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Summary Introduction In our institution, patients with suspected pulmonary TB undergo multiple induced-sputum sampling for microscopy, culture and nucleic acid amplification (NAA) with the MTD ® Gen-probe assay. Those with negative induced-sputum results still suspected with TB are then referred for bronchoscopy. We sought to determine the diagnostic yield of bronchoscopy in these patients with negative initial induced-sputum results both via smear and NAA testing. Methods We identified 30 consecutive cases of suspected pulmonary TB between 2001 and 2007, who had undergone a diagnostic bronchoscopy after negative results on induced-sputum smears and the MTD ® Gen-probe on at least 2 samples. Results The cohort (M = 20 & F = 10) had a median age of 37 (range 16–85 yrs); were predominantly foreign born (27/30); HIV-negative (29/30) individuals with strongly positive TST's (mean 18 + 5 mm). Induced-sputum cultures were negative for M-TB in all patients after a full 60-day incubation period. BAL was culture positive for M-TB in 3/30 cases (10%) with 2 strains being pan-sensitive and the third being INH resistant. BAL microscopy with acid-fast smear ( n = 30) and BAL Gen-probe ( n = 23) were negative in all cases. A third of the patients (9/27, 33%) with negative bronchoscopy results were treated for culture negative TB. Treatment for latent TB was initiated in 5/27 (18%) individuals whereas 13/27 (48%) received no further treatment. Conclusion Bronchoscopy provided diagnostic confirmation of pulmonary TB in 10% of subjects at least 2 negative induced-sputum samples by smear microscopy and NAA testing.

Classic tissue effects of β(2)-adrenergic receptor activation include skeletal muscle glycogenolysis and vascular smooth muscle relaxation, factors relevant to obesity and hypertension, respectively. In a population-based study, we examined 2 common amino acid substitutions in the β(2)-adrenergic receptor gene (ADRB2) in relation to body composition and blood pressure. A cross-sectional analysis of 1893 African-descent men living in Tobago and participating in a prostate cancer screening study was performed. Body mass index, waist circumference, blood pressure, dual-energy x-ray absorptiometry body composition, and ADRB2 (Arg16Gly; Gln27Glu) genotype were determined. Twenty-six percent were obese (body mass index ≥30 kg/m(2)), and 50% were hypertensive. ADRB2 Arg16Gly and Gln27Glu alleles were in linkage disequilibrium (D' = 0.96, r(2) = 0.15). ADRB2 16Gly-containing and 27Glu-containing genotypes were equally frequent in low, medium, and high tertiles of percentage of body fat mass (16Gly-containing genotypes: 73.4%, 74.4%, and 74.5%, P(trend) = .66; 27Glu-containing genotypes: 27.6%, 23.8%, and 25.4%, P(trend) = .39) and in normal blood pressure, prehypertensive, and hypertensive men (16Gly-containing genotypes: 73.4%, 72.8%, and 74.4%, P(trend) = .61; 27Glu-containing genotypes: 25.6%, 24.1%, and 26.7%, P(trend) = .50). In a high-obesity and high-hypertension risk population with ancestry in common with African Americans, genetic variation defined by 2 common ADRB2 amino acid substitutions was not associated with body composition or hypertension.

BackgroundNocturnal oxyhaemoglobin desaturation is common in cystic fibrosis (CF) but the effect on quality of life (QoL) remains unknown.MethodsSixty stable CF outpatients with mean age 31±8years (mean±1SD), BMI 20.8±3.2kg/m2 and FEV1 42±13% predicted had arterial blood gas sampling, lung function testing, overnight pulse oximetry and completed the CF QoL questionnaire, Epworth Sleepiness Scale and Medical Research Council dyspnoea scale.Results11 (18%) of the CF patients were ‘desaturators,’ (SpO2

The clinical presentation of noncystic fibrosis bronchiectasis may be complicated by concomitant conditions, including gastro-oesophageal reflux (GOR). Increased acidic GOR is principally caused by gastro-oesophageal junction incompetence and may arise from lower oesophageal sphincter hypotension, including transient relaxations, hiatus hernia, and oesophageal dysmotility. Specific pathophysiological features which are characteristic of respiratory diseases including coughing may further increase the risk of GOR in bronchiectasis. Reflux may impact on lung disease severity by two mechanisms, reflex bronchoconstriction and pulmonary microaspiration. Symptomatic and clinically silent reflux has been detected in bronchiectasis, with the prevalence of 26 to 75%. The cause and effect relationship has not been established, but preliminary reports suggest that GOR may influence the severity of bronchiectasis. Further studies examining the implications of GOR in this condition, including its effect across the disease spectrum using a combination of diagnostic tools, will clarify the clinical significance of this comorbidity.

We investigated the breeding biology of the Brown Noddy Anous stolidus at its southern-most breeding locality, cold-temperate Gough Island (40°S) in the South Atlantic Ocean. We monitored 19 nests over three seasons for breeding schedules, and measured the growth of eight chicks and six fledglings during the 2005/06 breeding season. Across all seasons, egg-laying occurred between 2–12 December, mean incubation was 37 days and median hatch date was 15 January. Three late hatch dates suggest that replacement clutches can be laid if failure occurs early in the season. Chicks fledged after a mean of 46 days, but remained in the vicinity of the nest and were provisioned by adults for up to 11 days. Hatching success was 88%, fledging success 92% and breeding success 81%, which is higher than at most other sites. The size, chick growth-rates and pre-fledging fast displayed by Gough's Brown Noddies are similar to that of Brown Noddies breeding at other mid-latitude Atlantic locations. These similarities of these ...

