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Summary Background Whole breast irradiation delivered once per day over 3–5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. Methods We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5–8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov , NCT00282035 . Findings Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3–9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9–4·0) in the APBI group and 2·8% (1·8–3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84–1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p Interpretation External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. Funding Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.

The fog of uncertainty surrounding COVID‐19 has begun to clear as information about the virus accumulates from around the world. Governments have had varying responses to the pandemic, indicative of this uncertainty. The Australian government's restrictions have to date been effective in slowing spread of viral infections but may have had unintended consequences on other health conditions as a result. Paediatric emergency department presentations have decreased as people are reluctant to leave home and risk contracting the virus whilst attending hospital.1 These delays to presentation have the potential to increase morbidity and mortality from non‐COVID‐19 related diseases. Our institution is the largest children's hospital in Australia and performs between 350 and 400 appendectomies each year. Using appendicitis as a bellwether, we wanted to see if there was evidence for later presentations in our hospital.

Environmental disturbances seem to be increasing in frequency and impact, yet we have little understanding of the belowground impacts of these events. Soil fauna, while widely acknowledged to be important drivers of biogeochemical function, soil structure and sustainability, and trophic interactions, are understudied compared to other belowground organisms such as archaea, bacteria, and fungi. In this review we summarize the current state of knowledge of soil fauna as it relates to and is influenced by various disturbances. We focus our review on three main natural and anthropogenic disturbance types: 1) natural disturbances, including damage from wind and flooding; 2) invasive species, including above and belowground flora and fauna; and 3) climate change impacts on the atmosphere and temperature. We do not address the impacts of wildfires, forestry, agricultural practices, mining, or human-caused pollution, as these topics have all been covered in other works. We highlight knowledge gaps and suggest future avenues of research, with hope that the importance of soil fauna and their influences on ecosystems will be given greater emphasis in future research.

Abdominal pain is among the most common presenting complaints observed in paediatric emergency departments. One uncommon cause of this presentation in the paediatric population is a trichobezoar. Within the broader literature, this pathology has almost exclusively been observed in teenagers with a concomitant psychiatric diagnosis. We present a rare case of an alternate aetiology – a child in whom iron deficiency anaemia (IDA) precipitated pica behaviours that subsequently led to the formation of a trichobezoar requiring surgical removal. Although rare, this case highlights the importance of considering iron deficiency anaemia induced pica as a precipitant of trichobezoar in the surgical work-up of children presenting to a health facility with abdominal pain. Keywords: Pica, Trichobezoar, Iron deficiency anaemia

From Freud through to modern times researchers have aimed to develop a clearer understanding of therapeutic processes and outcomes. Despite this continued interest in the field, the representation of psychotherapy processes and the applicability of research findings and recommendations to the therapeutic field continue to prove difficult. Quantitative and qualitative studies each purport to provide answers, however, they differ greatly in their research methods and underlying ontological and epistemological views. Efficacy and effectiveness studies and the measures of statistical significance and clinical significance are explored with their inherent strengths and weaknesses highlighted. This paper presents the view that research into psychotherapy should enhance the experiences of both the therapist and client. For this to be achieved it is recommended that quantitative and qualitative data, or objective and subjective experiences, should collude rather than collide.

The purpose of this study was to determine the predictors and outcomes of pregnant women with vaginal-rectal carriage of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). We performed an unmatched 1:4 case-control study with two control groups (13 CA-MRSA cases, 52 methicillin-sensitive S. aureus (MSSA) controls, and 52 S. aureus-negative controls) via a retrospective medical record review. We found that CA-MRSA cases were 12.5 times significantly less likely to be colonized with group B streptococci (GBS) compared with MSSA controls in multivariable analyses. When we compared MSSA patients with S. aureus-negative patients, we found that MSSA patients were 4.5 times significantly more likely to be colonized with GBS and 11 times significantly more likely to have a postpartum fever > or = 100.4 degrees F in multivariable analyses. Traditional risk factors for hospital-associated MRSA do not appear to predict vaginal-rectal CA-MRSA carriage in pregnant women. Instead, CA-MRSA carriage is significantly associated with lack of GBS carriage. Additional microbiologic studies and epidemiologic studies are needed to clarify the relationship between S. aureus and GBS, given that these two colonizing organisms have the potential to become pathogens.

