AbstractObjectiveTo estimate the effectiveness of mRNA covid-19 vaccines against symptomatic infection and severe outcomes (hospital admission or death).DesignTest negative design ...study.SettingOntario, Canada between 14 December 2020 and 19 April 2021.Participants324 033 community dwelling people aged ≥16 years who had symptoms of covid-19 and were tested for SARS-CoV-2.InterventionsBNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine.Main outcome measuresLaboratory confirmed SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) and hospital admissions and deaths associated with SARS-CoV-2 infection. Multivariable logistic regression was adjusted for personal and clinical characteristics associated with SARS-CoV-2 and vaccine receipt to estimate vaccine effectiveness against symptomatic infection and severe outcomes.ResultsOf 324 033 people with symptoms, 53 270 (16.4%) were positive for SARS-CoV-2 and 21 272 (6.6%) received at least one dose of vaccine. Among participants who tested positive, 2479 (4.7%) were admitted to hospital or died. Vaccine effectiveness against symptomatic infection observed ≥14 days after one dose was 60% (95% confidence interval 57% to 64%), increasing from 48% (41% to 54%) at 14-20 days after one dose to 71% (63% to 78%) at 35-41 days. Vaccine effectiveness observed ≥7 days after two doses was 91% (89% to 93%). Vaccine effectiveness against hospital admission or death observed ≥14 days after one dose was 70% (60% to 77%), increasing from 62% (44% to 75%) at 14-20 days to 91% (73% to 97%) at ≥35 days, whereas vaccine effectiveness observed ≥7 days after two doses was 98% (88% to 100%). For adults aged ≥70 years, vaccine effectiveness estimates were observed to be lower for intervals shortly after one dose but were comparable to those for younger people for all intervals after 28 days. After two doses, high vaccine effectiveness was observed against variants with the E484K mutation.ConclusionsTwo doses of mRNA covid-19 vaccines were observed to be highly effective against symptomatic infection and severe outcomes. Vaccine effectiveness of one dose was observed to be lower, particularly for older adults shortly after the first dose.
Singlet fission is the spin-allowed conversion of a spin-singlet exciton into a pair of spin-triplet excitons residing on neighbouring molecules. To rationalize this phenomenon, a multiexcitonic ...spin-zero triplet-pair state has been hypothesized as an intermediate in singlet fission. However, the nature of the intermediate states and the underlying mechanism of ultrafast fission have not been elucidated experimentally. Here, we study a series of pentacene derivatives using ultrafast two-dimensional electronic spectroscopy and unravel the origin of the states involved in fission. Our data reveal the crucial role of vibrational degrees of freedom coupled to electronic excitations that facilitate the mixing of multiexcitonic states with singlet excitons. The resulting manifold of vibronic states drives sub-100 fs fission with unity efficiency. Our results provide a framework for understanding singlet fission and show how the formation of vibronic manifolds with a high density of states facilitates fast and efficient electronic processes in molecular systems.
Many scholars assert that Indigenous peoples across the globe suffer a disproportionate burden of mental illness. Research indicates that colonialism and its associated processes are important ...determinants of Indigenous peoples’ health internationally. In Canada, despite an abundance of health research documenting inequalities in morbidity and mortality rates for Indigenous peoples, relatively little research has focused on mental health. This paper provides a critical scoping review of the literature related to Indigenous mental health in Canada. We searched eleven databases and two Indigenous health-focused journals for research related to mental health, Indigenous peoples, and Canada, for the years 2006–2016. Over two hundred papers are included in the review and coded according to research theme, population group, and geography. Results demonstrate that the literature is overwhelmingly concerned with issues related to colonialism in mental health services and the prevalence and causes of mental illness among Indigenous peoples in Canada, but with several significant gaps. Mental health research related to Indigenous peoples in Canada overemphasizes suicide and problematic substance use; a more critical use of the concepts of colonialism and historical trauma is advised; and several population groups are underrepresented in research, including Métis peoples and urban or off-reserve Indigenous peoples. The findings are useful in an international context by providing a starting point for discussions, dialogue, and further study regarding mental health research for Indigenous peoples around the world.
•Most research addresses colonialism; more nuanced approaches are recommended.•Overemphasis of substance use problems and suicide can have negative implications.•Mental health services developed by Indigenous communities are most effective.•Inuit are overrepresented in research; Métis are drastically underrepresented.•Urban and off-reserve Indigenous populations are dramatically underrepresented.