The origin of the aluminum equivalent shield approximation in space radiation analysis can be traced back to its roots in the early years of the NASA space programs (Mercury, Gemini and Apollo) wherein the primary radiobiological concern was the intense sources of ionizing radiation causing short term effects which was thought to jeopardize the safety of the crew and hence the mission. Herein, it is shown that the aluminum equivalent shield approximation, although reasonably well suited for that time period and to the application for which it was developed, is of questionable usefulness to the radiobiological concerns of routine space operations of the 21st century which will include long stays onboard the International Space Station (ISS) and perhaps the moon. This is especially true for a risk based protection system, as appears imminent for deep space exploration where the long-term effects of Galactic Cosmic Ray (GCR) exposure is of primary concern. The present analysis demonstrates that sufficiently large errors in the interior particle environment of a spacecraft result from the use of the aluminum equivalent approximation, and such approximations should be avoided in future astronaut risk estimates. In this study, the aluminum equivalent approximation is evaluated as a means for estimating the particle environment within a spacecraft structure induced by the GCR radiation field. For comparison, the two extremes of the GCR environment, the 1977 solar minimum and the 2001 solar maximum, are considered. These environments are coupled to the Langley Research Center (LaRC) deterministic ionized particle transport code High charge (Z) and Energy TRaNsport (HZETRN), which propagates the GCR spectra for elements with charges (Z) in the range 1 ⩽ Z ⩽ 28 (H–Ni) and secondary neutrons through selected target materials. The coupling of the GCR extremes to HZETRN allows for the examination of the induced environment within the interior of an idealized spacecraft as approximated by a spherical shell shield, and the effects of the aluminum equivalent approximation for a good polymeric shield material such as generic polyethylene (PE). The shield thickness is represented by a 25 g/cm2 spherical shell. Although, one could imagine the progression to greater thickness, the current range will be sufficient to evaluate the qualitative usefulness of the aluminum equivalent approximation. Upon establishing the inaccuracies of the aluminum equivalent approximation through numerical simulations of the GCR radiation field attenuation for PE and aluminum equivalent PE spherical shells, we further present results for a limited set of commercially available, hydrogen rich, multifunctional polymeric constituents to assess the effect of the aluminum equivalent approximation on their radiation attenuation response as compared to the generic PE.

Summary Sauber-Schatz EK, Markovic N, Weiss HB, Bodnar LM, Wilson JW, Pearlman MD. Descriptive epidemiology of birth trauma in the United States in 2003. Paediatric and Perinatal Epidemiology 2010; 24: 116–124. The rate of birth trauma in the US has been reported to range between 0.2 and 37 birth traumas per 1000 births. Because of the minimal number of population-based studies and the inconsistencies among the published birth trauma rates, the rate of birth trauma in the US remains unclear. This is a cross-sectional study that was conducted using 890 582 in-hospital birth discharges from the 2003 Healthcare Cost and Utilization Project Kids' Inpatient Database. A neonate was defined as having birth trauma if their hospital discharge record contained an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code from 767.0 to 767.9. Weighted data were used to calculate rates for all birth traumas and specific types of birth traumas, and rates and odds ratios by demographic, hospital and clinical variables. Weighted data represented a national estimate of 3 920 787 in-hospital births. Birth trauma was estimated to occur in 29 per 1000 births. The three most frequently diagnosed birth traumas were injuries to the scalp, other injuries to the skeleton and fracture of the clavicle. Significant univariable predictors for birth trauma included male gender, Asian or Pacific Islander race, living in urban or wealthy areas, being born in Western, urban and/or teaching hospital, a co-diagnosis of high birthweight, instrument delivery, malpresentation and other complications during labour and delivery. Birth trauma risk factors including those identified in this study may be useful to consider during labour and delivery. In conclusion, additional research is necessary to identify ways to reduce birth trauma and subsequent infant morbidity and mortality.

An increase in edge area reduces the effective size of habitat fragments and thus the area available for habitat-interior specialists. However, it is unclear how edge effects compare at different ecotones in the same system. We investigated the response of a small mammal community associated with Afromontane forests to edge effects at three different habitat transitions: natural forest to grassland (natural edge, structurally different vegetation types), natural forest to mature plantation (human-altered edge, structurally similar vegetation types) and natural forest to harvested plantation (human-altered edge, structurally different vegetation types). We predicted that edge effects should be less severe at natural ecotones and at similarly structured contiguous vegetation types than human-altered ecotones and differently structured contiguous vegetation types, respectively. We found that forest species seemed to avoid all habitat edges in our study area. Surprisingly, natural edges supported a less diverse small mammal community than human-altered forest edges. However, edge effects were observed deeper into native forests surrounded by mature alien plantations (and more so at harvested plantations) than into native forests surrounded by native grasslands. The net effect of mature plantations was therefore to reduce the functional size of the natural forest by creating a larger edge. We suggest that when plantations are established a buffer zone of natural vegetation be left between natural forests and newly established plantations to mitigate the negative effects of plantation forestry.

Background: Whether autonomic dysfunction contributes to tachycardia in cystic fibrosis (CF) is unknown. Methods: Heart rate variability (HRV) was assessed to determine high frequency power and the low/high frequency power ratio (HF, LF/HF) as markers of vagal and sympathovagal balance, respectively, under spontaneous and controlled breathing (15 breaths per minute (bpm)) conditions in 17 CF and 17 healthy control subjects. Results: Under spontaneously breathing conditions, the CF group was tachycardic (75.4 ±11.2 vs 60.2 ±9.0 br/min P < 0.001) and tachypnoeic (22.6 ±5.8 vs 13.6 ±4.1 br/min, P= 0.001) compared with controls. No significant difference in HRV was observed between groups during spontaneous or controlled breathing. Coexistent diabetes mellitus and β2 agonist use were not associated with altered autonomic control. During controlled breathing, the CF group showed a negative correlation between forced expiratory volume in 1 s (FEV1) % predicted and HF power (P= 0.013, r=−0.59) and a positive correlation between FEV1 % predicted and LF/HF ratio (P= 0.002, r= 0.69) suggesting an exaggerated normal vagal response. Conclusion: CF patients have normal autonomic function.

