The Geographic Synchrony of Seasonal Influenza: A Waves across Canada and the United States

BACKGROUND: As observed during the 2009 pandemic, a novel influenza virus can spread globally before the epidemic peaks locally. As consistencies in the relative timing and direction of spread could form the basis for an early alert system, the objectives of this study were to use the case-based reporting system for laboratory confirmed influenza from the Canadian FluWatch surveillance program to identify the geographic scale at which spatial synchrony exists and then to describe the geographic patterns of influenza A virus across Canada and in relationship to activity in the United States (US). METHODOLOGY/PRINCIPAL FINDINGS: Weekly laboratory confirmations for influenza A were obtained from the Canadian FluWatch and the US FluView surveillance programs from 1997/98 to 2006/07. For the six seasons where at least 80% of the specimens were antigenically similar, we identified the epidemic midpoint of the local/regional/provincial epidemics and analyzed trends in the direction of spread. In three out of the six seasons, the epidemic appeared first in Canada. Regional epidemics were more closely synchronized across the US (3-5 weeks) compared to Canada (5-13 weeks), with a slight gradient in timing from the southwest regions in the US to northeast regions of Canada and the US. Cities, as well as rural areas within provinces, usually peaked within a couple of weeks of each other. The anticipated delay in peak activity between large cities and rural areas was not observed. In some mixed influenza A seasons, lack of synchronization sub-provincially was evident. CONCLUSIONS/SIGNIFICANCE: As mixing between regions appears to be too weak to force a consistency in the direction and timing of spread, local laboratory-based surveillance is needed to accurately assess the level of influenza activity in the community. In comparison, mixing between urban communities and adjacent rural areas, and between some communities, may be sufficient to force synchronization

Estimating Sensitivity of Laboratory Testing for Influenza in Canada through Modelling

Background: The weekly proportion of laboratory tests that are positive for influenza is used in public health surveillance systems to identify periods of influenza activity. We aimed to estimate the sensitivity of influenza testing in Canada based on results of a national respiratory virus surveillance system. Methods and Findings: The weekly number of influenza-negative tests from 1999 to 2006 was modelled as a function of laboratory-confirmed positive tests for influenza, respiratory syncytial virus (RSV), adenovirus and parainfluenza viruses, seasonality, and trend using Poisson regression. Sensitivity was calculated as the number of influenza positive tests divided by the number of influenza positive tests plus the model-estimated number of false negative tests. The sensitivity of influenza testing was estimated to be 33 % (95%CI 32–34%), varying from 30–40 % depending on the season and region. Conclusions: The estimated sensitivity of influenza tests reported to this national laboratory surveillance system is considerably less than reported test characteristics for most laboratory tests. A number of factors may explain this difference, including sample quality and specimen procurement issues as well as test characteristics. Improved diagnosis would permit better estimation of the burden of influenza

Comparison of the Antiseptic Efficacy of Tissue-Tolerable Plasma and an Octenidine Hydrochloride-Based Wound Antiseptic on Human Skin

Colonization and infection of wounds represent a major reason for the impairment of tissue repair. Recently, it has been reported that tissue-tolerable plasma (TTP) is highly efficient in the reduction of the bacterial load of the skin. In the present study, the antiseptic efficacy of TTP was compared to that of octenidine hydrochloride with 2-phenoxyethanol. Both antiseptic methods proved to be highly efficient. Cutaneous treatment of the skin with octenidine hydrochloride and 2-phenoxyethanol leads to a 99% elimination of the bacteria, and 74% elimination is achieved by TTP treatment. Technical challenges with an early prototype TTP device could be held responsible for the slightly reduced antiseptic properties of TTP, compared to a standard antiseptic solution, since the manual treatment of the skin surface with a small beam of the TTP device might have led to an incomplete coverage of the treated area

Characterization of a ballistic supermirror neutron guide

We describe the beam characteristics of the first ballistic supermirror neutron guide H113 that feeds the neutron user facility for particle physics PF1B of the Institute Laue-Langevin, Grenoble (ILL). At present, the neutron capture flux density of H113 at its 20x6cm2 exit window is 1.35x10^10/cm^2/s, and will soon be raised to above 2x10^10/cm^2/s. Beam divergence is no larger than beam divergence from a conventional Ni coated guide. A model is developed that permits rapid calculation of beam profiles and absolute event rates from such a beam. We propose a procedure that permits inter-comparability of the main features of beams emitted from ballistic or conventional neutron guides.Comment: 15 pages, 11 figures, to be submitted to Nuclear Instruments and Methods

Routine use of completion imaging after infrainguinal bypass is not associated with higher bypass graft patency

