Localized Nanoresonator Mode in Plasmonic Microcavities.

Submicron-thick hexagonal boron nitride crystals embedded in noble metals form planar Fabry-Perot half-microcavities. Depositing Au nanoparticles on top of these microcavities forms previously unidentified angle- and polarization-sensitive nanoresonator modes that are tightly laterally confined by the nanoparticle. Comparing dark-field scattering with reflection spectroscopies shows plasmonic and Fabry-Perot-like enhancements magnify subtle interference contributions, which lead to unexpected redshifts in the dark-field spectra, explained by the presence of these new modes.

Cleaning interfaces in layered materials heterostructures.

Heterostructures formed by stacking layered materials require atomically clean interfaces. However, contaminants are usually trapped between the layers, aggregating into randomly located blisters, incompatible with scalable fabrication processes. Here we report a process to remove blisters from fully formed heterostructures. Our method is over an order of magnitude faster than those previously reported and allows multiple interfaces to be cleaned simultaneously. We fabricate blister-free regions of graphene encapsulated in hexagonal boron nitride with an area ~ 5000 µm2, achieving mobilities up to 180,000 cm2 V-1 s-1 at room temperature, and 1.8 × 106 cm2 V-1 s-1 at 9 K. We also assemble heterostructures using graphene intentionally exposed to polymers and solvents. After cleaning, these samples reach similar mobilities. This demonstrates that exposure of graphene to process-related contaminants is compatible with the realization of high mobility samples, paving the way to the development of wafer-scale processes for the integration of layered materials in (opto)electronic devices.

Relative weight at ages 10 and 16 years and risk of endometriosis: a case-control analysis.

BACKGROUND: Although previous epidemiological studies have shown that women with endometriosis are more likely to be thinner and underweight, it is currently not clear whether this is a true characteristic of women who develop endometriosis or a consequence of their disease and its symptoms. The aim of this study was to investigate the relationship between endometriosis and relative weight in childhood and adolescence, prior to diagnosis. METHODS: This case-control study included 268 Australian women with surgically confirmed moderate to severe endometriosis (cases) and 244 women without endometriosis (controls). Relative weight at ages 10 and 16 years, as recalled and classified ('underweight', 'average weight' and 'overweight') separately by the women themselves and their mothers, was analyzed. RESULTS: Women who reported being overweight at 10 years had an increased risk of endometriosis (OR 2.8; 95% CI 1.1-7.5). Mothers' reports and concordant responses among mother-daughter pairs were consistent with this association. There was no clear evidence of an association between relative weight at 16 years and risk of endometriosis. CONCLUSIONS: These data suggest that being overweight during late childhood is associated with the development of endometriosis; however, the results warrant confirmation in larger study populations.

Ten-year outcomes following traumatic brain injury: a population-based cohort.

PRIMARY OBJECTIVE: To quantify the 10 year health service use (HSU) and mortality outcomes for people with a traumatic brain injury (TBI). RESEARCH DESIGN: A population-based matched cohort study using linked administrative data from Manitoba, Canada (Manitoba Injury Outcome Study). METHODS AND PROCEDURES: An inception cohort (1988-1991) of hospitalized cases with TBI aged 18-64 years (n = 1290) was identified and matched to a non-injured comparison group (n = 1290). Survival analysis, Negative binomial and Poisson regression were used to quantify associations between injury and HSU/mortality outcomes for 10 years following the TBI event. MAIN OUTCOME AND RESULTS: The majority of deaths (47.2%) occurred in the first 60 days following injury. Excluding the first 60 days, the adjusted 10 year mortality remained elevated (mortality rate ratio = 1.48, 95% CI = 1.02-2.15). After adjusting for demographic characteristics and pre-existing health status, the TBI cohort had more post-injury hospitalizations (rate ratio (RR) = 1.54, 95% CI = 1.39-1.71), greater cumulative lengths of stay (RR = 5.14, 95% CI = 3.29-8.02) and a greater post-injury physician claims rate (RR = 1.44, 95% CI = 1.35-1.53) than the non-injured cohort. CONCLUSIONS: People who sustain a TBI and survive the initial acute phase of care experience substantially increased long-term morbidity compared to the general population, regardless of the level of injury severity.

