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In a series of three experiments, we explored the nature of implicit representations in change blindness (CB). Using 3 x 3 letter arrays, we asked subjects (Ss) to locate changes in paired arrays separated by 80 ms ISIs, in which one, two or three letters of a row in the second array changed. In one testing version, a tone followed the second array, signaling a row for partial report (PR). In the other version, no PR was required. After Ss reported whether a change had been detected and the PR had been completed (if required), they were asked to identify a degraded letter trigram that was either novel, or from a previously shown row (repetition priming). Our findings indicate that when CB occurs, both the pre-change and post-change stimulus information primes despite its unavailability to consciousness. Surprisingly, findings also indicate that when change detection occurs only the post-change information primes.

The apparent diffusion coefficient of hyperpolarized (3)He in the lungs has been shown to correlate directly in animal models with the peripheral airspace size and can detect changes in lung microstructure.To study in vivo the (3)He apparent diffusion coefficient and to demonstrate its sensitivity to changes in lung morphometry as a result of aging, exposure to cigarette smoke, and lung inflation.We assessed the variation in the diffusion of hyperpolarized (3)He gas in the lungs by magnetic resonance techniques. Spirometric lung volumes were recorded.We measured the dependence of (3)He diffusion on age and on reported cigarette smoke exposure in 32 symptom-free adults. We also measured the dependence of the apparent diffusion coefficient on the degree of lung inflation.In healthy never-smokers, the apparent diffusion coefficient increased with age from 0.115 to 0.155 cm(2) . s(-1) at 20 and 70 yr, respectively, increased linearly with lung inflation and was independent of individual's lung size after correcting for age. For active and passive smokers, the apparent diffusion coefficient increased by up to 40% compared with never-smokers with mean values significantly higher (p=0.016 and p=0.0007, respectively).Peripheral airspace size increases with age and after exposure to smoke in healthy adults in agreement with previous histologic studies. We have confirmed in vivo that peripheral airspace size is independent of intersubject lung size.

Background Concerns about the safety of pediatric oral sedation and the incremental use of triazolam in adults prompted a workshop cosponsored by several professional organizations. Overview There is a strong need and demand for adult and pediatric sedation services. Using oral medication to achieve anxiolysis in adults appears to have a wide margin of safety. Mortality and serious morbidity, however, have been reported with oral conscious sedation, especially in young children. Most serious adverse events are related to potentially avoidable respiratory complications. Conclusions Clinical trials are needed to evaluate oral sedative drugs and combinations, as well as to develop discharge criteria with objective quantifiable measures of home readiness. Courses devoted to airway management should be developed for dentists who provide conscious sedation services. State regulation of enteral administration of sedatives to achieve conscious sedation is needed to ensure safety. Practice Implications Safety in outpatient sedation is of paramount concern, with enteral administration of benzodiazepines appearing safe but poorly documented in the office setting. Conscious sedation by the enteral route, including incremental triazolam, necessitates careful patient evaluation, monitoring, documentation, facilities, equipment and personnel as described in American Dental Association and American Academy of Pediatric Dentistry guidelines.

Background: Particulate matter 10 ) from fossil fuel combustion is associated with an increased prevalence of respiratory symptoms in children and adolescents. However, the effect of PM 10 on respiratory symptoms in young children is unclear. Methods: The association between primary PM 10 (particles directly emitted from local sources) and the prevalence and incidence of respiratory symptoms was studied in a random sample cohort of 4400 Leicestershire children aged 1–5 years surveyed in 1998 and again in 2001. Annual exposure to primary PM 10 was calculated for the home address using the Airviro dispersion model and adjusted odds ratios (ORS) and 95% confidence intervals were calculated for each μg/m 3 increase. Results: Exposure to primary PM 10 was associated with the prevalence of cough without a cold in both 1998 and 2001, with adjusted ORs of 1.21 (1.07 to 1.38) and 1.56 (1.32 to 1.84) respectively. For night time cough the ORs were 1.06 (0.94 to 1.19) and 1.25 (1.06 to 1.47), and for current wheeze 0.99 (0.88 to 1.12) and 1.28 (1.04 to 1.58), respectively. There was also an association between primary PM 10 and new onset symptoms. The ORs for incident symptoms were 1.62 (1.31 to 2.00) for cough without a cold and 1.42 (1.02 to 1.97) for wheeze. Conclusion: In young children there was a consistent association between locally generated primary PM 10 and the prevalence and incidence of cough without a cold and the incidence of wheeze which was independent of potential confounders.

The current study aimed to assess prevalence and distribution of use of asthma medication for wheeze in pre-school children in the community. We sent a postal questionnaire to the parents of a random population-based sample of 4,277 UK children aged 1-5 years; 3,410 participated (children of south Asian decent were deliberately over-represented). During the previous 12 months, 18% of the children were reported to have received bronchodilators, 8% inhaled corticosteroids (ICS) and 3% oral corticosteroids. Among current wheezers these proportions were 55%, 25%, and 12%, respectively. Use of ICS increased with reported severity of wheeze, but did not reach 60% even in the most severe category. In contrast, 42% of children receiving ICS reported no or very infrequent recent wheeze. Among children with the episodic viral wheeze phenotype, 17% received ICS compared with 40% among multiple-trigger wheezers. Use of ICS by current wheezers was less common in children of South Asian ethnicity and in girls. Although a high proportion of pre-school children in the community used asthma inhalers, treatment seemed to be insufficiently adjusted to severity or phenotype of wheeze, with relative under-treatment of severe wheeze with ICS, especially in girls and South Asian children, but apparent over-treatment of mild and episodic viral wheeze and chronic cough.