The leukotriene modifiers are a novel generation of therapeutic agents in the treatment of allergic asthma. However, the mechanisms by which the cysteinyl (cys) leukotrienes (LTs) participate in allergen-induced airway eosinophilia and airway hyperresponsiveness (AHR) are still unclear. In the present study, we have investigated the role of cys-LTs in ovalbumin (OVA)-induced airway responses in a murine model of asthma. Montelukast (3 or 10 mg/kg), a selective cys-LT1 receptor antagonist, reduced airway eosinophilia and AHR after OVA challenge. The levels of interleukin (IL)-5 and eotaxin in the bronchoalveolar lavage fluid (BALF) from montelukast-treated (3 mg/kg) mice were unaffected, although a decrease in IL-5 was observed with a dose of 10 mg/kg. LTD4 (50 ng) instilled intranasally to immunized mice augmented macrophages in the BALF, but in conjunction with OVA challenge it caused BALF eosinophilia and neutrophilia when given before challenge and BALF neutrophilia but not eosinophilia when given 2 h after challenge. However, there were no increases of IL-5 or eotaxin in BALF following LTD4 treatment. Repeated instillations of LTD4 to immunized mice, mimicking allergen challenge, did not induce AHR but in conjunction with OVA challenge LTD4 enhanced AHR. These results indicate that allergen-induced eosinophilia and AHR are in part mediated by the cys-LT1 receptor, and that, although LTD4 alone has no effect on airway eosinophilia, in conjunction with antigenic stimulation it potentiates the degree of airway inflammation and AHR.

Background A multi-institutional phase II trial was performed to assess a hypofractionated accelerated radiotherapy regimen for early stage non-small cell lung cancer (NSCLC) in an era when stereotactic body radiotherapy was not widely available. Methods Eighty patients with biopsy-proven, peripherally located, T1-3 N0 M0 NSCLC were enrolled. Eligible patients received 60 Gy in 15 fractions using a three-dimensional conformal technique without inhomogeneity correction. The gross tumour volume (GTV) was the primary tumor only, and the planning target volume (PTV) margin was 1.0 to 1.5cm. The primary endpoint was the 2-year primary tumor control rate. Toxicities were measured using the Common Terminology Criteria for Adverse Events version 3.0. Results The median follow-up of patients was 49 months (range = 21-63 months). The median age of patients was 75.9 years. The actuarial rate of primary tumor control was 87.4% (95% confidence interval [CI] = 76.2% to 93.5%) at 2 years. Overall survival was 68.7% (95% CI = 57.2% to 77.6%) at 2 years. The actuarial rates of developing regional and distant relapse at 2 years were 8.8% (95% CI = 4.1% to 18.7%) and 21.6% (95% CI = 13.5% to 33.5%), respectively. Tumor size greater than 3cm was associated with an increased risk of developing distant relapse (hazard ratio = 3.11; 95% CI = 1.30 to 7.42; two-sided log-rank test P = .007). The most common grade 3+ toxicities were fatigue (6.3%), cough (7.5%), dyspnea (13.8%), and pneumonitis (10.0%) Conclusions Conformal radiotherapy to a dose of 60 Gy in 15 fractions resulted in favorable primary tumor control and overall survival rates in patients with T1-3 N0 M0 NSCLC. Severe toxicities were uncommon with this relatively simple treatment technique.

BackgroundAcute exposure to chlorine (Cl2) gas causes epithelial injury and airway dysfunction. γδ T cells are present in the mucosal surface of the airways and may contribute to the injury/repair response of the epithelium.MethodsC57Bl/6J (wild type) and TCR-δ-/-mice exposed to Cl2(400 ppm) for 5 minutes underwent measurements of airway responses to i.v. methacholine (MCh) at 1, 3, and 5 days after exposure. Bronchoalveolar lavage was performed to determine epithelial and leukocyte counts, and protein content. Tissue repair was assessed by proliferating cell nuclear antigen (PCNA) immunoreactivity and by expression of keratinocyte growth factor (KGF) mRNA by real-time PCR.ResultsWild type mice developed a greater degree of airway hyperresponsiveness to MCh at 1 day post exposure to Cl2compared with TCR-δ-/-mice. Epithelial cell counts in BAL after Cl2exposure were greater in TCR-δ-/-mice, but macrophages showed a later peak and granulocyte numbers were lower in TCR-δ-/-than in wild type mice. Both groups had increased levels of total protein content in BAL after Cl2exposure that resolved after 3 and 5 days, respectively. Epithelial proliferating cell nuclear antigen staining was increased at 1 and 3 days post exposure and was similar in the two groups. KGF mRNA was constitutively expressed in both groups and did not increase significantly after Cl2but expression was lower in TCR-δ-/-mice.ConclusionThe severity of airway epithelial injury after Cl2is greater in TCR-δ-/-mice but the inflammatory response and the change in airway responsiveness to methacholine are reduced. The rates of epithelial regeneration are comparable in both groups.

