A first look at relative survival by stage for colorectal and lung cancers in Canada.

Monitoring and reporting on cancer survival provides a mechanism for understanding the effectiveness of Canada's cancer care system. Although 5-year relative survival for colorectal cancer and lung cancer has been previously reported, only recently has pan-Canadian relative survival by stage been analyzed using comprehensive registry data. This article presents a first look at 2-year relative survival by stage for colorectal and lung cancer across 9 provinces. As expected, 2-year age-standardized relative survival ratios (arsrs) for colorectal cancer and lung cancer were higher when the cancer was diagnosed at an earlier stage. The arsrs for stage i colorectal cancer ranged from 92.2% in Nova Scotia [95% confidence interval (ci): 88.6% to 95.1%] to 98.4% in British Columbia (95% ci: 96.2% to 99.3%); for stage iv, they ranged from 24.3% in Prince Edward Island (95% ci: 15.2% to 34.4%) to 38.8% in New Brunswick (95% ci: 33.3% to 44.2%). The arsrs for stage i lung cancer ranged from 66.5% in Prince Edward Island (95% ci: 54.5% to 76.5%) to 84.8% in Ontario (95% ci: 83.5% to 86.0%). By contrast, arsrs for stage iv lung cancer ranged from 7.6% in Manitoba (95% ci: 5.8% to 9.7%) to 13.2% in British Columbia (95% ci: 11.8% to 14.6%). The available stage data are too recent to allow for meaningful comparisons between provinces, but over time, analyzing relative survival by stage can provide further insight into the known differences in 5-year relative survival. As the data mature, they will enable an assessment of the extent to which interprovincial differences in relative survival are influenced by differences in stage distribution or treatment effectiveness (or both), permitting targeted measures to improve population health outcomes to be implemented.

Minimally constrained model of self-organized helical states in reversed-field pinches.

We show that the self-organized single-helical-axis (SHAx) and double-axis (DAx) states in reversed field pinches can be reproduced in a minimally constrained equilibrium model using only five parameters. This is a significant reduction on previous representations of the SHAx which have required an infinite number of constraints. The DAx state, which has a nontrivial topology, has not previously been reproduced using an equilibrium model that preserves this topological structure. We show that both states are a consequence of transport barrier formation in the plasma core, in agreement with experimental results. We take the limit of zero pressure in this work, although the model is also valid for finite pressure.

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes.

BACKGROUND: The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. AIM: To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. METHODS: A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. FINDINGS: In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. CONCLUSION: The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine.

Identification of dynamically distinct subpopulations of T lymphocytes that are differentially affected by HIV.

We examined the effects of human immunodeficiency virus infection on the turnover of CD4 and CD8 T lymphocytes in 17 HIV-infected patients by 30 min in vivo pulse labeling with bromodeoxyuridine (BrdU). The percentage of labeled CD4 and CD8 T lymphocytes was initially higher in lymph nodes than in blood. Labeled cells equilibrated between the two compartments within 24 h. Based on mathematical modeling of the dynamics of BrdU-labeled cells in the blood, we identified rapidly and slowly proliferating subpopulations of CD4 and CD8 T lymphocytes. The percentage, but not the decay rate, of labeled CD4 or CD8 cells in the rapidly proliferating pool correlated significantly with plasma HIV RNA levels for both CD4 (r = 0.77, P < 0.001) and CD8 (r = 0.81, P < 0.001) T cells. In six patients there was a geometric mean decrease of greater than 2 logs in HIV levels within 2 to 6 mo after the initiation of highly active antiretroviral therapy; this was associated with a significant decrease in the percentage (but not the decay rate) of labeled cells in the rapidly proliferating pool for both CD4 (P = 0.03) and CD8 (P < 0.001) T lymphocytes. Neither plasma viral levels nor therapy had an effect on the decay rate constants or the percentage of labeled cells in the slowly proliferating pool. Monocyte production was inversely related to viral load (r = -0.56, P = 0.003) and increased with therapy (P = 0.01). These findings demonstrate that HIV does not impair CD4 T cell production but does increase CD4 and CD8 lymphocyte proliferation and death by inducing entry into a rapidly proliferating subpopulation of cells.

A single-substrate model to interpret intra-annual stable isotope signals in tree-ring cellulose.