Background Budesonide is the only inhaled corticosteroid to be given a category B pregnancy rating by the US Food and Drug Administration, based on observational data from the Swedish Medical Birth Registry. However, data from large randomized controlled trials are lacking. Objective To compare pregnancy outcomes among patients with recent-onset mild-to-moderate persistent asthma receiving low-dose budesonide vs placebo. Methods In a randomized, double-blind, placebo-controlled trial, 7,241 patients aged 5 to 66 years with mild-to-moderate persistent asthma for less than 2 years and no previous regular corticosteroid therapy received once-daily budesonide or placebo via dry powder inhaler in addition to their usual asthma medication for 3 years. This trial was followed by a 2-year open-label treatment period. The daily dose of budesonide was 400 μg for adults. The study included 2,473 females aged 15 to 50 years at randomization. Pregnancy was not an exclusion criterion (except for US patients). Results Of 319 pregnancies reported, 313 were analyzed. Healthy children were delivered in 81% and 77% of all pregnancies in the budesonide and placebo groups, respectively. Of the 196 pregnancies reported by participants taking budesonide, 38 (19%) had adverse outcomes: 23 (12%) had miscarriages, 3 (2%) had congenital malformations, and 12 (6%) had other outcomes. Of the 117 pregnancies reported in the placebo group, 27 (23%) had adverse outcomes: 11 (9%) had miscarriages, 4 (3%) had congenital malformations, and 12 (10%) had other outcomes. Conclusions Treatment with low-dose inhaled budesonide in females with mild-to-moderate persistent asthma does not seem to affect the outcome of pregnancy.

Asthma is an increasing health problem worldwide, but the long-term temporal pattern of clinical symptoms is not understood and predicting asthma episodes is not generally possible. We analyse the time series of peak expiratory flows, a standard measurement of airway function that has been assessed twice daily in a large asthmatic population during a long-term crossover clinical trial. Here we introduce an approach to predict the risk of worsening airflow obstruction by calculating the conditional probability that, given the current airway condition, a severe obstruction will occur within 30 days. We find that, compared with a placebo, a regular long-acting bronchodilator (salmeterol) that is widely used to improve asthma control decreases the risk of airway obstruction. Unexpectedly, however, a regular short-acting beta2-agonist bronchodilator (albuterol) increases this risk. Furthermore, we find that the time series of peak expiratory flows show long-range correlations that change significantly with disease severity, approaching a random process with increased variability in the most severe cases. Using a nonlinear stochastic model, we show that both the increased variability and the loss of correlations augment the risk of unstable airway function. The characterization of fluctuations in airway function provides a quantitative basis for objective risk prediction of asthma episodes and for evaluating the effectiveness of therapy.

Background : Studies into the effects of salbutamol in the treatment of wheeze in infancy have been conflicting, possibly due to differences in outcome variables. We aimed to assess the response to salbutamol using indices derived from passive and forced expiration. Methods : We recruited 39 infants who had a history of wheezing (mean age 43 weeks) and measured maximum flow at functional residual capacity (V′maxFRC) by rapid thoracoabdominal compression (RTC), and forced expired volume at 0.4s (FEV 0.4 ) using the raised-volume RTC technique (RV-RTC). We calculated passive compliance ( C rs ), resistance ( R rs ) and time constant ( τ ) from relaxed expirations that followed the augmented inspirations delivered during RV-RTC. Measurements were repeated after aerosol salbutamol (800mcg). Results : Data were obtained in 32 infants for V′maxFRC, 22 for FEV 0.4 and 19 for passive mechanics. There were no mean changes in any index of forced expiration after salbutamol. Some individuals showed significant changes (improvement or worsening) in one or other index. Overall, there was a small increase in C rs after salbutamol but no change in R rs or τ . Conclusions : We found no consistent pattern of response in either index of forced expiration. Validated clinical scores or alternative physiological techniques may be preferable to respiratory mechanics in assessing bronchodilator response.

Background This study examines the following questions: In moderately disabled readers, will temporal vision-processing therapy procedures that benefit reading comprehension, visual attention, and oculomotor skills ameliorate M-cell processing deficits as measured with coherent motion threshold testing ? And will the results show a corresponding improvement in oral reading and verbal skills? Method A sample of 16 moderately disabled readers, evaluated in a study completed 6 months earlier, were retested with another form of the Gates–MacGinitie Reading Test. Each participant was additionally tested for coherent motion, oral reading, and word attack skills. During the succeeding 6 months, fifteen 45-minute therapy sessions were administered once a week (as the school schedule permitted). After completing 15 therapy sessions, the initial testing procedures were repeated. Results All four variables—namely, Gates–MacGinitie Reading Test, Coherent Motion Threshold Test, Gray Oral Reading Test, and Woodcock-Johnson Word Attack Test— revealed significant improvements after temporal vision therapy. Half of the 16 participants improved 2 or more years in reading comprehension, compared to no significant mean difference following the 6-month “control period” before the onset of therapy. Conclusions This research supports the value of rendering temporal vision therapy to children identified as moderately reading disabled (RD). The diagnostic procedures and the dynamic therapeutic techniques discussed in this article have not been previously used for the specific purpose of ameliorating an M-cell deficit. Improved temporal visual-processing skills and enhanced visual motion discrimination appear to have a salutary effect on magnocellular processing and reading comprehension in RD children with M-cell deficits.

We measured arterial diameter as a function of generation number (#) in the arteriograms of six postmortem lung preparations from human infants aged 35 to 48 wks post-conceptional age (PCA). The log-log plot of mean diameter as a function of generation number revealed a linear decrease in mean and median diameter with increasing #, which was characterized by its slope alpha and intercept beta (linear regression). The mean arterial diameter per generation as well as the ratio (F) between mother and larger daughter branch and the relative ratio of asymmetry (A) between the larger and the smaller daughter branch was calculated. The values of F(#) and A(#) were found to be constant between 2 and 15 generations in individual lungs which is consistent with the pulmonary arterial tree exhibiting fractal properties. The averaged values (F and A within a subject) of F(#) and A(#) as well as alpha and beta were determined for each lung preparation and found to be constant from 35 to 48 weeks of age, revealing unchanged branching properties in the pre- and postnatal phase of human lung development.