Development of evidence-based practice requires investigation of the attitudes and needs of patients, families and healthcare professionals, particularly for sensitive subject areas. Cystic fibrosis (CF) is a recessively inherited life-limiting disorder resulting in early death. Patients with this condition generally expect that lung transplantation will be an available treatment option; however, this is uncertain. A dual approach to care that involves both preparing patients for transplant assessment, while simultaneously exploring acceptable palliative care options is needed. A survey amongst patients with CF, their families and health carers was conducted to understand their attitudes and needs in relation to end-of-life care. The survey encompassed five separate domains, with a total of 60 questions requiring approximately 20 min to complete. Of the 200 surveys sent to patients, 82 (41%) completed responses were received. The Institutional Ethics Committee received six complaints from families of seven patients (3.5% of those surveyed). This article explores the nature of the adverse responses to the survey. The majority of complaints were received from family members rather than from patients. Complaints described dissatisfaction with the topic, little warning about the study and felt it to be inappropriate for their family member’s level of health. Survey instruments used to determine attitudes and needs in relation to end-of-life patient care are likely to elicit adverse responses that should be reported in a similar way to other investigational studies. Also arising from adverse responses and the complaint process, is the impact of criticism on study researchers.

A rapid analytical procedure for the prediction of a micro-dosimeter response function in low Earth orbit (LEO), correlated with the Space Transportation System (STS, shuttle) Tissue Equivalent Proportional Counter (TEPC) measurements is presented. The analytical model takes into consideration the energy loss straggling and chord length distribution of the detector, and is capable of predicting energy deposition fluctuations in a cylindrical micro-volume of arbitrary aspect ratio (height/diameter) by incoming ions through both direct and indirect (ray) events. At any designated (ray traced) target point within the vehicle, the model accepts the differential flux spectrum of Galactic Cosmic Rays (GCR) and/or trapped protons at LEO as input. On a desktop PC, the response function of TEPC for each ion in the GCR/trapped field is computed at the average rate of 30 seconds/ion. The ionizing radiation environment at LEO is represented by O'Neill fs GCR model (2004), covering charged particles in the 1 less than or equal to Z less than or equal to 28. O'Neill's free space GCR model is coupled with the Langley Research Center (LaRC) angular dependent geomagnetic cutoff model to compute the transmission coefficient in LEO. The trapped proton environment is represented by a LaRC developed time dependent procedure which couples the AP8MIN/AP8MAX, Deep River Neutron Monitor (DRNM) and F10.7 solar radio frequency measurements. The albedo neutron environment is represented by the extrapolation of the Atmospheric Ionizing Radiation (AIR) measurements. The charged particle transport calculations correlated with STS 51 and 114 flights are accomplished by using the most recent version (2005) of the LaRC deterministic High charge (Z) and Energy TRaNsport (HZETRN) code. We present the correlations between the TEPC model predictions (response function) and TEPC measured differential/integral spectra in the lineal energy (y) domain for both GCR and trapped protons, with the conclusion that the model correctly accounts for the increase in flux at low y values where energetic ions are the primary contributor. We further discuss that, even with the incorporation of angular dependency in the cutoffs, comparison of the GCR differential/integral flux between STS 51 and 114 TEPC measured data and current calculations indicates that there still exists an underestimation by the simulations at low to mid range y values. This underestimation is partly related the exclusion of the secondary pion particle production from the current version of HZETRN.

An increasing trend in the use of contralateral prophylactic mastectomy (CPM) for the treatment of unilateral breast cancer has been observed nationally. The purpose of this study was to confirm this trend and to identify differences between the groups that chose unilateral mastectomy alone or with CPM. A prospectively maintained breast cancer database was retrospectively reviewed. Age, histologic grade, stage, education, family history, tumor receptor status, and use of immediate reconstruction were evaluated. Statistical analysis was performed by Fisher’s exact test, χ2 test, and Student’s t-test. Between 1998 and 2007, a total of 1639 women who selected UM and 201 who had UM and CPM for unilateral breast cancer were identified. An increasing trend in CPM was observed (6.5% in 1999 vs. 16.1% in 2007). The CPM group was significantly younger (mean age 47.8 vs. 55.1 years, P

Summary Objective Reduced bone mineral density (BMD) and increased rates of atraumatic fracture are observed in cystic fibrosis (CF) patients, causing increasing morbidity as this population ages. The study aimed to assess the safety, tolerability and effect on BMD of intravenous zoledronate in adults with CF and osteopaenia. Design Randomized, double-blind, placebo-controlled clinical trial. Setting Adult CF outpatient clinics at two hospitals. Patients Twenty-two non-transplanted CF patients aged ≥ 18 years with a bone densitometry T-score of

The role of combination antibiotic therapy with a beta-lactam and a fluoroquinolone for bacteremia caused by gram-negative bacilli, to our knowledge, has not been previously described. Much of the previous study of combination therapy has included beta-lactams and aminoglycosides. We conducted a large retrospective cohort study to evaluate 28-day all-cause mortality in patients with monomicrobial bacteremia due to aerobic gram-negative bacilli who received either a combination of beta-lactams and fluoroquinolones or beta-lactam monotherapy. We enrolled adult patients admitted to Mayo Clinic hospitals from 1 January 2001 to 31 October 2006 in the study. After stratification of patients by Pitt bacteremia scores, we used Cox regression models to estimate the hazard ratios (HR) for 28-day all-cause mortality after adjusting for the propensity to receive combination therapy. We identified 398 and 304 unique patients with bacteremia caused by gram-negative bacilli who received single and combination antibiotic therapy, respectively. In less severely ill patients with Pitt bacteremia scores of P = 0.044). In critically ill patients with Pitt bacteremia scores of ≥4, there was no difference in 28-day mortality between combination and single therapy (25.6% [23 of 90] versus 27.8% [22 of 79]; adjusted HR, 0.87; 95% CI, 0.47 to 1.62; P = 0.660). These findings were consistent for 14-day all-cause mortality. In this large cohort, we found for the first time that combination therapy with beta-lactams and fluoroquinolones was associated with a reduction in 28-day all-cause mortality among less severely ill patients with bacteremia caused by gram-negative bacilli.