Annual genitourinary radiation oncology meetings aim to assist in the dissemination of knowledge that may affect current practice. We aim to measure changes in practice approaches that have occurred while these meetings have been conducted.A previously published survey from 2002 was sent to all genitourinary radiation oncologists in Ontario. Six prostate cancer patient scenarios were used: three definitive (low risk, intermediate risk, high risk), and three post-operative (extracapsular extension, margin positive, slowly rising PSA). There were 21 responders from seven cancer centers.Using biological equivalent dose (BED), there is significant dose escalation in 2005, particularly for intermediate risk patients (mean BED 73.0 Gy2 in 2002 versus 76.1 Gy2 in 2005, p=0.0003). There has been a corresponding move away from the use of neoadjuvant hormones in these patients (2002: 62% versus 2005: 24%, p=0.0097). More accurate prostate localization using fiducials is more common, leading to less use of rectal barium and urethrograms in the simulation process. In the definitive settings there is more utilization of rigid immobilization and more complex treatment delivery including intensity modulated radiotherapy. There is also greater use of multileaf collimation, electronic portal imaging and dose volume histograms in 2005 compared with 2002.There have been significant changes in the way that prostate cancer is managed with radiotherapy in Ontario between 2002 and 2005. Dose escalation and more complex treatment planning is widely evident.

Purpose: Current estimates of the proportion of cancer patients who will require radiotherapy (RT) are based almost entirely on expert opinion. The objective of this study was to calculate the proportion of incident cases of cervical cancer that should receive RT by application of an evidence-based approach. Methods and Materials: A systematic review of the literature was done to identify indications for RT for cervical cancer and to ascertain the level of evidence that supported each indication. A survey of Canadian gynecologic oncologists and radiation oncologists who treat cervical cancer was done to determine the level of acceptance of each indication among doctors who practice in the field. An epidemiologic approach was then used to estimate the incidence of each indication for RT in a typical North American population of patients with cervical cancer. Results: The systematic review of the literature identified 29 different indications for RT for cervical cancer. The majority of the 75 experts who responded to the mail survey stated that they “usually” or “always” recommended RT in all but one of the clinical situations that were identified as indications for RT on the basis of the systematic review. The analysis of epidemiologic data revealed that, in a typical North American population, 65.4% ± 2.5% of cervical cancer cases will develop one or more indications for RT at some point in the course of the illness, 63.4% ± 2.3% will develop indications for RT as part of their initial management, and 2.0% ± 0.9% will develop indications for RT for progressive or recurrent disease. The effects of variations in case mix on the need for RT was examined by sensitivity analysis, which suggested that the maximum plausible range for the appropriate rate of utilization of RT was 54.3% to 67.9%. The proportion of cases that required RT was stage dependent: 10.6% ± 1.2% in Stage IA, 74.9% ± 1.3% in Stage IB, 100% in Stages II and III, and 97.2% ± 1.1% in Stage IV. Conclusions: This evidence-based estimate of the appropriate rate of use of RT for cervical cancer adds to the growing pool of knowledge about the need for RT that will ultimately provide a rational basis for long-term planning for RT programs and for auditing access to RT in the general population.

Background: Glucocorticoids inhibit allergen-induced airway eosinophilia and airway hyperresponsiveness (AHR). Whether glucocorticoids mediate their effects on AHR by inhibiting eotaxin and IL-5, 2 of the principal mediators of eosinophilia, or through IL-13, an important mediator of AHR, has not been established. Objective: We sought to investigate the effects of glucocorticoids on airway eosinophilia and the expression of IL-5, eotaxin, and IL-13 in relation to the induction of AHR in a murine model of allergic asthma. Methods: Dexamethasone (4 mg/kg) and mAbs against eotaxin (80 μg/kg) and IL-5 (100 μg/kg) singly and in combination were administered to immunized mice before antigen challenge. Airway responsiveness to methacholine was measured in anesthetized and mechanically ventilated animals. Eotaxin, IL-5, and IL-13 in bronchoalveolar lavage fluid (BALF), lung homogenates, or both were measured by means of ELISA. Results: A single antigen challenge induced AHR that lasted at least 10 days. Eotaxin protein and mRNA levels increased in lung tissue but not in BALF after challenge. IL-5 protein and mRNA levels increased both in BALF and in lung tissue. Dexamethasone reduced airway eosinophilia, AHR, and protein and mRNA for eotaxin and IL-5. Anti-murine eotaxin and anti-IL-5 antibodies alone and in combination reduced the ovalbumin-induced airway eosinophilia significantly but failed to inhibit AHR. Both dexa-methasone and anti-IL-5/anti-eotaxin inhibited the increases in lung IL-13 levels after ovalbumin challenge to a similar extent. Conclusion: These findings suggest that the inhibition of AHR by the glucocorticoid dexamethasone does not appear to be explained by effects on eosinophilia, eotaxin, IL-5, or IL-13. (J Allergy Clin Immunol 2003;111:1049-61.)