This study quantified the influence of visual attention therapy on the reading comprehension of Grade 6 children with moderate reading disabilities (RD) in the absence of specific reading remediation. Thirty students with below-average reading scores were identified using standardized reading comprehension tests. Fifteen children were placed randomly in the experimental group and 15 in the control group. The Attention Battery of the Cognitive Assessment System was administered to all participants. The experimental group received 12 one-hour sessions of individually monitored, computer-based attention therapy programs; the control group received no therapy during their 12-week period. Each group was retested on attention and reading comprehension measures. In order to stimulate selective and sustained visual attention, the vision therapy stressed various aspects of arousal, activation, and vigilance. At the completion of attention therapy, the mean standard attention and reading comprehension scores of the experimental group had improved significantly. The control group, however, showed no significant improvement in reading comprehension scores after 12 weeks. Although uncertainties still exist, this investigation supports the notion that visual attention is malleable and that attention therapy has a significant effect on reading comprehension in this often neglected population.

Summary Background We have previously reported an experimental infection of young adults with a history of episodic and exclusive viral wheeze (EVW) using human coronavirus, in which 16 of 24 with EVW (15 atopic) and 11 of 19 healthy controls (seven atopic) developed a symptomatic cold with evidence of infection, but only those with EVW developed lower respiratory tract symptoms and increased airway responsiveness. Objective The aim of this study was to compare the EVW and control groups from this study for inflammatory changes occurring in the upper and lower respiratory tracts during the experimental infection, in particular, to determine whether eosinophil-driven inflammation was associated with EVW. Methods Nasal lavage and induced sputum were collected prior to inoculation (day 0) and 2, 4 and 17 days later. Differential cell counts were performed and supernatant was assayed for IL-8, IL-5, IFN-γ, and eosinophilic cationic protein (ECP). Results There was no difference between the two groups in any measurement at baseline. In both groups, during colds the volume of nasal secretion increased as did leucocyte counts in both upper and lower respiratory tracts. A modest increase in nasal neutrophil count was seen in both EVW and control groups with symptomatic colds on day 2 (median (quartile) difference from baseline 5.4 (0.0, 11.0) and 1.8 (−1.1, 2.2)×104/mL of secretions, respectively). The change in nasal neutrophil counts in all subjects correlated with nasal symptom scores. A significant relative increase in sputum differential neutrophil count was seen on day 4 in the EVW group with a cold but not in controls (mean difference (95% confidence interval) 20.4 (9.6, 31.1)% and 3.1 (−8.2, 14.5)%, respectively, P

This article evaluates a motivational intervention based on the theory of planned behavior, a volitional intervention based on implementation intentions, and a combined motivational plus volitional intervention in promoting attendance at workplace health and safety training courses in the UK. Intervention manipulations were embedded in postal questionnaires completed by participants (N=271). Subsequent attendance over a 3-month period was determined from course records. Findings showed that the volitional and combined interventions doubled the rate of attendance compared to the motivational and control conditions (rates were 39%, 32%, 12%, and 16%, respectively). The effects of the volitional intervention were independent of the effects of previous attendance, demographic variables, employment characteristics, and variables from the theory of planned behavior.

Attention is necessary for the conscious perception of any object. Objects not attended to are not seen. What is it that captures attention when we are engaged in some attention-absorbing task? Earlier research has shown that there are only a very few stimuli which have this power and therefore are reliably detected under these conditions (for example, Mack & Rock, 1998; Moray, 1959). The two most reliable are the observer's own name and a happy face icon which seem to capture attention by virtue of their meaning. Three experiments are described which explore whether these stimuli are detected under conditions, heretofore unexamined, which either cause inattentional blindness or are associated with a perceptual failure associated with the limits of attention. The evidence obtained indicates that these stimuli have a unique capacity to capture and extend the limits of attention under conditions in which this has been deemed highly unlikely.

Reducing inappropriate antibiotic prescribing for acute upper respiratory tract infections (AURIs) requires a better understanding of the factors associated with this practice.To determine the prevalence of antibiotic prescribing for nonbacterial AURIs and whether prescribing rates varied by physician characteristics.Retrospective analysis of linked administrative health care data.Primary care physician practices in Ontario, Canada (January-December 2012).Patients aged 66 years or older with nonbacterial AURIs. Patients with cancer or immunosuppressive conditions and residents of long-term care homes were excluded.Antibiotic prescriptions for physician-diagnosed AURIs. A multivariable logistic regression model with generalized estimating equations was used to examine whether prescribing rates varied by physician characteristics, accounting for clustering of patients among physicians and adjusting for patient-level covariates.The cohort included 8990 primary care physicians and 185 014 patients who presented with a nonbacterial AURI, including the common cold (53.4%), acute bronchitis (31.3%), acute sinusitis (13.6%), or acute laryngitis (1.6%). Forty-six percent of patients received an antibiotic prescription; most prescriptions were for broad-spectrum agents (69.9% [95% CI, 69.6% to 70.2%]). Patients were more likely to receive prescriptions from mid- and late-career physicians than early-career physicians (rate difference, 5.1 percentage points [CI, 3.9 to 6.4 percentage points] and 4.6 percentage points [CI, 3.3 to 5.8 percentage points], respectively), from physicians trained outside of Canada or the United States (3.6 percentage points [CI, 2.5 to 4.6 percentage points]), and from physicians who saw 25 to 44 patients per day or 45 or more patients per day than those who saw fewer than 25 patients per day (3.1 percentage points [CI, 2.1 to 4.0 percentage points] and 4.1 percentage points [CI, 2.7 to 5.5 percentage points], respectively).Physician rationale for prescribing was unknown.In this low-risk elderly cohort, 46% of patients with a nonbacterial AURI were prescribed antibiotics. Patients were more likely to receive prescriptions from mid- or late-career physicians with high patient volumes and from physicians who were trained outside of Canada or the United States.Ontario Ministry of Health and Long-term Care, Academic Medical Organization of Southwestern Ontario, Schulich School of Medicine and Dentistry, Western University, and Lawson Health Research Institute.