Allogeneic (allo) hematopoietic stem cell transplantation is an effective therapy for hematological malignancies but it is limited by acute graft-versus-host disease (GVHD). Dendritic cells (DC) play a major role in the allo T cell stimulation causing GVHD. Current immunosuppressive measures to control GVHD target T cells but compromise posttransplant immunity in the patient, particularly to cytomegalovirus (CMV) and residual malignant cells. We showed that treatment of allo mixed lymphocyte cultures with activated human DC-depleting CD83 antibody suppressed alloproliferation but preserved T cell numbers, including those specific for CMV. We also tested CD83 antibody in the human T cell–dependent peripheral blood mononuclear cell transplanted SCID (hu-SCID) mouse model of GVHD. We showed that this model requires human DC and that CD83 antibody treatment prevented GVHD but, unlike conventional immunosuppressants, did not prevent engraftment of human T cells, including cytotoxic T lymphocytes (CTL) responsive to viruses and malignant cells. Immunization of CD83 antibody-treated hu-SCID mice with irradiated human leukemic cell lines induced allo antileukemic CTL effectors in vivo that lysed 51Cr-labeled leukemic target cells in vitro without further stimulation. Antibodies that target activated DC are a promising new therapeutic approach to the control of GVHD.

Purpose To describe the frequency of chemotherapy use for hormone receptor (HR)–positive, lymph node (LN)–negative breast cancer from 1997 to 2004 at eight National Comprehensive Cancer Network institutions, to explore whether chemotherapy use varied over time and between institutions, and to identify factors associated with the decision to forego chemotherapy. Patients and Methods Among women younger than age 70 years with HR-positive, LN-negative breast cancer measuring more than 1 cm, we analyzed the frequency of chemotherapy use on a yearly basis. A multivariable logistic regression model assessed the relationship between receipt of chemotherapy and year of diagnosis, institution, tumor features, and patient characteristics. Interaction terms were added to the model, and stratified analyses were conducted to further explore the determinants of chemotherapy use. Results Fifty-five percent of 3,190 women received chemotherapy. Chemotherapy use was less common for patients with 1.1- to 2-cm tumors than for patients tumors greater 2 cm (47% v 87%, respectively; P < .01) and for women age 60 to 69 years versus women younger than age 50 years (24% v 76%, respectively; P < .01). On multivariable analysis, predictors independently associated with receiving chemotherapy included larger tumor size, higher grade, human epidermal growth factor receptor 2 overexpression, younger age, and institution (P < .01 for all). Institutions exhibited dramatically different rates of chemotherapy use (from 46% to 65%) and patterns of change in chemotherapy use over time (from a 79% relative increase to a 22% relative decrease). Conclusion Although institutions seemed to agree that not all women with HR-positive, LN-negative breast cancer need chemotherapy, there did not seem to be consensus regarding which women should get chemotherapy. Only prospective randomized controlled trials will conclusively establish which subtypes of HR-positive, LN-negative breast cancer benefit from chemotherapy.

We investigate whether it is possible that viable microbes could have been transported to Earth from the planets in extra-solar systems by means of natural vehicles such as ejecta expelled by comet or asteroid impacts on such planets. The probabilities of close encounters with other solar systems are taken into account as well as the limitations of bacterial survival times inside ejecta in space, caused by radiation and DNA decay. The conclusion is that no potentially DNA/RNA life-carrying ejecta from another solar system in the general Galactic star field landed on Earth before life already existed on Earth, not even if microbial survival time in space is as long as tens of millions of years. However, if the Sun formed initially as a part of a star cluster, as is commonly assumed, we cannot rule out the possibility of transfer of life from one of the sister systems to us. Likewise, there is a possibility that some extra-solar planets carry life that originated in our solar system. It will be of great interest to identify the members of the Sun's birth cluster of stars and study them for evidence for planets and life on the planets. The former step may be accomplished by the GAIA mission, the latter step by the SIM and DARWIN missions. Therefore it may not be too long until we have experimental knowledge on the question whether the natural transfer of life from one solar system to another has actually taken place., Comment: 25 pages, 1 table, accepted to ApJ

Objective Improved life expectancy in cystic fibrosis (CF) alters the significance of developmentally relevant aspects such as sexual and reproductive health (SRH). Men with CF report parents are an important source of information about infertility, but parent perspectives remain unknown. The aim of this study was to systematically explore parents' knowledge, attitudes and behaviors regarding the SRH education of their sons. Patients and Methods Eligible participants were parents of boys with CF aged at least 6 years who completed a 61-item written questionnaire that was developed to measure parent knowledge and education about CF-specific aspects of SRH, and parent attitudes and behaviors about the CF-specific sexuality education of their sons. Results Eighty-four mothers (82%) and 64 fathers (70%) completed the questionnaire. All but one knew of probable infertility, being primarily informed at the time of diagnosis. Since then, 19% of parents reported subsequent discussions of SRH with their son's CF specialist, mostly initiated by parents. Adolescence was considered the most appropriate time for the initial education of boys. Sixty percent of parents worried how their sons would react. Ninety-five percent of parents said that they (alone or together with the CF specialist) should first inform their sons of probable infertility. Only 30% of parents were satisfied with their current knowledge. Conclusion These parents are well informed about male infertility in CF. However, they have had little opportunity for subsequent discussion of SRH with health professionals since their son's diagnosis. As boys mature, subsequent SRH discussions by health professionals with parents are indicated. Pediatr Pulmonol. 2008; 43:1107–1116. © 2008 Wiley-Liss, Inc.

For the success of NASA’s new vision for space exploration to Moon, Mars and beyond, exposures from the hazards of severe space radiation in deep space long duration missions is ‘a must solve’ problem. The payload penalty demands a very stringent requirement on the design of the spacecrafts for human deep space missions. The exploration beyond low Earth orbit (LEO) to enable routine access of space will require protection from the hazards of the accumulated exposures of space radiation, Galactic Cosmic Rays (GCR) and Solar Particle Events (SPE), and minimizing the production of secondary radiation is a great advantage. There is a need to look to new horizons for newer technologies. The present investigation revisits electrostatic active radiation shielding and explores the feasibility of using the electrostatic shielding in concert with the state-of-the-art materials shielding and protection technologies. The full space radiation environment has been used, for the first time, to explore the feasibility of electrostatic shielding. The goal is to repel enough positive charge ions so that they miss the spacecraft without attracting thermal electrons. Conclusions are drawn for the future directions of space radiation protection.