Moderate alcohol consumption contributes to women's well-being through the menopausal transition.

OBJECTIVES: To examine the association of alcohol consumption with well-being in mid-aged Australian women, taking into account other lifestyle factors. METHODS: A prospective, observational study was carried out among 438 urban Australian women aged 45-55 years at baseline. They were assessed annually for 8 years using a questionnaire on health and lifestyle, including self-ratings of well-being and daily 'hassles'. Statistical analyses were performed using cluster and repeated measures analyses. RESULTS: About 80% of the women had consumed alcohol in the week preceding the interview. Alcohol intake was weakly associated with well-being overall (p = 0.094). Women who consumed alcohol at moderate levels had higher well-being scores than non-drinkers or heavy drinkers, however, provided they were also non-smokers and exercised weekly or more (p for interaction = 0.023) (21% of all study participants). Everyday symptoms and stresses had a negative impact on well-being (all p values < 0.001). CONCLUSIONS: Among women undergoing menopausal transition, well-being is positively associated with moderate alcohol consumption along with other lifestyle factors in a synergistic fashion, rather than any individual factor having a dominant or an independent effect.

Long-term mortality following injury in working-age adults: a systematic review.

Priorities for prevention activities and planning for services depend on comprehensive knowledge of the distribution of the injury-related burden in the community. The aim of this systematic review was to quantify the effect of being injured, compared with not being injured, on long-term mortality in working age adults. Cohort studies were selected that were population-based, measured mortality post-discharge from inpatient treatment, included a non-injured comparison group and related to working-age adults. Data synthesis was in tabular and text form with a meta-analysis not being possible because of the heterogeneity between studies. Eleven studies met the inclusion criteria. All studies found an overall positive association between injury and increased mortality. While the greatest excess mortality was evident during the initial period post-injury, increased mortality was shown in some studies to persist for up to 40 years after injury. Due to the limited number of injury types studied and heterogeneity between studies, there is insufficient published evidence on which to calculate population estimates of long-term mortality, where injury is a component cause. The review does suggest there is considerable excess mortality following injury that is not accounted for in current methods of quantifying injury burden, and is not used to assess quality and effectiveness of trauma care.

Ten-year health service use outcomes in a population-based cohort of 21,000 injured adults: the Manitoba injury outcome study.

OBJECTIVE: To quantify long-term health service use (HSU) following non-fatal injury in adults. METHODS: A retrospective, population-based, matched cohort study identified an inception cohort (1988-91) of injured people who had been hospitalized (ICD-9-CM 800-995) aged 18-64 years (n = 21 032) and a matched non-injured comparison group (n = 21 032) from linked administrative data from Manitoba, Canada. HSU data (on hospitalizations, cumulative length of stay, physician claims and placements in extended care services) were obtained for the 12 months before and 10 years after the injury. Negative binomial and Poisson regressions were used to quantify associations between injury and long-term HSU. FINDINGS: Statistically significant differences in the rates of HSU existed between the injured and non-injured cohorts for the pre-injury year and every year of the follow-up period. After controlling for pre-injury HSU, the attributable risk percentage indicated that 38.7% of all post-injury hospitalizations (n = 25 183), 68.9% of all years spent in hospital (n = 1031), 21.9% of physician claims (n = 269 318) and 77.1% of the care home placements (n = 189) in the injured cohort could be attributed to being injured. CONCLUSION: Many people who survive the initial period following injury, face long periods of inpatient care (and frequent readmissions), high levels of contact with physicians and an increased risk of premature placement in institutional care. Population estimates of the burden of injury could be refined by including long-term non-fatal health consequences and controlling for the effect of pre-injury comorbidity.

Medication management at home: medication risk factor prevalence and inter-relationships.