Abstract 9 Background: In Uganda, cervical cancer is the leading cause of cancer death, affecting 45 in every 100,000 women annually and killing 25 in every 100,000 annually. To effect change, two Canadian registered charities partnered with a Ugandan nongovernmental organization, a university, and the Ministry of Health to develop a novel screening, treatment, and educational training program. The two major goals of our program were to develop a training program for health care providers in southwestern Uganda for visual inspection of the cervix with acetic acid (VIA) and a cryotherapy see and treat model; and to implement the first cervical cancer screening program of its kind in the Kabale region of southwestern Uganda. Methods: Our program was developed in partnership with Mbarara University of Science and Technology, a grass-roots Ugandan community development organization (Kigezi Healthcare Foundation [KIHEFO]), a Canadian charity that is focused on providing medical and dental care and educational training and infrastructure development (Bridge to Health Medical and Dental), and a Canadian charity that is focused on treatment for advanced cervical cancer (Road to Care). Results: Requisite supplies were obtained by Bridge to Health Medical and Dental and left behind with KIHEFO. A partnership was formed between academia, government, and civil society across Canada and Uganda. Over 5 days, 15 Ugandan health care workers were trained in VIA and cryotherapy, and 96 patients were screened for cervical cancer. Six patients were successfully treated for precancerous lesions. One biopsy was sent for pathology review and analysis. Conclusion: Since the pilot program, KIHEFO has conducted two additional cervical cancer screening programs using VIA and the see and treat approach. A new cervical cancer screening and treatment campaign, along with a quality control and educational training refresher, for the original 15 health care providers is planned for February 2017. Funding: Bridge to Health Medical and Dental and Kigezi Healthcare Foundation in partnership with the Ugandan Ministry of Health. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST No COIs from the authors.

A 45-year-old woman presented to a clinic in rural Uganda with a 1-year history of a progressively enlarging ulcerated mass on the hard palate. The mass had initially been painless but recently had become painful and was causing difficulty in speaking and swallowing.

Background. Protease inhibitor (PI)–based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that PIs contribute to these adverse events by altering progesterone levels. Methods. PI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women. Results. PIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving PI-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile. Conclusions. Our data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes.

This chapter focuses on the different molecular mechanisms two model luminous bacteria, Vibrio fischeri (a symbiont) and V. harveyi (a free-living microbe), use for regulating lux expression. Expression of luminescence in most bacteria is tightly regulated by the density of the population. In V. fischeri, the regulatory genes involved in density-dependent control of luminescence are adjacent to the luxCDABEG operon encoding the luciferase enzymes. The regulatory genes that control luminescence in V. harveyi are different from those of V. fischeri. One complementation group of V. harveyi dim mutants could be restored to full light production by a family of recombinant cosmids containing a subset of common restriction fragments. Initial HAI-1 and HAI-2 signal recognition by LuxN and LuxQ could activate a series of phosphotransfer reactions. Two-component circuits have been characterized in which a single protein contains both a sensor kinase and a response regulator domain (similar to LuxN and LuxQ) and a second protein contains both a response regulator domain and a DNA binding motif (similar to LuxO). The differences between the regulatory circuits controlling density-dependent expression of luminescence in V. fischeri and V. harveyi are striking. Subsequent mutations and gene duplications and rearrangements generated new and multiple autoinducers, receptivities, and regulatory connections, finally resulting in a bacterium with the properties of V. harveyi.

Background Zimbabwe underwent a socioeconomic crisis and resultant increase in food insecurity in 2008–9. The impact of the crisis on Tuberculosis (TB) incidence is unknown. Methods Prospective databases from two mission hospitals, which were geographically widely separated, and remained open during the crisis, were reviewed. Results At the Howard Hospital (HH) in northern Zimbabwe, TB incidence increased 35% in 2008 from baseline rates in 2003–2007 (p

Distinct wheezing disorders co-exist in young (preschool) children, some of which (early transient wheeze and viral wheeze) are thought to be unrelated to atopy. Investigation of changes in prevalence of wheezing disorders in preschool children could provide important clues about underlying mechanisms responsible for increasing prevalence of asthma in schoolchildren.Repeated population surveys of the prevalence of respiratory symptoms were done by parent-completed postal questionnaires in random samples of 1650 (1990) and 2600 (1998) caucasian children aged 1-5 years living in the county of Leicestershire, UK.The response rates were 86% (1422 of 1650) in 1990 and 84% (2127 of 2522) in 1998. Between 1990 and 1998, there was a significant increase in the prevalance of reported wheeze ever (16% to 29%, p0.0001), current wheeze (12% to 26%, p0.0001), diagnosis of asthma (11% to 19%, p0.0001), treatment for wheeze (15% to 26%, p0.0001), and admission for wheeze or other chest trouble (6% to 10%, p0.0001). The increase occurred both in children with viral wheeze (9% to 19%) and in those with the classic asthma pattern of wheezing with multiple triggers (6% to 10%). There was also an increase in transient early wheezers (3% to 5%), persistent wheezers (5% to 13%), and late-onset wheezers (6% to 8%), and in all severity groups. The increase could not be accounted for by putative household risk factors because these declined between the 2 years.The fact that all preschool wheezing disorders increased (including viral wheeze) makes it probable that factors unrelated to atopy are implicated in the changing epidemiology of wheeze in childhood.