Lead is stored in the skeleton and can serve as an endogenous source for many years. Lead may influence the risk of fracture, through direct effects on bone strength or indirectly by disturbing neuromuscular function and increasing the risk of falls. The objective of this analysis is to test the hypothesis that women with higher blood lead levels experience higher rates of falls and fracture. This was a prospective cohort study of 533 women 65-87 yr of age enrolled in the Study of Osteoporotic Fractures at two U.S. research centers (Baltimore, MD; Monongahela Valley, PA) from 1986 to 1988. Blood lead levels (in microg/dl) were measured in 1990-1991 by atomic absorption spectrophotometry and classified as "low" (or=3; lower 15th percentile, referent); "medium" (4-7); or "high" (or=8; upper 15th percentile). Total hip BMD was measured by DXA twice, 3.55 yr apart. Information on falls was collected every 4 mo for 4 yr. Incident nonspine fractures were identified and confirmed over 10 yr. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% CI of fracture. Generalized estimating equations were used to calculate the incident rate ratio of falls (95% CI). The mean blood lead level was 5.3 +/- 2.3 (SD) microg/dl (range, 1-21 microg/dl). Baseline BMD was 7% lower in total hip and 5% lower in femoral neck in the highest compared with lowest blood lead group (p0.02). Hip bone loss tended to be greater in the high lead group, but differences were not significant. In multivariable adjusted models, women with high blood lead levels had an increased risk of nonspine fracture (HR = 2.50; 95% CI = 1.25, 5.03; p trend = 0.016) and higher risk of falls (incident rate ratio = 1.62; 95% CI = 1.07, 2.45; p trend = 0.014) compared with women with lowest lead level. Blood lead levels are associated with an increased risk of falls and fractures, extending the negative health consequences of lead to include osteoporotic fractures.

We investigated primary moult and morphometrics in the Green-winged Pytilia Pytilia melba during a six-month period (May–October) in central South Africa. A total of 157 pytilias were captured; 80 (51.0%) of these were in active primary moult during all months of the study. The Underhill-Zucchini model was not applicable for determining moult duration (start and end dates) due to the great variation in moult timing and because moulting may often be suspended. We suggest that this is due to factors other than low food availability.Ostrich 2008, 79(1): 87–90

The spectrum of diseases collectively known as pulmonary fibrosis does not have reliable therapeutic options. Many treatment protocols have been the subject of clinical trials, resulting in few significant improvements in outcome. Recently, cellular mechanisms have been the focus of investigations in progenitor cell studies, suggesting an immunomodulatory role for mesenchymal stem cells. The possible role of fibrogenic cytokines and the use of antagonist molecules are promising for future therapies. A range of anti-inflammatory treatments, including macrolide antibiotics, may also hold promise. When medical therapy has been unsuccessful in altering the course of the disease, lung transplantation may offer a significant survival advantage. Improvement in pre-transplant assessment and postoperative care, combined with more effective immunosuppressive regimes, has seen survival rates of 40% after 5 years. New options for therapy will lead to improved survival in coming years.

Purpose Multiple studies have found an association between the prompt initiation of empirically-appropriate antimicrobial therapy and improved patient outcomes. Such empiric-antimicrobial therapy is often broad; however, once the patient's infectious syndrome, microbiology, and susceptibilities are more defined, it is important to refine antimicrobial therapy. Despite the potential benefits of an “antimicrobial de-escalation” approach, it may be difficult to enforce in clinical practice. Mayo Clinic's Computer-Based Antimicrobial Monitoring System (CBAM) is a medical-informatics tool that was used to assist in this endeavor. This study evaluates the hypothesis that CBAM can enhance the de-escalation of vancomycin and broad-spectrum combination antimicrobial therapy. Methods Hospitalized patients at the Mayo Clinic were screened from January through June 2006 using rule-based algorithms incorporated by CBAM. Interventions were performed by physicians and pharmacists as pertinent. These patients were compared with a historical group of patients obtained by CBAM reporting capabilities. De-escalation rates and mean duration of antimicrobial therapy were compared between groups. Results Vancomycin de-escalation rates significantly improved from 33% to 68% with intervention ( P = 0.001). In addition, the average duration of therapy was decreased from 10.4 ± 7.3 days to 7.7 ± 2.4 days among patients who underwent vancomycin de-escalation per recommendation ( P = 0.014). Conclusions Utilizing the Mayo Clinic's CBAM system to identify potential patients for de-escalation is a unique approach and was successful at improving adherence to vancomycin de-escalation.

This study identifies clinical and pathologic factors predictive of havingor =4 involved axillary lymph nodes in breast cancer patients with a positive sentinel node. These factors may influence radiation therapy decisions.We reviewed the records of 201 patients with positive SLN who underwent axillary dissection; 34 of these patients hador =4 positive axillary lymph nodes. Factors associated withor = 4 lymph nodes were evaluated by chi(2) test, and multivariate logistic regression model was used to identify independent factors.On univariate analysis, presence of lymphovascular space invasion, extracapsular extension, increased number of positive SLN, increased size of tumor, macrometastases within the SLN, and decreased number of negative SLN were all significantly associated with havingor = 4 involved axillary lymph nodes. On multivariate analysis, presence of extracapsular extension (odds ratio [OR] = 3.76, P = 0.004), increased number of positive SLN (OR = 3.99, P = 0.006), increased size of tumor (OR = 3.33, P = 0.011 for size of 2.1 to 5 cm and OR = 8.28, P = 0.018 for size5 cm), and decreased number of negative SLN (OR = 2.62, P = 0.037) were found to be significant.We have identified primary tumor and SLN variables that predict for a greater probability of having a significant burden of residual disease in the axilla that may affect treatment recommendations.

