Use of cumulative incidence of novel influenza A/H1N1 in foreign travelers to estimate lower bounds on cumulative incidence in Mexico

Background: An accurate estimate of the total number of cases and severity of illness of an emerging infectious disease is required both to define the burden of the epidemic and to determine the severity of disease. When a novel pathogen first appears, affected individuals with severe symptoms are more likely to be diagnosed. Accordingly, the total number of cases will be underestimated and disease severity overestimated. This problem is manifest in the current epidemic of novel influenza A/H1N1. Methods and Results: We used a simple approach to leverage measures of incident influenza A/H1N1 among a relatively small and well observed group of US, UK, Spanish and Canadian travelers who had visited Mexico to estimate the incidence among a much larger and less well surveyed population of Mexican residents. We estimate that a minimum of 113,000 to 375,000 cases of novel influenza A/H1N1 have occurred in Mexicans during the month of April, 2009. Such an estimate serves as a lower bound because it does not account for underreporting of cases in travelers or for nonrandom mixing between Mexican residents and visitors, which together could increase the estimates by more than an order of magnitude. Conclusions: We find that the number of cases in Mexican residents may exceed the number of confirmed cases by two to three orders of magnitude. While the extent of disease spread is greater than previously appreciated, our estimate suggests that severe disease is uncommon since the total number of cases is likely to be much larger than those of confirmed cases

Growth and retreat of the last British–Irish Ice Sheet, 31 000 to 15 000 years ago: the BRITICE-CHRONO reconstruction

The BRITICE-CHRONO consortium of researchers undertook a dating programme to constrain the timing of advance, maximum extent and retreat of the British–Irish Ice Sheet between 31 000 and 15 000 years before present. The dating campaign across Ireland and Britain and their continental shelves, and across the North Sea included 1500 days of field investigation yielding 18 000 km of marine geophysical data, 377 cores of sea floor sediments, and geomorphological and stratigraphical information at 121 sites on land; generating 690 new geochronometric ages. These findings are reported in 28 publications including synthesis into eight transect reconstructions. Here we build ice sheet-wide reconstructions consistent with these findings and using retreat patterns and dates for the inter-transect areas. Two reconstructions are presented, a wholly empirical version and a version that combines modelling with the new empirical evidence. Palaeoglaciological maps of ice extent, thickness, velocity, and flow geometry at thousand-year timesteps are presented. The maximum ice volume of 1.8 m sea level equivalent occurred at 23 ka. A larger extent than previously defined is found and widespread advance of ice to the continental shelf break is confirmed during the last glacial. Asynchrony occurred in the timing of maximum extent and onset of retreat, ranging from 30 to 22 ka. The tipping point of deglaciation at 22 ka was triggered by ice stream retreat and saddle collapses. Analysis of retreat rates leads us to accept our hypothesis that the marine-influenced sectors collapsed rapidly. First order controls on ice-sheet demise were glacio-isostatic loading triggering retreat of marine sectors, aided by glaciological instabilities and then climate warming finished off the smaller, terrestrial ice sheet. Overprinted on this signal were second order controls arising from variations in trough topographies and with sector-scale ice geometric readjustments arising from dispositions in the geography of the landscape. These second order controls produced a stepped deglaciation. The retreat of the British–Irish Ice Sheet is now the world’s most well-constrained and a valuable data-rich environment for improving ice-sheet modelling.publishedVersio

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Connected speech in transient aphasias after left hemisphere resective surgery

BackgroundTransient aphasias are common in the first few days after resective surgery to the language-dominant hemisphere. The specific speech and language deficits that occur are related to the location of the surgical site, and may include impairments in fluency, lexical access, repetition, and comprehension. The impact of these transient aphasias on connected speech production has not previously been investigated.AimsThe goals of this study were to characterize the nature of connected speech deficits in the immediate post-surgical period, and to determine which deficits resolve completely within 1 month.Methods & proceduresForty-three patients undergoing resective surgery in the left (language-dominant) hemisphere participated in the study. Brief connected speech samples were obtained before surgery, and at 2-3 days post-surgery. In a subset of 24 patients (all of whom presented with aphasia in the immediate post-surgical period), follow-up samples were also obtained at 1 month post-surgery. The samples were transcribed and coded in CHAT format. Ten connected speech measures were derived from each speech sample, and were then compared by time point.Outcomes & resultsAt 2-3 days post surgery, deficits were observed in all 10 connected speech measures in comparison to pre-surgical samples: there were decreases in words per minute, words per utterance, and the use of embedded clauses, and increases in phonological errors, lexical access difficulties, morphosyntactic errors, filled pauses, false starts and retraced sequences. The proportion of closed class words could be perturbed in either direction. At 1 month post-surgery, 8 of the 10 connected speech measures had significantly improved, and all measures reflecting structural features (words per utterance, number of embeddings, morphosyntactic errors, proportion of words that were closed class) were equivalent to the pre-surgical time point. Subtle deficits persisted in some other measures; in particular, there were more phonological errors and lexical access difficulties than at the pre-surgical point.ConclusionsTransient aphasias after left hemisphere surgery impacted all aspects of connected speech in the immediate post-surgical period. Most of these deficits were largely or completely resolved by 1 month post surgery, but some subtle impairments persisted

Long-term Peripheral Neuropathy in Breast Cancer Patients Treated With Adjuvant Chemotherapy: NRG Oncology/NSABP B-30.