The question "Has your child ever had wheezing or whistling in the chest at any time in the past?" is a simple and widely used proxy measure for the lifetime prevalence of asthma. Our aim was to test its validity in a longitudinal survey, comparing retrospective recall with prospective assessment of lifetime prevalence. A population-based cohort of 1,422 children, surveyed twice previously, was studied again at age 8-13 yrs by postal questionnaire using standardized questions from the International Study of Asthma and Allergies in Childhood (ISAAC). Of those traced (1,190) questionnaires were returned by 89%. The prevalence of current wheeze was higher than in the previous surveys (20.5% versus 12.4% and 12.5%). Reported "wheeze ever" increased significantly from survey 1 (15.6%) to survey 2 (22.4%) and survey 3 (39.2%) and was very similar to the cumulative lifetime prevalence assessed prospectively over three surveys (42.8%). The retrospective question had a good negative predictive value (97%) and a reasonable positive predictive value (65%) compared to prospective assessment. Children reporting "wheeze ever" (but not current wheeze) in surveys 1 and 2 had at survey 3 an asthma prevalence higher than never-wheezers but lower than current-wheezers. It is concluded that retrospective recall of wheeze at age 8-13 yrs is a valid proxy measure for the lifetime prevalence of wheeze.

This is the authors final draft of the version published as The Lancet, 2007, 370(9589), pp.717-719. The published paper can be accessed www.sciencedirect.com.

W. Cherniak, B. Dreifuss, J. Evert, M. Dacso, H.C. Lin, L. Loh; Bridge to Health Medical and Dental, Toronto, ON/CA, University of Arizona College of Medicine Tucson; Global Emergency Care Collaborative, Tucson, AZ/US, University of California San Francisco, San Francisco, CA/US, University of Texas Medical Branch, Galveston, TX/US, University of Pennsylvania School of Medicine, Philadelphia, PA/US, The 53rd Week Ltd., Vancouver, BC/CA

In 1995, a publicly funded pneumococcal vaccination program for 23-valent polysaccharide vaccine (PPV23) was introduced in Ontario. Conjugate vaccines were authorized in 2001 (PCV7), 2009 (PCV10) and 2010 (PCV13).From 1995-2011, active, population-based surveillance for invasive pneumococcal disease (IPD) was conducted in Metropolitan Toronto and Peel Region, Canada.6404 IPD cases were included. After PPV23 program implementation in 1995, IPD due to PPV23 strains decreased 49% in older adults prior to PCV7 introduction. Estimated PPV23 efficacy in vaccine eligible adults was 42.2% (95% CI; 28.6-53.2%). IPD incidence due to PCV7 serotypes in children5 years decreased significantly after PCV7 authorization and before introduction of a publicly funded PCV7 program. Seven years after PCV7 program implementation, the incidence of IPD due to PCV7 serotypes decreased to zero in children and by 88% in adults, however, overall IPD incidence remained unchanged in adults. In 2011, the incidence of IPD was 4.5 per 100,000 in adults aged 15-64 and 19.9 per 100,000 in adults aged over 65 years, with 45 serotypes causing disease. Between 1995 and 2011, the case fatality rate of IPD in adults decreased 2% per year (95% CI, -0.9% to -3.2%). In multivariable analysis, predictors of mortality included older age, chronic conditions, nursing home residence, current smoking, bacteraemia, and illness due to serotypes 3,11A, 19A, and 19F.While vaccination programs resulted in substantial public health benefits, herd immunity benefits of PCV7 were seen at low pediatric vaccination rates, and the case fatality rate of IPD has decreased, IPD will continue to be a cause of considerable morbidity and mortality in adults.

The Book of Luminaries contains two enigmatic details which can be compared to Iranian ideas: the concept of astronomical solar “gates,” and a sevenfold mythical geography in chapter 77. Although the document overall is highly indebted to Mesopotamian traditions, the source of these two details can better be explained as Iranian. The ultimate Mesopotamian origin of the astronomy cannot be gainsaid, but the exact formulations of some of the details found in the extant book may have been in dialogue with or shaped by Iranian scholarship. If so, further work on what this means for the interaction of systems and communities in the ancient Near East (which of course already includes things Persian) may be justified.

Respiratory inductive plethysmography (RIP) records movements of the rib cage (RC) and abdomen (AB). A calibration procedure is needed to determine their relative contribution to tidal volume. We evaluated the hypothesis that the relative contribution of the RC and AB could be defined from respiratory efforts made during a brief occlusion of the airways in 10 infants aged 6.5-19 months, who were studied in quiet sleep. Six occlusions were performed during tidal breathing, with and without a pneumotachograph (PNT) and face mask in place. We analyzed the periods of occluded respiratory effort when RC and AB were in opposite directions (paradoxical movements), plotting RC vs. AB and performing a least-squares linear regression to estimate the ratio of the coefficients of AB/RC. Multiple linear regression of AB and RC over tidal volume during about 100 seconds of tidal breathing provided a reference standard. A ratio of 1 means that AB and RC make equal contributions to tidal volume. The feasibility of the occlusion maneuver was poor; only 51% of occlusions with PNT and 54% without led to a paradoxical movement with a good fit (r > 0.9). The mean coefficient of variation (range) was 9.35% (3.9-15.3%) with PNT and 12.1% (2.5%-26.3%) without it. The accuracy was very poor, with the mean AB/RC value being 0.94 with occlusions and 2.39 with multiple linear regression. The mean difference was 1.45 (SD 0.80), yielding 95% confidence limits for the difference of 0.12-3.01. We concluded that, due to its very poor accuracy and feasibility, the occlusion technique is not a useful method to calibrate RIP in infancy.

This article presents the results of a survey of 99 practitioners that explored their attitudes related to the conflicting priorities of maintaining the principles of confidentiality, versus exercising one's duty to warn someone of danger. Social work practitioners face this dilemma in working with individuals who have HIV disease. When clients let workers know that they are engaging in unsafe sexual practices, and have not warned their partner of their HIV+ status, Practitioners are in a bind. Results show deep ambivalence in attitudes and actions. Discussion focuses on the dilemmas involved, and presents recommendations for practice.