The carbon and oxygen stable isotope composition of wood cellulose (delta(13)C(cellulose) and delta(18)O(cellulose), respectively) reveal well-defined seasonal variations that contain valuable records of past climate, leaf gas exchange and carbon allocation dynamics within the trees. Here, we present a single-substrate model for wood growth to interpret seasonal isotopic signals collected in an even-aged maritime pine plantation growing in South-west France, where climate, soil and flux variables were also monitored. Observed seasonal patterns in delta(13)C(cellulose) and delta(18)O(cellulose) were different between years and individuals, and mostly captured by the model, suggesting that the single-substrate hypothesis is a good approximation for tree ring studies on Pinus pinaster, at least for the environmental conditions covered by this study. A sensitivity analysis revealed that the model was mostly affected by five isotopic discrimination factors and two leaf gas-exchange parameters. Modelled early wood signals were also very sensitive to the date when cell wall thickening begins (t(wt)). Our model could therefore be used to reconstruct t(wt) time series and improve our understanding of how climate influences this key parameter of xylogenesis.

The effects of wearing an Ankle Stabilizing Orthosis (ASO) Ankle Brace on ankle joints kinetics and kinematics during a basketball rebounding task.

Following an ankle injury, athletes sometimes brace the injured ankle in hopes of minimizing the likelihood of suffering a recurring injury. This study aims to evaluate the effects of wearing an Ankle Stabilizing Orthosis (ASO) ankle brace unilaterally on the dominant side on bilateral ankle joint kinetics and kinematics and peroneus longus EMG activity. Since a significant proportion of ankle injuries in basketball occur during rebounding, data was collected during a simulated rebounding task. Rebounding is defined as the act of retrieving a missed shot attempt. Subjects oftentimes jump vertically to acquire the basketball as it rebounds from the backboard or rim. Sixteen subjects participated in the study (11 males, 5 females; mean age = 26.94 years, SD = 5.32; mean height 1.72 m, SD = 0.08; mean weight 73.95 kg, SD = 13.68). Participants completed the rebounding task in braced (ASO) and unbraced (UB) conditions. Ankle and foot inversion angles, ankle inversion moments and peroneus longus EMG activity were recorded and analysed to determine the effects of wearing an ankle brace unilaterally. In the dominant limb, when compared to UB, ASO reduced ankle and foot inversion, and increased ankle inversion moments. No significant differences were observed in peroneus longus EMG activity. In the non-dominant limb, no significant differences were observed for any of the parameters. These results suggest that wearing an ASO ankle brace on the dominant ankle reduces maximum ankle and foot inversion angles without posing an increased risk to the unbraced leg. However, the increased ankle inversion moments in the braced ankle suggest that there are adjustments regarding force distribution, perhaps due to the restricted range of motion.

Comparison of 3 ankle braces in reducing ankle inversion in a basketball rebounding task.

Lateral ankle injury incidence rates are very high in the sport of basketball, with a significant proportion occurring during rebounding. Ankle braces are often used as preventative and rehabilitative techniques in the hope of minimizing the likelihood of experiencing excessive ankle inversion. This study aims to evaluate the effect of different ankle braces in preventing ankle inversion during a basketball rebounding task. Sixteen subjects participated in the study (11 males, 5 females; mean age = 26.94 years, SD = 5.32; mean height 1.72 m, SD = 0.08; mean weight 73.95 kg, SD = 13.68). Participants performed a simulated rebounding task in multiple braced conditions: unbraced (UB), Ossur Formfit (OF), Talarmade Ankleguard Air/Gel Stirrup (TAG) and Bauerfeind Malleoloc (BF). Ankle and foot inversion angles, ankle inversion moments and peroneus longus EMG activity were recorded and analysed to determine the effectiveness of each condition to resist inversion. All braced conditions reduced ankle and foot inversion angles compared to UB. In the non-dominant limb, OF showed reduced maximum ankle inversion compared to BF (non-dominant mean difference = 0.630°, p < 0.001) and reduced foot inversion compared to TAG (non-dominant mean difference = 0.966°, p = 0.035). Compared to UB, OF and TAG increased ankle inversion moments in the dominant ankle and showed decreases in the non-dominant ankle. BF reduced mean peak peroneus longus EMG activity compared to all other trials. Whilst statistically significant differences that were demonstrated between several braced conditions are relatively small, they are clinically significant knowing that the maximum barefoot inversion whilst standing is less than 17 degrees.

Hygienic behaviour selection via freeze-killed honey bee brood not associated with chalkbrood resistance in eastern Australia.