Background: The clinical benefits of domiciliary non-invasive positive pressure ventilation (NIV) have not been established in cystic fibrosis (CF). We studied the effects of nocturnal NIV on quality of life (QoL), functional and physiological outcomes in CF subjects with awake hypercapnia (arterial carbon dioxide pressure Paco 2 >45 mm Hg). Methods: In a randomised, placebo controlled, crossover study, eight subjects with CF, mean (SD) age 37 (8) years, body mass index 21.1 (2.6) kg/m2, forced expiratory volume in 1 s 35 (8)% predicted and Paco 2 52 (4) mm Hg received 6 weeks of nocturnal (1) air (placebo), (2) oxygen and (3) NIV. The primary outcome measures were CF specific QoL, daytime sleepiness and exertional dyspnoea. Secondary outcome measures were awake and asleep gas exchange, sleep architecture, lung function and peak exercise capacity. Results: Compared with air, NIV improved the chest symptom score in the CF QoL Questionnaire (mean difference 10; 95% CI 5 to 16; p = 0.002) and the transitional dyspnoea index score (mean difference 3.1; 95% CI 1.2–5.0; p = 0.01). It reduced maximum nocturnal pressure of transcutaneous CO 2 (Ptcco 2 mean difference −17 mm Hg; 95% CI −7 to −28 mm Hg; p = 0.005) and increased exercise performance on the Modified Shuttle Test (mean difference 83 m; 95% CI 21 to 144 m; p = 0.02). NIV did not improve sleep architecture, lung function or awake Paco 2 . Conclusion: 6 weeks of nocturnal NIV improves chest symptoms, exertional dyspnoea, nocturnal hypoventilation and peak exercise capacity in adult patients with stable CF with awake hypercapnia. Further studies are required to determine whether or not NIV can improve survival.

The 3DHZETRN code, with improved neutron and light ion (Z≤2) transport procedures, was recently developed and compared to Monte Carlo (MC) simulations using simplified spherical geometries. It was shown that 3DHZETRN agrees with the MC codes to the extent they agree with each other. In the present report, the 3DHZETRN code is extended to enable analysis in general combinatorial geometry. A more complex shielding structure with internal parts surrounding a tissue sphere is considered and compared against MC simulations. It is shown that even in the more complex geometry, 3DHZETRN agrees well with the MC codes and maintains a high degree of computational efficiency.

Context: The Radiation Assessment Detector (RAD) on the Mars Science Laboratory (MSL) has been measuring the radiation environment on the surface of Mars since August 6th 2012. MSL-RAD is the first instrument to provide detailed information about charged and neutral particle spectra and dose rates on the Martian surface, and one of the primary objectives of the RAD investigation is to help improve and validate current radiation transport models. Aims: Applying different numerical transport models with boundary conditions derived from the MSL-RAD environment the goal of this work was to both provide predictions for the particle spectra and the radiation exposure on the Martian surface complementing the RAD sensitive range and, at the same time, validate the results with the experimental data, where applicable. Such validated models can be used to predict dose rates for future manned missions as well as for performing shield optimization studies. Methods: Several particle transport models (GEANT4, PHITS, HZETRN/OLTARIS) were used to predict the particle flux and the corresponding radiation environment caused by galactic cosmic radiation on Mars. From the calculated particle spectra the dose rates on the surface are estimated. Results: Calculations of particle spectra and dose rates induced by galactic cosmic radiation on the Martian surface are presented. Although good agreement is found in many cases for the different transport codes, GEANT4, PHITS, and HZETRN/OLTARIS, some models still show large, sometimes order of magnitude discrepancies in certain particle spectra. We have found that RAD data is helping to make better choices of input parameters and physical models. Elements of these validated models can be applied to more detailed studies on how the radiation environment is influenced by solar modulation, Martian atmosphere and soil, and changes due to the Martian seasonal pressure cycle. By extending the range of the calculated particle spectra with respect to the experimental data additional information about the radiation environment is gained, and the contribution of different particle species to the dose is estimated.

The Gough Moorhen is endemic to Gough Island and is classified by the IUCN as Threatened. We present several observations of Gough Moorhens preying on introduced House Mice Mus musculus and on eggs and chicks of burrow-nesting procellariiform seabirds. The incidence of egg predation is almost certainly related to incubation breaks or abandonment. We estimate that Moorhens could access and depredate unattended eggs of at least five species but levels of predation appear to be low and are unlikely to affect population parameters of impacted species. Moorhens hunting live mice and scavenging carcasses presents a significant conservation concern. A possible eradication of mice from Gough Island is likely to employ poisons that are toxic to the Moorhens. Therefore secondary poisoning of Moorhens, by eating poisoned mice, is a threat to the Gough Moorhens. An eradication effort will be required to take appropriate mitigation measures. The introduced Gough Moorhen population on Tristan da Cunha serves as an ex situ population and could, if required, be used to re-stock Gough.

With increasing numbers of cystic fibrosis (CF) patients surviving to adulthood, issues related to vocation inevitably arise and warrant specific attention. We examined the percentage of participants with CF currently working and explored risk factors for work disability among adults with CF.We recruited 50 consecutive patients from an adult cystic fibrosis service. Demographic, employment history, illness severity indicators and CF-attributed work disability factors were evaluated. Demographic risk factors for work disability using the illness severity measures of FEV(1), S-K score, CRDQ, and recent hospitalisation as independent variables were determined.Factorial analysis of a disability index (DI) indicated no dependency on FEV(1) or S-K score, but dependency on quality of life indices (p0.05), age (p0.05) and hospital admission rate (p0.05). Hours worked per week were dependent on quality of life (p0.01) (mastery of disease domain), fewer hospital admissions (p0.01) and age (p0.05). Sixty-eight percent of the sample reported that CF resulted in significant impediments to employment. However, few had sought vocational guidance (6%).Determinants of workforce participation shows that hours worked and perceived disability are more dependent on mastery of disease, age, and time in hospital, than on clinical severity scores. Health professionals may assist productivity through career counselling or tailored programs.