Exposure to chlorine gas (Cl2) causes occupational asthma that we hypothesized occurs through the induction of airway inflammation and airway hyperresponsiveness by oxidative damage. Respiratory mechanics and airway responsiveness to methacholine were assessed in A/J mice 24 hours after a 5-minute exposure to 100, 200, 400, or 800 ppm Cl2 and 2 and 7 days after inhalation of 400 ppm Cl2. Airway responsiveness was higher 24 hours after 400 and 800 ppm Cl2. Responsiveness after inhalation of 400 ppm Cl2 returned to normal by 2 days but was again elevated at 7 days. Airway epithelial loss, patchy alveolar damage, proteinaceous exudates, and inflammatory cells within alveolar walls were observed in animals exposed to 800 ppm Cl2. Macrophages, granulocytes, epithelial cells, and nitrate/nitrite levels increased in lung lavage fluid. Increased inducible nitric oxide synthase expression and oxidation of lung proteins were observed. Epithelial cells and alveolar macrophages from mice exposed to 800 ppm Cl2 stained for 3-nitrotyrosine residues. Inhibition of inducible nitric oxide synthase with 1400W (1 mg/kg) abrogated the Cl2-induced changes in responsiveness. We conclude that chlorine exposure causes functional and pathological changes in the airways associated with oxidative stress. Inducible nitric oxide synthase is involved in the induction of changes in responsiveness to methacholine.

Exogenous surfactant administration in patients with the acute respiratory distress syndrome is currently being evaluated, although resource limitations and the potential expense are existing concerns. Previous in vitro and in vivo studies have shown that substances such as polyethylene glycol (PEG) added to exogenous surfactant improved the function of the surfactant. Based on these data, we hypothesized that PEG would augment surfactant function in an adult rabbit model of lung injury induced by lung lavage and mechanical ventilation, and that this would be accomplished by altering surfactant metabolism. Contrary to our hypothesis, however, mean Pa(O(2)), Pa(CO(2)), and peak inspiratory pressures values 3 h after treatment were significantly worse in the surfactant + PEG treatment groups compared with the surfactant alone groups. These effects were observed for two different doses of surfactant tested. Lavage analyses after sacrifice showed that animals given PEG with their surfactant had significantly lower total and large aggregate surfactant pool sizes compared with animals given surfactant alone. We conclude that in this lung injury model, PEG attenuated surfactant responses, suggesting that further preclinical studies are required before testing this approach in humans.

Accidental chlorine (Cl2) gas inhalation is a common cause of acute airway injury. However, little is known about the kinetics of airway injury and repair after Cl2 exposure. We investigated the time course of airway epithelial damage and repair in mice after a single exposure to a high concentration of Cl2 gas. Mice were exposed to 800 ppm Cl2 gas for 5 minutes and studied from 12 hrs to 10 days post-exposure. The acute injury phase after Cl2 exposure (≤ 24 hrs post-exposure) was characterized by airway epithelial cell apoptosis (increased TUNEL staining) and sloughing, elevated protein in bronchoalveolar lavage fluid, and a modest increase in airway responses to methacholine. The repair phase after Cl2 exposure was characterized by increased airway epithelial cell proliferation, measured by immunoreactive proliferating cell nuclear antigen (PCNA), with maximal proliferation occurring 5 days after Cl2 exposure. At 10 days after Cl2 exposure the airway smooth muscle mass was increased relative to controls, suggestive of airway smooth muscle hyperplasia and there was evidence of airway fibrosis. No increase in goblet cells occurred at any time point. We conclude that a single exposure of mice to Cl2 gas causes acute changes in lung function, including pulmonary responsiveness to methacholine challenge, associated with airway damage, followed by subsequent repair and airway remodelling.