagic animals relative to environmental features and that such an approach can serve as a tool to guide conservation and management decisions.
bycatch; dynamic habitat; marine conservation; modelling; telemetry