Results for the radiation environment to be found on the planet Mars due to Galactic Cosmic Rays (GCR) and Solar Particle Events (SPE) has been obtained. Primary particle environments computed for Martian conditions are transported within the Mars atmosphere, modeled in a time-dependent way in terms of density, pressure, and temperature vs. altitude, down to the surface, with topography and backscattering patterns taken into account. The atmospheric chemical and isotopic composition has been modeled over results from the in-situ Viking Lander measurements for both major and minor components. The surface topography has been determined by using a model based on the data provided by the Mars Orbiter Laser Altimeter (MOLA) instrument on board the Mars Global Surveyor (MGS) spacecraft. The surface itself has been modeled in both the dry (‘regolith’) and volatile components. Mars regolith composition has been modeled based on the measurements obtained with orbiter and lander spacecraft from which an average composition has been derived. The volatile inventory properties, both in the regolith and in the seasonal and perennial polar caps, has been taken into account by modeling the deposition of volatiles and its variations with geography and time all throughout the Martian year, from results from imaging data of orbiter spacecraft. Results are given in terms of fluxes, doses and LET, for most kinds of particles, namely protons, neutrons, alpha particles, heavy ions, pions, and muons for various soil compositions.

In view of manned missions targeted to the Moon, for which radiation exposure is one of the greatest challenges to be tackled, it is of fundamental importance to have available a tool, which allows the determination of the particle flux and spectra at any time and at any point of the lunar surface. With this goal in mind, a new model of the Moon's radiation environment due to Galactic Cosmic Rays (GCR) and Solar Particle Events (SPE) has been developed. Primary particles reach the lunar surface, and are transported all throughout the subsurface layers, with backscattering patterns taken into account. The surface itself has been modeled as regolith and bedrock, with composition taken from the results of the instruments flown on the Apollo missions. Subsurface environments like lava tubes have been considered in the analysis. Particle transport has been performed with both deterministic and Monte Carlo codes with an adaptation for planetary surface geometry. Results are given in terms of fluxes, doses and LET, for most kinds of particles for various kinds of soil and rock chemical compositions.

We investigated the influence of forest fragment size and isolation on the bird assemblages in the species- and endemic-rich sand forests of the Maputaland Centre of Endemism, southern Mozambique. Point-centre surveys were conducted across 12 sand forest patches that varied in size and isolation. Patch size and isolation had little influence on bird species richness, but the number of individuals decreased significantly with increasing isolation. Furthermore, bird abundances were correlated to a combination of the size and isolation of patches. Many forest specialists, in particular large-bodied frugivores, were highly sensitive to reduced patch size and increased distances between patches. Further fragmentation of the landscape may therefore impair the ability of these forests to support viable populations of forest specialists. Ostrich 2007, 78(1): 37–42

The HZETRN code has been identified by NASA for engineering design in the next phase of space exploration highlighting a return to the Moon in preparation for a Mars mission. In response, a new series of algorithms beginning with 2005 HZETRN, will be issued by correcting some prior limitations and improving control of propagated errors along with established code verification processes. Code validation processes will use new/improved low Earth orbit (LEO) environmental models with a recently improved International Space Station (ISS) shield model to validate computational models and procedures using measured data aboard ISS. These validated models will provide a basis for flight-testing the designs of future space vehicles and systems of the Constellation program in the LEO environment.

Anisotropies in the low Earth orbit (LEO) radiation environment were found to influence the thermoluminescence detectors (TLD) dose within the (International Space Station) ISS 7A Service Module. Subsequently, anisotropic environmental models with improved dynamic time extrapolation have been developed including westward and northern drifts using AP8 Min & Max as estimates of the historic spatial distribution of trapped protons in the 1965 and 1970 era, respectively. In addition, a directional dependent geomagnetic cutoff model was derived for geomagnetic field configurations from the 1945 to 2020 time frame. A dynamic neutron albedo model based on our atmospheric radiation studies has likewise been required to explain LEO neutron measurements. The simultaneous measurements of dose and dose rate using four Liulin instruments at various locations in the US LAB and Node 1 has experimentally demonstrated anisotropic effects in ISS 6A and are used herein to evaluate the adequacy of these revised environmental models.

Extensively drug-resistant (XDR) tuberculosis (TB) is an unfortunate by-product of mankind's medical and pharmaceutical ingenuity during the past 60 years. Although new drug developments have enabled TB to be more readily curable, inappropriate TB management has led to the emergence of drug-resistant disease. Extensively drug-resistant TB describes Mycobacterium tuberculosis that is collectively resistant to isoniazid, rifampin, a fluoroquinolone, and an injectable agent. It proliferates when established case management and infection control procedures are not followed. Optimized treatment outcomes necessitate time-sensitive diagnoses, along with expanded combinations and prolonged durations of antimicrobial drug therapy. The challenges to public health institutions are immense and most noteworthy in underresourced communities and in patients coinfected with human immunodeficiency virus. A comprehensive and multidisciplinary case management approach is required to optimize outcomes. We review the principles of TB drug resistance and the risk factors, diagnosis, and managerial approaches for extensively drug-resistant TB. Treatment outcomes, cost, and unresolved medical issues are also discussed.

G551D a CFTR mutation results in impaired chloride channel function in Cystic Fibrosis (CF).Ivacaftor, a CFTR potentiating agent improves FEV1 and sweat chloride(SC) but its effect on exercise is unproven. Aims and Objectives: To evaluate exercise capacity in response to correction of the chloride channelopathy with ivacaftor. Methods: In a placebo-controlled crossover study (EndX) of ivacaftor over 4 months with a 3 month open label extension (OLE) we performed cardiopulmonary exercise tests (CPET) at six time points on twenty patients. Primary outcome was VO2max as a percentage of baseline at EndX and OLE periods. Results: FEV1, SC and exercise time showed a statistically significant difference versus placebo at EndX. Other parameters (VO2max) improved only after OLE.VO2 max & exercise time increased versus baseline at EndX and OLE in treated patients.FEV1 and SC also improved as expected. Conclusions: Early improvements in FEV1 and SC only improved exercise time, but prolonged treatment resulted in elevated VO2max.Results suggest other factors (likely muscular) add to cardiorespiratory improvements seen with ivacaftor treatment.