BACKGROUND AND OBJECTIVE: Patients can have medication-related risk factors associated with poor health outcomes that become evident through visiting them in their homes. These medication-related risk factors may not be apparent in pharmacy and general practitioner (GP) records. The aim was to determine the prevalence and inter-relationships of medication-related risk factors for poor patient health outcomes identifiable through 'in-home' observations. METHODS: The design was a cross-sectional study of 204 general practice patients living in their own homes and at risk of medication-related poor health outcomes. Medication-related risk factors were identified in the patients' homes by community pharmacists and GPs. RESULTS AND DISCUSSION: The prevalence of risk factors varied from 8.3% (multiple medication storage locations) to 55.9% (confused by generic and trade names). There were many relationships observed between the medication-related risk factors, with expired medication having the most relationships with other risk factors followed by therapeutic duplication and poor adherence (9, 6 and 6 relationships respectively). CONCLUSION: Visiting patients' homes may identify medication-related risk factors not otherwise apparent through patient visits to the health practitioner when medications may be brought for review (i.e. 'brown bag' reviews).

The properties of the International Classification of the External Cause of Injury when used as an instrument for injury prevention research.

OBJECTIVE: To demonstrate properties of the International Classification of the External Cause of Injury (ICECI) as a tool for use in injury prevention research. METHODS: The Childhood Injury Prevention Study (CHIPS) is a prospective longitudinal follow up study of a cohort of 871 children 5-12 years of age, with a nested case crossover component. The ICECI is the latest tool in the International Classification of Diseases (ICD) family and has been designed to improve the precision of coding injury events. The details of all injury events recorded in the study, as well as all measured injury related exposures, were coded using the ICECI. This paper reports a substudy on the utility and practicability of using the ICECI in the CHIPS to record exposures. Interrater reliability was quantified for a sample of injured participants using the Kappa statistic to measure concordance between codes independently coded by two research staff. RESULTS: There were 767 diaries collected at baseline and event details from 563 injuries and exposure details from injury crossover periods. There were no event, location, or activity details which could not be coded using the ICECI. Kappa statistics for concordance between raters within each of the dimensions ranged from 0.31 to 0.93 for the injury events and 0.94 and 0.97 for activity and location in the control periods. DISCUSSION: This study represents the first detailed account of the properties of the ICECI revealed by its use in a primary analytic epidemiological study of injury prevention. The results of this study provide considerable support for the ICECI and its further use.

Long term health outcomes after injury in working age adults: a systematic review.

BACKGROUND: Estimating the contribution of non-fatal injury outcomes remains a considerable challenge and is one of the most difficult components of burden of disease analysis. The aim of this systematic review was to quantify the effect of being injured compared with not being injured on morbidity and health service use (HSU) in working age adults. METHODS: Studies were selected that were population based, had long term health outcomes measured, included a non-injured comparison group, and related to working age adults. Meta-analysis was not attempted because of the heterogeneity between studies. RESULTS: Nine studies met the inclusion criteria. In general, studies found an overall positive association between injury and increased HSU, exceeding that of the general population, which in some studies persisted for up to 50 years after injury. Disease outcome studies after injury were less consistent, with null findings reported. CONCLUSION: Because of the limited injury types studied and heterogeneity between study outcome measures and follow up, there is insufficient published evidence on which to calculate population estimates of long term morbidity, where injury is a component cause. However, the review does suggest injured people have an increased risk of long term HSU that is not accounted for in current methods of quantifying injury burden.

Non-response to antiviral therapy is associated with obesity and increased hepatic expression of suppressor of cytokine signalling 3 (SOCS-3) in patients with chronic hepatitis C, viral genotype 1.