Respiratory inductive plethysmography (RIP) is a simple technique for an objective, noninvasive assessment of thoracoabdominal asynchrony, which in turn is an indirect measure of airway obstruction. We evaluated different indices of asynchrony obtained by RIP before and after methacholine-induced airway obstruction. Bronchial obstruction was elicited by progressive doubling concentrations of methacholine until a > 15% fall in the transcutaneous oxygen tension (PtcO2) had developed. Maximal expiratory flow rates at functional residual capacity (FRC) (VmaxFRC) was obtained by the squeeze technique before and after the challenge. Fifteen infants with a history of wheezing were studied after sedation. Thoracoabdominal movements were recorded with RIP bands placed around either the upper or the lower ribcage (RC) and around the abdomen (AB). An inspiratory asynchrony index (IAI) and an expiratory asynchrony index (EAI) were calculated as determined by the lag of RC relative to AB at start of inspiration and of expiration, respectively. The total time in asynchrony (TTA: the percentage of time in which the RC and the AB signals were in opposite direction) and phi (an angle derived from a Lissajous loop) were also calculated. All subjects responded to the challenge. The median fall in PtcO2 following methacholine challenge was 23.6% and in VmaxFRC was 43%. A large scatter of baseline values was found for all indices with the exception of TTA. There was no correlation between TTA and age, length, or VmaxFRC. The IAI and EAI with the RC band in the upper position were the most sensitive indices, both within subjects (65% of the subjects had a significant change in IAI and 80% in EAI) and for the group as a whole (median values increased for IAI, P = 0.007, and for EAI, P = 0.017). TTA and phi were less sensitive, and a great discrepancy was observed between the two measurements. Poor results were obtained with the RC band in the lower position. No correlations were found between the changes in IAI and EAI, with the RC band around the lower chest and VmaxFRC. We conclude that IAI and EAI, measured with the RC band in the upper position and another band around the abdomen, can detect changes in thoracoabdominal asynchrony in most infants. The usefulness of assessing IAI and EAI in infants with acute lower airway obstruction needs to be determined.

BACKGROUND--The level of bronchial responsiveness in those with definite asthma correlates with disease severity and markers of airway inflammation. However, in population studies no clear distinction between normal and abnormal is found. Since the outcome of wheeze in early childhood is very variable, a marker of underlying airway inflammation would be of practical value. A stimulus acting indirectly may be more appropriate than one acting directly on smooth muscle. In this study the airway response to a direct (methacholine) and indirect (hypertonic saline) challenge have been compared in 5-6 year old children with past or present wheeze to see if symptom patterns or severity could be distinguished by either test. METHODS--Forty children with a wide spectrum of wheeze were monitored for a six month period after which their pattern and severity of symptoms were graded. Hypertonic saline and methacholine challenges were then performed on separate days. The response was assessed by both respiratory resistance (Rrs6) and transcutaneous oxygen (PTCO2). Atopic status was determined by IgE and skin prick tests. RESULTS--The results of both challenges were similar whether assessed by Rrs6 or PTCO2. There was no difference in the response to either methacholine or saline between different symptom patterns or severity grades, nor was there any correlation with either test to atopic status. CONCLUSIONS--Neither an indirect nor a direct challenge distinguished between past or present wheeze or degree of clinical severity in this group of children. Either wheezy children of this age do not have airway inflammation or bronchial responsiveness is not a marker for it.

Population-based data on influenza hospitalizations are unavailable in the United Kingdom, but they represent an essential component of health economic analyses that could support the use of vaccines and antiinfluenza drugs in healthy children. We collected data on hospitalizations for influenza infections among young children in Leicester, UK.This prospective, longitudinal, noninterventional single center study was conducted at the Children's Hospital in Leicester, which provides inpatient pediatric care to a total population of approximately 1 million. We studied children6 years of age between October 14, 2001, and June 30, 2002, who were admitted to the hospital with an acute respiratory tract illness, seizures, specified acute febrile gastrointestinal illness or any acute febrile illness or apnea or other life-threatening events in infants12 months of age. Nasopharyngeal swabs obtained within 24 h of hospital admission were examined for influenza, respiratory syncytial virus and human metapneumovirus by PCR.Of 7165 clinical episodes that were assessed in the Children's Hospital between October 1 and June 30, 2441 (34.1%) were caused by acute respiratory illness. Overall 33 (5.4%) of 613 children analyzed had an influenza A or B virus infection, including 19 (5.0%) of 381 children with acute respiratory illness and 14 (6.0%) of the remaining 232 children.Influenza is evidently an important cause of hospitalization among young children, even during limited outbreaks of influenza. Further analyses will enable us to estimate age-related admission rates for influenza and to compare the burden from influenza with that for respiratory syncytial virus and human metapneumovirus.

The purpose of this study is to evaluate the effectiveness of highly active antiretroviral therapy (HAART) in preventing mother-to-child transmission (PMTCT) of HIV in breastfeeding women in rural Zimbabwe. During a severe socio-economic crisis in 2005-2007, 82 eligible HIV-positive pregnant women between 14-36 weeks gestation were initiated on HAART with AZT/3TC/nelfinavir combination therapy at a rural hospital and continued through to six months post-partum. In addition, mothers also received intrapartum single-dose nevirapine (sdNVP). Infants received sdNVP/AZT in the first 72 hours and were assessed for HIV infection at six weeks of age. Results were compared to historical controls of HIV-positive pregnant women who received sdNVP only at the same center. Of the 67 infants with available data on HIV status at six weeks postpartum, three (4.4%) were HIV positive by HIV RNA assay in the HAART + sdNVP group compared to 49/297 (16.5%) in the sdNVP group (p = 0.01). HAART given to HIV-infected mothers in pregnancy and during breastfeeding along with intrapartum sdNVP resulted in a lower postnatal HIV transmission at six weeks postpartum compared to sdNVP treatment. Our HAART regimen demonstrates that PMTCT of HIV can be effective even during times of socioeconomic crisis in resource-poor rural settings.