Hygienic behaviour is a social immune response in honey bees shown to help provide resistance to honey bee pests and diseases. A survey of hygienic behaviour and brood diseases was conducted on 649 colonies in eastern Australia to initiate a selective breeding program targeting disease resistance and provide a level of resistance to Varroa (Varroa destructor Anderson and Trueman and V. jacobsoni Oudemans) mites should they become established in Australia. The test population showed a remarkably high baseline level of hygienic behaviour with 17% of colonies meeting or exceeding breeding selection thresholds. Colonies belonging to a breeding program were 5.8 times more likely to be highly hygienic and colonies headed by queens raised from hygienic queen mothers were 2.2 times more likely. Nectar availability (nectar yielding flowering plants within honey bee forage range) influenced hygienic behaviour expression but was not a significant predictor of level of hygienic behaviour. Surprisingly, hygienic behaviour was not a significant predictor of the presence of infection of the honey bee brood disease chalkbrood (Ascosphaera apis) and was not influential in predicting severity of chalkbrood infection in surveyed honey bee colonies. This study, along with reports from commercial beekeepers that chalkbrood infection is on the rise, warrants a deeper exploration of the host-pathogen relationship between Apis mellifera and Ascosphaera apis in Australia.

Heterozygosity for a defective gene for CC chemokine receptor 5 is not the sole determinant for the immunologic and virologic phenotype of HIV-infected long-term nonprogressors.

HIV-1-infected long-term nonprogressors are a heterogeneous group of individuals with regard to immunologic and virologic markers of HIV-1 disease. CC chemokine receptor 5 (CCR5) has recently been identified as an important coreceptor for HIV-1 entry into CD4+ T cells. A mutant allele of CCR5 confers a high degree of resistance to HIV-1 infection in homozygous individuals and partial protection against HIV disease progression in heterozygotes. The frequency of CCR5 heterozygotes is increased among HIV-1- infected long-term nonprogressors compared with progressors; however, the host defense mechanisms responsible for nonprogression in CCR5 heterozygotes are unknown. We hypothesized that nonprogressors who were heterozygous for the mutant CCR5 gene might define a subgroup of nonprogressors with higher CD4+ T cell counts and lower viral load compared with CCR5 wild-type nonprogressors. However, in a cohort of 33 HIV-1-infected long-term nonprogressors, those who were heterozygous for the mutant CCR5 gene were indistinguishable from CCR5 wild-type nonprogressors with regard to all measured immunologic and virologic parameters. Although epidemiologic data support a role for the mutant CCR5 allele in the determination of the state of long-term nonprogression in some HIV-1- infected individuals, it is not the only determinant. Furthermore, long-term nonprogressors with the wild-type CCR5 genotype are indistinguishable from heterozygotes from an immunologic and virologic standpoint.

Cost-utility of adjuvant hormone therapies with aromatase inhibitors in post-menopausal women with breast cancer: upfront anastrozole, sequential tamoxifen-exemestane and extended tamoxifen-letrozole.

This evaluation adapts a previous Canadian analysis of upfront and sequential adjuvant AI strategies in postmenopausal women with breast cancer to a Belgian perspective and includes an extended aromatase inhibitor (AI) strategy. A Markov model calculated monthly costs and outcomes in a hypothetical cohort of postmenopausal women with early-stage breast cancer. Baseline event rates and hazard ratios were derived from the Arimidex, Tamoxifen Alone or in Combination trial, International Exemestane Study and MA.17 trials. The analysis took a Belgian healthcare payer perspective with a 20-year time horizon. Costs and outcomes were discounted by 3%. Costs are in 2005 Euros. The cost-utility of all three strategies was favourable (<30,000 euros per QALY gained). Based on indirect comparisons using tamoxifen (TAM) alone as a common comparator, sequential TAM-AI was less costly and more effective than upfront or extended strategies. All three AI strategies were cost-effective alternatives to TAM alone, but sequential TAM-AI appears to be the economically preferred strategy.

Reproducibility of the Balance Evaluation Systems Test (BESTest) and the Mini-BESTest in school-aged children.

This study evaluated the intra-rater, inter-rater and test-retest reproducibility of the Full-BESTest and Mini-BESTest when assessing postural control in children. Thirty-four children aged 7-17 years participated in intra-rater and inter-rater evaluation, and 22 children repeated assessment six weeks later for evaluation of test-retest reliability. Postural control was assessed using the Full Balance Evaluation Systems Test (Full-BESTest) and the short-form Mini-BESTest. Intra-rater, inter-rater and test-retest reproducibility were examined using video assessment. Test-retest reproducibility was also assessed in real-time. Reproducibility was examined by agreement and reliability statistics. Agreement was calculated using percentage of agreement, Limits of Agreement and Smallest Detectable Change. Reliability was calculated using Intra-class Correlation Coefficients. Results showed that the reliability of Total Scores was excellent for the Full-BESTest for all conditions (all ICCs>0.82), whereas the Mini-BESTest ranged from fair to excellent (ICC=0.56-0.86). Percentage of Domain Scores with good-excellent reliability (ICCs>0.60) was slightly higher for the Full-BESTest (66%) compared to the Mini-BESTest (59%). Smallest Detectable Change scores were good to excellent for the Full-BESTest (2%-6%) and for the Mini-BESTest (5%-10%) relative to total test scores. Both the Full-BESTest and Mini-BESTest can discriminate postural control abilities within and between days in school-aged children. The Full-BESTest has slightly better reproducibility and a broader range of items, which could be the most useful version for treatment planning. We propose minor modifications to improve reproducibility for children, and indicate the modified version by the title Kids-BESTest. Future psychometric research is recommended for specific paediatric clinical populations.