BACKGROUND: Interferon alpha (IFN-alpha) activated cellular signalling is negatively regulated by inhibitory factors, including the suppressor of cytokine signalling (SOCS) family. The effects of host factors such as obesity on hepatic expression of these inhibitory factors in subjects with chronic hepatitis C virus (HCV) are unknown. OBJECTIVES: To assess the independent effects of obesity, insulin resistance, and steatosis on response to IFN-alpha therapy and to determine hepatic expression of factors inhibiting IFN-alpha signalling in obese and non-obese subjects with chronic HCV. METHODS: A total of 145 subjects were analysed to determine host factors associated with non-response to antiviral therapy. Treatment comprised IFN-alpha or peginterferon alpha, either alone or in combination with ribavirin. In a separate cohort of 73 patients, real time-polymerase chain reaction was performed to analyse hepatic mRNA expression. Immunohistochemistry for SOCS-3 was performed on liver biopsy samples from 38 patients with viral genotype 1 who had received antiviral treatment. RESULTS: Non-response (NR) to treatment occurred in 55% of patients with HCV genotypes 1 or 4 and 22% with genotypes 2 or 3. Factors independently associated with NR were viral genotype 1/4 (p < 0.001), cirrhosis on pretreatment biopsy (p = 0.025), and body mass index > or = 30 kg/m2 (p = 0.010). Obese subjects with viral genotype 1 had increased hepatic mRNA expression of phosphoenolpyruvate carboxy kinase (p = 0.01) and SOCS-3 (p = 0.047), in comparison with lean subjects. Following multivariate analysis, SOCS-3 mRNA expression remained independently associated with obesity (p = 0.023). SOCS-3 immunoreactivity was significantly increased in obesity (p = 0.013) and in non-responders compared with responders (p = 0.014). CONCLUSIONS: In patients with chronic HCV viral genotype 1, increased expression of factors that inhibit interferon signalling may be one mechanism by which obesity reduces the biological response to IFN-alpha.

Long-term mortality following trauma: 10 year follow-up in a population-based sample of injured adults.

BACKGROUND: The aim of the study was to quantify trauma-related mortality in injured adults over 10 years postinjury. METHODS: A population-based matched cohort study used linked administrative data from Manitoba, Canada, to identify an inception cohort (1988-1991) of hospitalized trauma cases (ICD-9-CM 800-959.9) aged 18-64 years (n = 18,210) and a matched noninjured comparison group (n = 18,210). Mortality outcomes were obtained by linking the two cohorts with the Manitoba Population Registry for a period of 10 years postinjury. RESULTS: The adjusted all-cause mortality rate ratio (MRR) was 7.29 (95% CI 4.53-11.74) for the 60 days immediately postinjury. The MRRs ranged between 1.17 and 2.41 for the remainder of the 10 year follow-up period. The index injury was estimated to be responsible for 41% of all recorded deaths in the injured cohort. CONCLUSIONS: Estimates of the total mortality burden, based on the early inpatient period alone, substantially underestimates the true burden from injury.

A combination of genetic polymorphisms increases the risk of progressive disease in chronic hepatitis C.

BACKGROUND: There is increasing interest in the influence of host genetic factors on hepatic fibrosis, and whether genetic markers can reliably identify subjects at risk of developing severe disease. We hypothesised that hepatitis C virus (HCV) infected subjects with progressive fibrosis, classified using strict criteria based on histology at biopsy in addition to disease duration would be more likely to inherit several genetic polymorphisms associated with disease progression compared with subjects with a low rate of disease progression. METHODS: We examined polymorphisms in eight genes that have been reported to have an association with hepatic fibrosis. RESULTS: Associations between polymorphisms in six genes and more rapidly progressing fibrosis were observed, with individual adjusted odds ratios ranging from 2.1 to 4.5. The relationship between rapidly progressing fibrosis and possession of > or =3, > or =4, or > or =5 progression associated alleles was determined and the adjusted odds ratios increased with increasing number of progression associated alleles (9.1, 15.5, and 24.1, respectively). Using logistic regression analysis, a predictive equation was developed and tested using a second cohort of patients with rapidly progressing fibrosis. The predictive equation correctly classified 80% of patients in this second cohort. CONCLUSIONS: This approach may allow determination of a genetic profile predictive of rapid disease progression in HCV and identify patients warranting more aggressive therapeutic management.

Beating the barriers: recruitment of people with intellectual disability to participate in research.