The current hypothesis that human pulmonary alveolarization is complete by 3 years is contradicted by new evidence of alveolarization throughout adolescence in mammals. Objectives:We reexamined the current hypothesis using helium 3 (3He) magnetic resonance (MR) to assess alveolar size noninvasively between 7 and 21 years during which lung volume nearly quadruples. If new alveolarization does not occur alveolar size should increase to the same extent. Methods: Lung volumes were measured by spirometry and plethysmography in 109 healthy subjects aged 7 21 years. Using 3HeMR we determined two independent measures of peripheral airspace dimensions: apparent diffusion coefficient (ADC) of 3HeatFRC(n=109)and average diffusion distance of helium (X rms) by q space analysis (n =46). We compared the change in these parameters with lung growth against a model of lung expansion with no new alveolarization. Measurements and Main Results: ADC increased by 0.19 for every 1 increment in FRC (95 confidence interval [CI] 0.13 0.25) whereas the expected change in the absence of neoalveolarization is 0.41 (95 CI 0.31 0.52). Similarly increase of (X rms) with FRC was significantly less than the predicted increase in the absence of neoalveolarization. The number of alveoli is estimated to increase 1.94 fold (95 CI 1.64 2.30) across the age range studied. Conclusions: Our observations are best explained by postulating that the lungs grow partly by neoalveolarization throughout childhood and adolescence. This has important implications: developing lungs have the potential to recover fromearly life insults and respondto emerging alveolar therapies. Conversely drugs diseases or environmental exposures could adversely affect alveolarization throughout childhood. Copyright © 2012 by the American Thoracic Society.

Density-dependent expression of luminescence in Vibrio harveyi is regulated by the concentration of extracellular signal molecules (autoinducers) in the culture medium. A recombinant clone that restored function to one class of spontaneous dim mutants was found to encode a function required for the density-dependent response. Transposon Tn5 insertions in the recombinant clone were isolated, and the mutations were transferred to the genome of V. harveyi for examination of mutant phenotypes. Expression of luminescence in V. harveyi strains with transposon insertions in one locus, luxO, was independent of the density of the culture and was similar in intensity to the maximal level observed in wild-type bacteria. Sequence analysis of luxO revealed one open reading frame that encoded a protein, LuxO, similar in amino acid sequence to the response regulator domain of the family of two-component, signal transduction proteins. The constitutive phenotype of LuxO- mutants indicates that LuxO acts negatively to control expression of luminescence, and relief of repression by LuxO in the wild type could result from interactions with other components in the Lux signalling system.

An acute scrotum is defined as an acute painful swelling of the scrotum or its contents, accompanied by local signs or general symptoms. Early identification and skillful management of testicular torsion is critical, as it may threaten testicular viability and future fertility if not managed expediently and appropriately. The cremasteric reflex and testicular sonography are frequently used, yet imperfect, diagnostic tools in assessing for testicular torsion. Other emergent conditions include incarcerated inguinal hernia, Fournier's gangrene, and any form of genitourinary trauma until proven otherwise. This article reviews the evaluation and management of the acute scrotum in the emergency department.

Summary Density-dependent expression of luminescence in Vibrio harveyi is regulated by the concentration of an extracellular signal molecule (autoinducer) in the culture medium. A recombinant clone that restored function to one class of spontaneous dim mutants was found to encode functions necessary for the synthesis of, and response to, a signal molecule. Sequence analysis of the region encoding these functions revealed three open reading frames, two (luxL and luxM) that are required for production of an autoinducer substance and a third (luxN) that is required for response to this signal substance. The LuxL and LuxM proteins are not similar in amino acid sequence to other proteins in the database, but the LuxN protein contains regions of sequence resembling both the histidine protein kinase and the response regulator domains of the family of two–component, signal transduction proteins. The phenotypes of mutants with luxL, luxM and luxN defects indicated that an additional signal–response system controlling density-dependent expression of luminescence remains to be identified.

Neither the origin of leucocytes in the premature newborn airway nor their relationship to perinatal factors has been adequately determined. In order to sample airway cells, modified bronchoalveolar lavage was performed on 74 intubated infants of < 32 weeks' gestation and < 24 hours of age. Cells were counted, stained and, in a small separate group of six infants, four boys and two girls, probed for the Y chromosome with suitable control samples. Perinatal risk factors for increased airway cellularity were analysed by multiple regression. Premature rupture of membranes of more than 24 hours' duration was independently associated with increased numbers of airway leucocytes (n = 74). More than 90% of airway leucocytes from four boys with pulmonary inflammation were positive for the Y chromosome indicating that the cells were of fetal rather than maternal origin.

The efficacy of a new valved spacer device, the Babyhaler inhaler (Glaxo) for administering metered dose inhaler treatment via a facemask to infants was assessed. In a double blind, single dose study, salbutamol (800 micrograms) or placebo were given on separate days to 12 sedated, sleeping, wheezy infants during a symptom free interval. Lung function was measured before and after administration and the bronchial response to aerosol challenge with methacholine was then assessed using the squeeze technique. A small increase in heart rate and a drop in arterial oxygen tension followed salbutamol administration. No other change in lung volume or air flow obstruction was detected. Bronchial responsiveness decreased significantly after the administration of salbutamol by Babyhaler, the PC30 (provoking concentration of methacholine causing a 30% fall in maximal flow at functional residual capacity by the squeeze technique) increasing from a median of 3.8 g/l after placebo to 12.5 g/l after salbutamol. The Babyhaler is an effective device for administering bronchodilator to wheezy infants. The small scale of the response may be attributable to the uncertain effect of beta agonists in this population. Furthermore, pulmonary deposition of inhaled aerosols may be reduced in nose breathing, sleeping infants.