The long-term effects of chemotherapy are sparsely reported. Peripheral neuropathy (PN) is one of the most frequent toxicities associated with taxane use for the treatment of early-stage breast cancer. We investigated the impact of the three different docetaxel-based regimens and patient characteristics on long-term, patient-reported outcomes of PN and the impact of PN on long-term quality of life (QOL). The National Surgical Adjuvant Breast and Bowel Project Protocol B-30 was a randomized trial comparing sequential doxorubicin (A) and cyclophosphamide (C) followed by docetaxel (T) (AC→T), concurrent ACT, or AT in women with node-positive, early-stage breast cancer. The AC→T group had a higher cumulative dose of T. PN was one of the symptoms assessed in a QOL substudy. Statistical methods included simple and mixed ordinal logistic regression and general linear models. All statistical tests were two-sided. Of 1512 patients, 41.9% reported PN two years after treatment initiation. Treatment with AT and ACT was associated with less severe long-term PN compared with AC→T (odds ratio [OR] = 0.45, 95% confidence interval [CI] = 0.35 to 0.58; OR = 0.59, 95% CI = 0.46 to 0.75). Preexisting PN, older age, obesity, mastectomy, and greater number of positive nodes were also associated with higher risk of long-term PN. Patients who reported worse PN symptoms at 24 months had statistically significantly worse QOL (Ptrend < .001). The administration of docetaxel is associated with long-term PN. The lower rate of long-term PN in AT and ACT patients might be an important consideration in supporting choosing these therapies for individuals with preexisting neuropathic symptoms or other risk factors for neuropathy

Cases of novel influenza A/H1N1 among travelers to Mexico from three countries as of May 6, 2009 (Canada) or May 8, 2009 (US, UK, Spain) and associated estimates.

<p>Cases of novel influenza A/H1N1 among travelers to Mexico from three countries as of May 6, 2009 (Canada) or May 8, 2009 (US, UK, Spain) and associated estimates.</p

Maximum extent and readvance dynamics of the Irish Sea Ice Stream since the Last Glacial Maximum

International audienceThe Irish Sea Ice Stream (ISIS) has long had one of the best documented retreat histories of the British-Irish Ice Sheet (BIIS) and was the first ice stream to be constrained by Bayesian analysis of geochronological data. These attributes made it a model system for the BRITICE-CHRONO research project, which aims to produce the best constrained retreat record of any palaeo-ice sheet contributing key observational constraints for ice sheet modelling. The project has generated a suite of new radiocarbon ages from deglacial sequences offshore in the Celtic and Irish seas and terrestrial cosmogenic nuclide and optically-stimulated luminescence ages from ice-marginal sites in the Isles of Scilly, Ireland, Wales and NW England. The ISIS was unusual within the former BIIS, in that it was a compound ice stream with two outlets, one marine terminating that flowed through the Irish Sea Basin into the Celtic Sea, and a terrestrial terminus that flowed southwards through Cheshire-Shropshire lowlands into the English Midlands around 25.5 ka. Here we assess the retreat dynamics across the entirety of the ISIS, integrating the new chronology in a revised Bayesian analysis that constrains the pattern and timing ice marginal fluctuations. The retreat chronology in the Irish Sea is better constrained than in the Celtic Sea, where the ISIS is now recognised to have extended as far as the continental shelf break to the SW of Britain and Ireland between 24 and 27 ka; this advance was synchronous with independently-dated ice-rafted detritus from ISIS in adjacent deep-sea cores. The ISIS then retreated rapidly northwards through the Celtic Sea, with evidence for readvance phases, deglaciating the Isles of Scilly at 25.5 ka, reaching St Georges Channel by 24.3 ka and the Llŷn Peninsula by 23.9 ka. The initiation of retreat from both the eastern (terrestrial) and western (marine) components of ISIS was synchronous. The eastern terrestrial lobe had vacated the Cheshire-Shropshire lowlands by 22-21 ka. The complex readvance sequences identified on the Llŷn (24-20ka) and in eastern Ireland have now been tightly constrained to register centennial-scale oscillations of the ice front driven by internal ice dynamics over topographic pinning points and constrictions of the ice-stream. Retreat northwards into the northern Irish Sea then accelerated, first evacuating the deeper water of the western Irish Sea, and developing pronounced ice margins across the northern Isle of Man by 19.1 ka. The final retreat phase, with ice margins pulling back onto terrestrial settings in the English Lake District, the north of Ireland and SW Scotland around 17 ka, was a deglaciation accomplished in a fully marine context evidenced by the preservation on the seabed of subglacial landforms and by increasing influence of local ice sources with flow realignment during draw-down and ice margin retreat