BACKGROUND: The health status of people with intellectual disability (ID) is poor, yet very little research has been done on their health needs. There are several barriers to performing this research. The aim of our research was to examine the significant barriers encountered in recruiting adults with ID to participate in research. METHODS: Our project was a randomized controlled trial aiming to improve health advocacy of people with ID. We approached many organizations to recruit participants and kept records of our results. Recruitment was very low for the first 4 months. Then we adopted two new recruitment strategies--in-service telephone recruitment and meetings with prospective participants. We then monitored the subsequent recruitment rates. We also questioned participants about the difficulties they encountered when considering recruitment. RESULTS: Initial recruitment of participants yielded less than one-third of the expected number. Additional strategies implemented were partially successful. Significant barriers to recruitment included several sectoral issues and the challenges arising from the research process. CONCLUSIONS: While this population is a difficult one to reach for research, attempts to do so should not be abandoned, because the potential health benefits for this underserved group far outweigh the recruitment barriers experienced.

Indicators of injury burden: which types are the most important?

Injury indicators are used for monitoring the impact of injury prevention initiatives on the population burden of injury. The object of the present study was to identify the types of injury responsible for the major component of the population health burden of injury in a large cohort in Manitoba, Canada. Injury cases (ICD-9-CM 800-995) aged 18-64 years were identified from all Manitoba hospital data between 1988 and 1991. Morbidity data were obtained from hospital discharge abstracts 12 months prior to date of injury and for 12 months post-injury. Outcomes for individuals were calculated as the difference pre- and post-injury in hospital inpatient days. Death outcomes in the 12 months post-injury were obtained by linking the cohort with the population registry. Summed outcomes across the population were stratified into injury types based on the International Code of Diseases (ICD) code of the index injury. Outcomes were also stratified by injury severity score categories where the injury severity score was obtained using ICDMAP-90. When ranked by contribution to the cohort's cumulative hospital inpatient days in the 12 months post-injury, the six most common ICD subchapter groups accounted for 65% of the total inpatient days. These six injury types also accounted for 62% of the total number of deaths in this cohort in 12 months after injury. The suggested injury types to use as indicators of burden include fracture of the lower limb, fracture of the head and neck, poisonings, intracranial injury, fracture of the upper limb, and fracture of skull.

How well do anatomical-based injury severity scores predict health service use in the 12 months after injury?

There is an acknowledged need for valid and reliable injury scores, suitable for use at the population level, which can accurately predict the long-term outcome of injury. The objective was to quantify the extent to which the abbreviated injury severity score (AIS) and the functional capacity index score (FCI) predict use of health services in the 12 months following an injury event. A cohort of injured people (ICD-9-CM 800-995) aged 18 - 64 years was identified from Manitoba hospital discharge abstracts from January 1988 to December 1991. For each member of the cohort whose injuries could be mapped to an abbreviated injury scale unique identifier, a maximum AIS (maxAIS) and a maximum FCI (maxFCI) were obtained. The cohort was linked with hospital discharge abstracts, physicians' claims and deaths from the population registry for the 12 months following injury. Negative binomial regression was used to model the relationships between the severity scores and the three outcome measures, while controlling for potential confounding variables. In total, 20 677 (97%) eligible cases were identified, of which 16 834 (81%) could be assigned a maxAIS and 15 823 (77%) a maxFCI. MaxAIS and maxFCI were significantly associated with total days in hospital following injury, but explained little of the variation in any of the health service use outcome variables (maxAIS, partial pseudo r2 ranging from < 0.001 to 0.041; and maxFCI, partial pseudo r2 ranging from < 0.001 to 0.018). It was concluded that anatomical damage is only partly responsible for long-term injury outcome. Additional variables would need to be included in predictive models of health outcomes of injury before these models could be reliable.

Modulation of human Valpha24(+)Vbeta11(+) NKT cells by age, malignancy and conventional anticancer therapies.