The aim of this study was to determine the effect of surfactant treatment on the number and distribution of inflammatory cells in bronchoalveolar lavage fluid (BALF) from mechanically ventilated preterm infants over the first week of life in relation to the subsequent development of chronic lung disease (CLD). The study included 25 babies who received surfactant on clinical grounds and 29 babies of similar severity who did not. BALF was collected on days 1, 3, 5, and 7 after birth. Cell counts were performed and differentials were calculated on 300 cells. CLD was equally common in both treatment groups. Of the 54 infants, 29 (53%) who developed CLD had a higher incidence of patent ductus arteriosus and air leak and needed a higher concentration of inspired oxygen on the fifth and seventh days of life. Babies who developed CLD had more polymorphonuclear leucocytes and fewer macrophages on days 5 and 7 than those who recovered. Surfactant treatment was associated with a higher total white cell count on day 3. Between days 3 and 7, macrophage numbers were higher in surfactant treated babies, whatever the pulmonary outcome. This data suggests that CLD was associated with persistence of high numbers of polymorphonuclear leucocytes in BALF at the end of the first week. Surfactant treatment caused a persistent increase in macrophage numbers. The association between persistent neutrophilia and CLD was unaffected by surfactant treatment.

The aim of this study was to compare the fall in transcutaneous oxygen tension (Ptco2) as an outcome measure during bronchial provocation with histamine, with changes in airway function measured by the squeeze technique in healthy infants and those with wheezing disorders. Ptco2 was measured during histamine challenge in 20 infants, aged 6–16 months, of whom 14 had recurrent cough or wheeze (lower respiratory illness, LRI), and 6 were healthy. All were symptom free at the time of testing. The minimum value of Ptco2, after each nebulization was compared with the minimum baseline value. The response to increasing concentrations of histamine was also assessed by measuring maximal flow at functional residual capacity (VmaxFRC) by the squeeze technique. The inhaled concentration of histamine causing a 30% fall in VmaxFRC was calculated to give the provoking concentration (PC30). Baseline VmaxFRC was lower in symptomatic infants (117 mL/s) than the normal infants (322 mL/s; P

Background—Handheld electronic spirometers provide the opportunity for more comprehensive monitoring of lung function at home than has hitherto been available. The aim of this study was to assess the quality of spirometric data collected at home by 90 asthmatic schoolchildren aged 7‐14 years. Methods—After training, children carried out twice daily recordings at home for four consecutive periods of 4 weeks using a data storage spirometer (Vitalograph), encouraged by 4-weekly visits from a research nurse. Compliance (proportion of blows recorded at correct time of day), technical quality (by machine criteria), and valid data recorded (the multiple of compliance and technical ability) were assessed. Results—Mean compliance declined from 81.4% to 70.4% (p

Purpose The purpose of this study is to describe the patterns of hospitalization for depression in the year after delivery in relation to social, demographic, and behavioral characteristics. Methods Data on births were linked to hospitalizations for depression over the subsequent year to describe the frequency and patterns of hospitalized postpartum depression among 2,355,886 deliveries in New York State from 1995 to 2004. We identified “definite postpartum depression” based on International Classification of Diseases (ICD) codes indicative of “mental disorders specific to pregnancy,” and “possible postpartum depression” by ICD codes for hospitalization with any depressive disorders. Results In New York State, we identified 1363 women (5.8 per 10,000) who were hospitalized with definite postpartum depression, and 6041 women (25.6 per 10,000) with possible postpartum depression, with lower risks in the New York City area. Postpartum depression was more common in later years and among mothers who were older, Black, smokers, lacking private insurance, and with multiple gestations, and was rarer among Asians. For possible postpartum depression, socioeconomic gradients were enhanced. Conclusions Risk of hospitalized postpartum depression is strongly associated with socioeconomic deprivation and varies markedly by ethnicity, with direct implications for screening and health services, also providing suggestions for etiologic studies.

Properdin, a serum glycoprotein, is an important component of innate immunity, the only known positive regulator of complement, acting as an initiation point for alternative pathway activation. As an X-linked protein, we hypothesized that properdin may play a modulatory role in the pathogenesis of viral wheeze in children, which tends to be more common and more severe in boys. We aimed to determine properdin levels in a community-based paediatric sample, and to assess whether levels of properdin were associated with childhood wheeze phenotypes and atopy. We studied 137 school-children aged 8-12 yrs, a nested sample from a cohort study. Properdin was measured by a commercial enzyme-linked immunoabsorbant assay. We assessed wheeze by questionnaire, validated it by a nurse-led interview and performed skin prick tests and a methacholine challenge in all children. Forty children (29%) reported current wheeze. Serum properdin levels ranged between 18 and 40 microg/ml. Properdin was not associated with age, gender, atopy, bronchial responsiveness, current wheeze (neither the viral wheeze nor multiple-trigger wheeze phenotype) or severity of wheeze, but was slightly lower in south Asian (median 21.8 microg/ml) compared with white children (23.3 microg/ml; p = 0.006). Our data make it unlikely that properdin deficiency is common in healthy children or that levels of properdin are a major risk factor for wheeze or atopy.

We compared the delivery of a micronized suspension of budesonide by a metered dose inhaler (MDI) with two different spacers (Aerochamber and Aerovent) and by two jet nebulizers (MAD2 and Ultravent) to a ventilated neonatal test-lung using a standard neonatal ventilator circuit. The combination of MDI and Aerochamber was significantly better at delivering budesonide to a filter in front of the test lung (14.2% of aerosolized dose) than were either the MDI and Aerovent (3.6%) or the Ultravent or MAD2 jet nebulizers (0.02% and 0.68% of initial reservoir dose). Of the droplets emerging from the MDI, Aerochamber, and ET tube, 18% of the initial dose was in droplets less than 4.7 microns. Assuming that the test-lung model accurately reflects in vivo deposition, the combination of MDI and Aerochamber appears to be an extremely effective way of delivering budesonide aerosol to ventilated newborn infants.