The dynamics of predator-prey pursuit appears complex, making the development of a framework explaining predator and prey strategies problematic. We develop a model for terrestrial, cursorial predators to examine how animal mass modulates predator and prey trajectories and affects best strategies for both parties. We incorporated the maximum speed-mass relationship with an explanation of why larger animals should have greater turn radii; the forces needed to turn scale linearly with mass whereas the maximum forces an animal can exert scale to a 2/3 power law. This clarifies why in a meta-analysis, we found a preponderance of predator/prey mass ratios that minimized the turn radii of predators compared to their prey. It also explained why acceleration data from wild cheetahs pursuing different prey showed different cornering behaviour with prey type. The outcome of predator prey pursuits thus depends critically on mass effects and the ability of animals to time turns precisely. DOI: http://dx.doi.org/10.7554/eLife.06487.001, eLife digest A pursuit between a predator and its prey involves complex strategies. Prey often make sudden sharp turns when running to evade a predator. Any predator that cannot turn quickly enough will have to run further to catch up with the prey again, thus potentially allowing the prey to pull away from the predator. The timing of these turns is crucial; if the prey turns when the predator is too far away, the predator can cut the corner off the turn and catch up with the prey more easily. The speed at which animals can turn depends on the forces involved in cornering, and larger animals need to produce greater forces for any given turn. However, larger animals can apply relatively less force than smaller animals for turns and so cannot turn as rapidly. The effect of the relationship between mass and turning ability on the strategies used during land-based pursuits had not been investigated. Wilson et al. have now created a mathematical model that considers how the mass of a predator and its prey influences the course and strategies used in a land-based pursuit. The model is based in part on a mathematical problem called the ‘homicidal chauffeur game’, where a car driver attempts to run over a pedestrian. Wilson et al.'s model predicts that chases between large predators and smaller prey should feature frequent sharp turns, as the prey try to exploit their superior turning ability. However, when the predators and prey are of similar size, the prey gain little or no advantage from executing high-speed turns. Indeed, as turning slows the prey down, turning may often be disadvantageous, and so fewer turns should be seen during a pursuit. The predictions of the model were compared with the pursuit strategies of wild cheetahs, which were studied using collars equipped with tags to measure acceleration as the predators chased prey of different sizes—from hares to large antelopes called gemsboks. The tracking data confirmed the predictions of the model; thereby revealing that body mass and the ability of animals to choose when best to turn strongly determine the outcome of predator-prey pursuits. DOI: http://dx.doi.org/10.7554/eLife.06487.002

The understanding of future space radiation environments is an important goal for space mission operations, design, and risk assessment. We have developed a solar cycle statistical model in which sunspot number is coupled to space-related quantities, such as the galactic cosmic radiation (GCR) deceleration potential (phi) and the mean occurrence frequency of solar particle events (SPEs). Future GCR fluxes were derived from a predictive model, in which the temporal dependence represented by phi was derived from GCR flux and ground-based Climax neutron monitor rate measurements over the last four decades. These results showed that the point dose equivalent inside a typical spacecraft in interplanetary space was influenced by solar modulation by up to a factor of three. It also has been shown that a strong relationship exists between large SPE occurrences and phi. For future space exploration missions, cumulative probabilities of SPEs at various integral fluence levels during short-period missions were defined using a database of proton fluences of past SPEs. Analytic energy spectra of SPEs at different ranks of the integral fluences for energies greater than 30 MeV were constructed over broad energy ranges extending out to GeV for the analysis of representative exposure levels at those fluences. Results will guide the design of protection systems for astronauts during future space exploration missions.

Airway remodelling refers to the structural changes that occur in the airway wall in asthma. These include epithelial hyperplasia and metaplasia, subepithelial fibrosis, muscle cell hyperplasia and angiogenesis. These structural changes result in thickening of the airway wall, airway hyperresponsiveness (AHR), and a progressive irreversible loss of lung function. The precise sequence of events that take place during the remodelling process and the mechanisms regulating these changes remain poorly understood. It is thought that airway remodelling is initiated and promoted by repeated episodes of allergic inflammation that damage the surface epithelium of the airway. However, other mechanisms are also likely to contribute to this process. Moreover, the interrelationship between airway remodelling, inflammation and AHR has not been clearly defined. Currently, there are no effective treatments that halt or reverse the changes of airway remodelling and its effects on lung function. Glucocorticoids have been unable to eliminate the progression of remodelling changes and there is limited evidence of a beneficial effect from other available therapies. The search for novel therapies that can directly target individual components of the remodelling process should be made a priority. In this review, we describe the current understanding of the airway remodelling process and the mechanisms regulating its development. The impact of currently available asthma therapies on airway remodelling is also discussed.

A supply-side analysis of the average stock returns over 1926-2004 helps us see how components that include real earnings growth and the price-earnings ratio have contributed to the average total return. The long-run sustainable average equity return can be expressed as a benchmark expected equity return. An innovation is that investors can use a supply-side model as a disciplined framework for estimating average equity returns over much shorter periods than the 80-year sample analyzed.

It has long been recognized that galactic cosmic rays are of such high energy that they tend to pass through available shielding materials resulting in exposure of astronauts and equipment within space vehicles and habitats. Any protection provided by shielding materials result not so much from stopping such particles but by changing their physical character in interaction with shielding material nuclei forming, hopefully, less dangerous species. Clearly, the fidelity of the nuclear cross-sections is essential to correct specification of shield design and sensitivity to cross-section error is important in guiding experimental validation of cross-section models and database. We examine the Boltzmann transport equation which is used to calculate dose equivalent during solar minimum, with units (cSv/yr), associated with various depths of shielding materials. The dose equivalent is a weighted sum of contributions from neutrons, protons, light ions, medium ions and heavy ions using the ICRP-60 LET dependent quality factors. We investigate the sensitivity of dose equivalent calculations due to errors in nuclear fragmentation cross-sections. We do this error analysis for all possible projectile-fragment combinations (14,365 such combinations) to estimate the sensitivity of the shielding calculations to errors in the nuclear fragmentation cross-sections. Numerical differentiation with respect to the cross-sections will be evaluated in a broad class of materials including polyethylene, aluminum and copper. We will identify the most important cross-sections to ensure adequate experimental study and evaluate their impact on propagated errors in shielding estimates.