Immunotherapy strategies aimed at increasing human Valpha24(+)Vbeta11(+) natural killer T (NKT) cell numbers are currently a major focus. To provide further information towards the goal of NKT cell-based immunotherapy, we assessed the effects of age, cancer status and prior anticancer treatment on NKT cell numbers and their expansion capacity following alpha-galactosylceramide (alpha-GalCer) stimulation. The percentage and absolute number of peripheral blood NKT cells was assessed in 40 healthy donors and 109 solid cancer patients (colorectal (n=33), breast (n=10), melanoma (n=17), lung (n=8), renal cell carcinoma (n=10), other cancers (n=31)). Responsiveness to alpha-GalCer stimulation was also assessed in 28 of the cancer patients and 37 of the healthy donors. Natural killer T cell numbers were significantly reduced in melanoma and breast cancer patients. While NKT numbers decreased with age in healthy donors, NKT cells were decreased in these cancer subgroups despite age and sex adjustments. Prior radiation treatment was shown to contribute to the observed reduction in melanoma patients. Although cancer patient NKT cells were significantly less responsive to alpha-GalCer stimulation, they remained capable of substantial expansion. Natural killer T cells are therefore modulated by age, malignancy and prior anticancer treatment; however, cancer patient NKT cells remain capable of responding to alpha-GalCer-based immenotherapies.

Comparison of the effects of two different types of calcium supplementation on markers of bone metabolism in a postmenopausal osteopenic population with low calcium intake: a double-blind placebo-controlled trial.

OBJECTIVE: To investigate calcium supplements in postmenopausal women. Calcium supplements in postmenopausal women with a low calcium intake have been shown to prevent osteoporotic vertebral fracture, but calcium is variably absorbed and often poorly tolerated, which may limit effectiveness. METHODS: The study compared the efficacy and tolerability of 500 mg/day of calcium in the form of ossein-hydroxyapatite (OHC) versus 500 mg/day of tricalcium phosphate (TCP) and placebo in the prevention of postmenopausal bone loss. This was a prospective randomized study enrolling 153 postmenopausal osteopenic women. Serum and urine markers of bone turnover were collected at 3 and 6 months. Bone density measurement was performed at baseline and 6 months in all participants, and at 12 months in women taking OHC. RESULTS: At 3 and 6 months, both TCP and OHC decreased serum markers of bone formation significantly, compared with placebo. At 6 months, TCP and OHC decreased osteocalcin by 9.9% and 12.3%, respectively; the aminoterminal propeptide of type I procollagen (PINP) was decreased by 5.3% and 6.3%, respectively; bone-specific alkaline phosphatase was decreased by 4.3% and 6.7%, respectively, compared with baseline. The effects on bone resorption markers or on bone mineral density did not reach statistical significance, although OHC increased bone density by 0.8% at the spine at 12 months. Both forms of calcium were well tolerated and did not differ from placebo in terms of side-effects. CONCLUSIONS: While both OHC and TCP were well tolerated and significantly reduced bone turnover markers, the effect of ossein-hydroxyapatite seems slightly superior to that of tricalcium phosphate.

CCR5-Delta32 mutation is strongly associated with primary sclerosing cholangitis.

CCR5 plays a key role in the distribution of CD45RO+ T cells and contributes to generation of a T helper 1 immune response. CCR5-Delta32 is a 32-bp deletion associated with significant reduction in cell surface expression of the receptor. We investigated the role of CCR5-Delta32 on susceptibility to ulcerative colitis (UC), Crohn's disease (CD) and primary sclerosing cholangitis (PSC). Genotype and allelic association analyses were performed in 162 patients with UC, 131 with CD, 71 with PSC and 419 matched controls. There was a significant difference in CCR5 genotype (OR 2.27, P=0.003) between patients with sclerosing cholangitis and controls. Similarly, CCR5-Delta32 allele frequency was significantly higher in sclerosing cholangitis (17.6%) compared to controls (9.9%, OR 2.47, P=0.007) and inflammatory bowel disease patients without sclerosing cholangitis (11.3%, OR 1.9, P=0.027). There were no significant differences in CCR5 genotype or allele frequency between those with either UC or CD and controls. Genotypes with the CCR5-Delta32 variant were increased in patients with severe liver disease defined by portal hypertension and/or transplantation (45%) compared to those with mild liver disease (21%, OR 3.17, P=0.03). The CCR5-Delta32 mutation may influence disease susceptibility and severity in patients with PSC.