Incidence of IDDM in Montreal by ethnic group and by social class and comparisons with ethnic groups living elsewhere.

We examined the incidence of insulin-dependent diabetes mellitus (IDDM) among children aged 0-14 yr in Montreal by social class and by ethnic group from 1971 to 1985. There was a slightly higher risk in wealthier as opposed to poorer classes. This income gradient was more marked in younger than in older children. Children of French extraction had about two-thirds the risk of IDDM of children of other origins, mainly British and other European. This mimics the patterns of risk in Europe, where France is reported to have lower rates than does Britain and Scandinavia. The absolute levels of risks among French Canadian and Jewish Canadian children were about double those reported from France and Israel, respectively. These various results are compatible with the hypothesis that both genetic and environmental factors influence IDDM risk.

Case-control study of IDDM.

Insulin-dependent diabetes mellitus (IDDM) may be caused by a combination of genetic predisposition and environmental insults. However, there are few solid leads concerning human diabetogenic environmental agents. A case-control study was carried out to investigate the possible relationships between IDDM and various biological, chemical, and psychological factors. All 161 cases of IDDM among children aged 0-17 yr occurring in Montreal from 1983 to 1986 were included. The parent of each newly diagnosed diabetic subject was asked to provide the names of two of the child's friends or neighbors who would be age and sex matched to serve as controls. For those unable to do so, matched controls were selected from a hospital emergency room. Parents of cases and controls were interviewed concerning many factors. There was little or no difference between cases and controls with regard to parental smoking habits, exposure to pets, and consumption of meat products high in nitrosamines. In univariate analyses, there was some indication of elevated risk for children who had not been breast-fed, who attended day care or nursery before age 5 yr, who lived in a crowded household at age 3 yr, or who had a history of asthma or eczema, although in multivariate analyses the only variables that had any effect were crowding and day-care attendance. In univariate and multivariate analyses, there was high risk of IDDM among children who had experienced selected stressful life events during the 12 mo preceding onset of IDDM or who had exhibited symptoms of social or psychological dysfunction during that time.(ABSTRACT TRUNCATED AT 250 WORDS)

Pre-HAART HIV burden approximates post-HAART viral levels following interruption of therapy in patients with sustained viral suppression.

OBJECTIVE: To evaluate the relationship between the HIV viral burden in individuals prior to receiving highly-active antiretroviral therapy (HAART) and the viral burden after withdrawal of HAART. DESIGN AND SETTING: Retrospective cohort study at the National Institutes of Health, Bethesda, Maryland, USA. PATIENTS: Fourteen HIV-infected patients who achieved and maintained viral control on HAART who subsequently discontinued HAART. MAIN OUTCOME MEASURES: Pre- and post-HAART viral loads measured from plasma or serum. RESULTS: Patients achieved viral control (< 500 copies/ml) on HAART in a median 28 days (range, 15-490 days; mean, 72 days), maintained viral control for a median 661 days (range, 53-1067 days; mean, 611 days), and subsequently discontinued HAART for a median 49 days (range, 14-196 days; mean, 73 days). The median difference between the pre- and post-HAART viral loads was 0.16 log10 (range, -0.72 to 1.05 log10; mean, 0.19 log10). The median absolute difference between the pre- and post-HAART viral loads was 0.43 log10 (range, 0.06-1.05 log10; mean, 0.46 log10). Nine individuals had post-HAART values higher than pre-HAART values, five had lower values. Median duration between pre- and post-HAART viral load measurements was 1757 days (range, 117-3177 days; mean, 1756 days), or 4.8 years. CONCLUSIONS: After discontinuing HAART, individuals had rebounds in their viral burdens approximating pre-HAART levels, even after a significant lapse of time approaching 5 years. Our data suggest that an intrinsic viral load set-point may exist, and that a single interruption of an effective regimen with viral suppression for almost 2 years does not significantly alter this set-point.