BackgroundSignificant variability exists in completion imaging (CIM) after infrainguinal lower extremity bypass (LEB). We evaluated the use of CIM and compared graft patency in patients treated by surgeons who performed routine CIM vs those who performed selective CIM.MethodsWe reviewed the Vascular Study Group of New England database (2003-2010) and assessed the use of CIM (angiography or duplex ultrasound) among patients undergoing LEB. The surgeon-specific CIM strategy was categorized as routine (≥80% of LEBs) vs selective (<80% of LEBs). Exclusion criteria included acute limb ischemia, bilateral procedures, and surgeon volume <10 cases per study period. Primary graft patency at discharge and at 1 year was analyzed on the basis of CIM use and surgeon-specific CIM strategy. Multivariable analyses were performed using Poisson regression.ResultsAmong 2032 LEB procedures performed by 48 surgeons, CIM was used in 1368 cases (67.3%). CIM was performed in 72% of autogenous LEBs and 52% of prosthetic grafts. Dialysis (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.1-2.6; P = .01), elective LEB (OR, 2.6; 95% CI, 1.4-4.8; P = .002), great saphenous vein conduit (OR, 2.0; 95% CI, 1.6-2.5; P < .001), and tibial or pedal target artery (OR, 1.8; 95% CI, 1.4-2.3; P < .001) were associated with CIM use. In multivariate models, CIM was not associated with improved primary graft patency at discharge (OR, 1.1; 95% CI, 0.7-1.7; P = .64) or at 1 year (OR, 0.9; 95% CI, 0.7-1.2; P = .47). Sixteen surgeons (33%) were routine users and 32 (67%) were selective users of CIM. Among patients of routine vs selective CIM users, primary graft patency at discharge and at 1 year was 96% vs 94% (P = .21) and 68% vs 72% (P = .09), respectively. In multivariate analysis, routine or selective CIM strategy was not associated with improved discharge (rate ratio, 0.8; 95% CI, 0.6-1.1; P = .31) or 1-year (rate ratio, 1.1; 95% CI, 0.9-1.2; P = .56) graft patency.ConclusionsIn our observational cohort, CIM does not improve short-term and 1-year bypass graft patency in infrainguinal LEB. The surgeon-specific strategy of selective CIM after LEB has outcomes comparable to those of routine CIM

Critical Limb Ischemia

Critical limb ischemia (CLI), defined as chronic ischemic rest pain, ulcers, or gangrene attributable to objectively proven arterial occlusive disease, is the most advanced form of peripheral arterial disease. Traditionally, open surgical bypass was the only effective treatment strategy for limb revascularization in this patient population. However, during the past decade, the introduction and evolution of endovascular procedures have significantly increased treatment options. In a certain subset of patients for whom either surgical or endovascular revascularization may not be appropriate, primary amputation remains a third treatment option. Definitive high-level evidence on which to base treatment decisions, with an emphasis on clinical and cost effectiveness, is still lacking. Treatment decisions in CLI are individualized, based on life expectancy, functional status, anatomy of the arterial occlusive disease, and surgical risk. For patients with aortoiliac disease, endovascular therapy has become first-line therapy for all but the most severe patterns of occlusion, and aortofemoral bypass surgery is a highly effective and durable treatment for the latter group. For infrainguinal disease, the available data suggest that surgical bypass with vein is the preferred therapy for CLI patients likely to survive 2 years or more, and for those with long segment occlusions or severe infrapopliteal disease who have an acceptable surgical risk. Endovascular therapy may be preferred in patients with reduced life expectancy, those who lack usable vein for bypass or who are at elevated risk for operation, and those with less severe arterial occlusions. Patients with unreconstructable disease, extensive necrosis involving weight-bearing areas, nonambulatory status, or other severe comorbidities may be considered for primary amputation or palliative measures

Immediate reexploration for the perioperative neurologic event after carotid endarterectomy: Is it worthwhile?

AbstractPurpose: When managing a new neurologic deficit after carotid endarterectomy (CEA), the surgeon is often preoccupied with determining the cause of the problem, requesting diagnostics tests, and deciding whether the patient should be surgically reexplored. The goal of this study was to analyze a series of perioperative neurologic events and to determine if careful analysis of their timing and mechanisms can predict which cases are likely to improve with reoperation. Methods: A review of 2024 CEAs performed from 1985 to 1997 revealed 38 patients who manifested a neurologic deficit in the perioperative period (1.9%). These cases form the focus of this analysis. Results: The causes of the events included intraoperative clamping ischemia in 5 patients (13.2%); thromboembolic events in 24 (63.2%); intracerebral hemorrhage in 5 (13.2%); and deficits unrelated to the operated artery in 4 (10.5%). Neurologic events manifesting in the first 24 hours after surgery were significantly more likely to be caused by thromboembolic events than by other causes of stroke (88.0% vs 12.0%, P <.002); deficits manifesting after the first 24 hours were significantly more likely to be related to other causes. Of 25 deficits manifesting in the first 24 hours after surgery, 18 underwent immediate surgical reexploration. Intraluminal thrombus was noted in 15 of the 18 reexplorations (83.3%); any technical defects were corrected. After the 18 reexplorations, in 12 cases there was either complete resolution of or significant improvement in the neurologic deficit that had been present (66.7%). Conclusions: Careful analysis of the timing and presentation of perioperative neurologic events after CEA can predict which cases are likely to improve with reoperation. Neurologic deficits that present during the first 24 hours after CEA are likely to be related to intraluminal thrombus formation and embolization. Unless another etiology for stroke has clearly been established, we think immediate reexploration of the artery without other confirmatory tests is mandatory to remove the embolic source and correct any technical problems. This will likely improve the neurologic outcome in these patients, because an uncorrected situation would lead to continued embolization and compromise. (J Vasc Surg 2000;32:1062-70.

Promoter keyholes enable specific and persistent multi-gene expression programs in primary T cells without genome modification

Non-invasive epigenome editing is a promising strategy for engineering gene expression programs, yet potency, specificity, and persistence remain challenging. Here we show that effective epigenome editing is gated at single-base precision via 'keyhole' sites in endogenous regulatory DNA. Synthetic repressors targeting promoter keyholes can ablate gene expression in up to 99% of primary cells with single-gene specificity and can seamlessly repress multiple genes in combination. Transient exposure of primary T cells to keyhole repressors confers mitotically heritable silencing that persists to the limit of primary cultures in vitro and for at least 4 weeks in vivo, enabling manufacturing of cell products with enhanced therapeutic efficacy. DNA recognition and effector domains can be encoded as separate proteins that reassemble at keyhole sites and function with the same efficiency as single chain effectors, enabling gated control and rapid screening for novel functional domains that modulate endogenous gene expression patterns. Our results provide a powerful and exponentially flexible system for programming gene expression and therapeutic cell products