Isolation of HIV-1 from plasma of infected individuals: an analysis of experimental conditions affecting successful virus propagation.

Experimental conditions affecting the successful propagation of HIV-1 from the plasma of seropositive individuals were examined. It was determined that whole blood samples collected with lithium heparin as the anticoagulant, immediate plasma separation, and immediate culturing were best suited for obtaining viable virus from plasma. Virus was isolated by infecting fresh phytohemagglutinin-stimulated normal donor peripheral blood mononuclear cells (PBMCs) with plasma followed by weekly cocultivation with new target cells. The plasma virus isolation rate was the greatest and HIV-1 titers were the highest for those individuals with less than 200 CD4+ cells/mm3 and decreased as the level of CD4+ cells approached normal values. We were able to obtain positive cultures from 29.5% of those patients with CD4+ counts greater than 500/mm3. HIV-1 titers in plasma also correlated with high serum p24 antigen levels when serum was treated with glycine to dissociate antigen-antibody complexes.

Morquio syndrome (MPS IVA) and hypophosphatasia in a Hutterite kindred.

A patient is described who has Morquio syndrome (MPS IVA). He is a member of the Hutterite Brethren and genealogic analysis discloses a high inbreeding coefficient for the proband. The proband's sibship is segregating two autosomal recessive disorders, ie, MPS IVA and infantile hypophosphatasia. Two other families each have one or the other of these diseases but not both. The three families are distantly related.

Predicted changes in the synchrony of larval emergence and budburst under climatic warming.

The impact of climatic warming on the synchrony of insect and plant phenologies was modelled in the case of winter moth (Operophtera brumata) and Sitka spruce (Picea sitchensis) in the Scottish uplands. The emergence of winter moth larvae was predicted with a thermal time requirement model and the budburst of Sitka spruce was predicted from a previously published model (Cannell and Smith 1983) based on winter chilling and thermal time. The date of emergence of winter moth larvae was predicted to occur earlier under climatic warming but the date of budburst of Sitka spruce was not greatly changed, resulting in decreased synchrony between larval emergence and budburst. The general question of how a change of climate might affect phenological synchrony and insect abundance is discussed.

Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH)-syndrome. Ultrastructural changes of mitochondria in cultured dermal fibroblasts of three patients.

Mitochondria of fibroblasts cultured from the skin obtained at biopsy from three patients with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH)-syndrome, one of the autosomal recessive, heritable urea cycle disorders, were studied with appropriate controls ultrastructurally. The patients were two severely retarded 10- and 12-year-old boys, and a 22-year-old sister of the former whose mental status was at the low normal range; she never had motor impairments or seizures. The mitochondria, similar in all three patients, were increased in number, very long, branching and/or "looping," and tortuous. "Spurs" or "buddings" extended from their lateral surfaces and the terminal segments were often bulbous. Other unusual configurations were also present. In addition, giant forms with large diameter contained innumerable closely-packed and parallel cristae which traversed the entire width of these mitochondria; at times they assumed a "whirled" pattern. The mitochondrial matrix was usually of high electron density. These changes were not a feature of fibroblastic mitochondria of controls. Several changes resembled those of hepatic mitochondria in this disorder. All features are interpreted as an attempt at expanding the mitochondrial volume (via structural substratum) to compensate for the metabolic incompetence of these organelles (a block in transmembranous transfer of ornithine from hyaloplasm into mitochondria for conversion to citrulline).

Inflammatory breast carcinoma: comparison of survival of those diagnosed clinically, pathologically, or with both features.

There still remains some controversy as to whether or not there is a survival difference in patients with inflammatory breast carcinoma (IBC) with regard to whether they were diagnosed clinically, pathologically, or with both features. We conducted a retrospective chart review of all the patients diagnosed with IBC who were treated at the Nova Scotia Cancer Treatment and Research foundation between the years of 1990 and 1994, inclusive. Fifty-seven patients' charts were reviewed for recurrence or death up until Feb. 16, 1996. The overall survival of the 57 patients was 32 per cent (confidence interval, 16-48%) and 12 per cent (confidence interval, 0-26%) at 3 and 5 years, respectively. The survival times according to presentation (clinical, pathological, or both) at 3 and 5 years were 31 and 10 per cent for the clinically diagnosed group, 56 per cent at 3 years for the pathologically diagnosed group (5-year survival times could not be calculated), and 34 and 20 per cent for the group diagnosed both clinically and pathologically, respectively. Analysis by the log-rank test revealed that there was no significant difference in survival between these three groups. We conclude that there was no statistically significant difference in survival between those patients who presented clinically, pathologically, or with both features.