AbstractObjectivesTo estimate the marginal effectiveness of a fourth versus third dose and the vaccine effectiveness of mRNA covid-19 vaccines BNT162b2 and mRNA-1273 against any infection, ...symptomatic infection, and severe outcomes (hospital admission or death) related to the omicron variant.DesignTest negative design.SettingLong term care facilities in Ontario, Canada, 30 December 2021 to 27 April 2022.ParticipantsAfter exclusions, 61 344 residents aged 60 years or older across 626 long term care facilities in Ontario, Canada who were tested for SARS-CoV-2 were included.Main outcome measuresLaboratory confirmed omicron SARS-CoV-2 infection (any and symptomatic) by reverse transcription polymerase chain reaction (RT-PCR), and hospital admission or death. Multivariable logistic regression was used to estimate marginal effectiveness (four versus three doses) and vaccine effectiveness (two, three, or four doses versus no doses) while adjusting for personal characteristics, comorbidities, week of test, and previous positive SARS-CoV-2 test result more than 90 days previously.Results13 654 residents who tested positive for omicron SARS-CoV-2 infection and 205 862 test negative controls were included. The marginal effectiveness of a fourth dose (95% of vaccine recipients received mRNA-1273 as the fourth dose) seven days or more after vaccination versus a third dose received 84 or more days previously was 19% (95% confidence interval 12% to 26%) against infection, 31% (20% to 41%) against symptomatic infection, and 40% (24% to 52%) against severe outcomes. Vaccine effectiveness in vaccine recipients (compared with unvaccinated) increased with each additional dose, and for a fourth dose was 49% (95% confidence interval 43% to 54%) against infection, 69% (61% to 76%) against symptomatic infection, and 86% (81% to 90%) against severe outcomes.ConclusionsThe findings suggest that compared with a third dose of mRNA covid-19 vaccine, a fourth dose improved protection against infection, symptomatic infection, and severe outcomes among long term care residents during an omicron dominant period. A fourth vaccine dose was associated with strong protection against severe outcomes in vaccinated residents compared with unvaccinated residents, although the duration of protection remains unknown.
Almost 1.7 million people in the settler colonial nation of Canada identify as Indigenous. Approximately 52 per cent of Indigenous peoples in Canada live in urban areas. In spite of high rates of ...urbanization, urban Indigenous peoples are overlooked in health care policy and services. Because of this, although health care services are more plentiful in cities as compared to rural areas, Indigenous people still report significant barriers to health care access in urban settings. This qualitative study, undertaken in Prince George, Canada, examines perceived barriers to health care access for urban Indigenous people in light of how colonialism impacts Indigenous peoples in their everyday lives. The three most frequently reported barriers to health care access on the part of the 65 participating health care providers and Indigenous clients of health care services are: substandard quality of care; long wait times; and experiences of racism and discrimination. These barriers, some of which are common complaints among the general population in Canada, are interpreted by Indigenous clients in unique ways rooted in experiences of discrimination and exclusion that stem from the settler colonial context of the nation. Through the lenses of cultural safety and ethical space – frameworks developed by international Indigenous scholars in efforts to better understand and operationalize relationships between Indigenous and non-Indigenous individuals and societies in the context of settler colonialism – this study offers an understanding of these barriers in light of the specific ways that colonialism intrudes into Indigenous clients’ access to care on an everyday basis.
•Urban Indigenous peoples are overlooked in health care policy and practice.•Participants include 15 health care providers and 50 Indigenous clients.•Prince George provides a unique, small, northern urban setting for this study.•Perceived racism and discrimination are major barriers to health care access.•Cultural safety and ethical space help to understand how colonialism impacts access.
IMPORTANCE: There is limited comparative epidemiological evidence on outcomes associated with COVID-19 vaccination during pregnancy; monitoring pregnancy outcomes in large populations is required. ...OBJECTIVE: To evaluate peripartum outcomes following COVID-19 vaccination during pregnancy. DESIGN, SETTING, AND PARTICIPANTS: Population-based retrospective cohort study in Ontario, Canada, using a birth registry linked with the provincial COVID-19 immunization database. All births between December 14, 2020, and September 30, 2021, were included. EXPOSURES: COVID-19 vaccination during pregnancy, COVID-19 vaccination after pregnancy, and no vaccination. MAIN OUTCOMES AND MEASURES: Postpartum hemorrhage, chorioamnionitis, cesarean delivery (overall and emergency cesarean delivery), admission to neonatal intensive care unit (NICU), and low newborn 5-minute Apgar score (<7). Linear and robust Poisson regression was used to generate adjusted risk differences (aRDs) and risk ratios (aRRs), respectively, comparing cumulative incidence of outcomes in those who received COVID-19 vaccination during pregnancy with those vaccinated after pregnancy and those with no record of COVID-19 vaccination at any point. Inverse probability of treatment weights were used to adjust for confounding. RESULTS: Among 97 590 individuals (mean SD age, 31.9 4.9 years), 22 660 (23%) received at least 1 dose of COVID-19 vaccine during pregnancy (63.6% received dose 1 in the third trimester; 99.8% received an mRNA vaccine). Comparing those vaccinated during vs after pregnancy (n = 44 815), there were no significantly increased risks of postpartum hemorrhage (incidence: 3.0% vs 3.0%; aRD, −0.28 per 100 individuals 95% CI, −0.59 to 0.03; aRR, 0.91 95% CI, 0.82-1.02), chorioamnionitis (0.5% vs 0.5%; aRD, −0.04 per 100 individuals 95% CI, −0.17 to 0.09; aRR, 0.92 95% CI, 0.70-1.21), cesarean delivery (30.8% vs 32.2%; aRD, −2.73 per 100 individuals 95% CI, −3.59 to −1.88; aRR, 0.92 95% CI, 0.89-0.95), NICU admission (11.0% vs 13.3%; aRD, −1.89 per 100 newborns 95% CI, −2.49 to −1.30; aRR, 0.85 95% CI, 0.80-0.90), or low Apgar score (1.8% vs 2.0%; aRD, −0.31 per 100 newborns 95% CI, −0.56 to −0.06; aRR, 0.84 95% CI, 0.73-0.97). Findings were qualitatively similar when compared with individuals who did not receive COVID-19 vaccination at any point (n = 30 115). CONCLUSIONS AND RELEVANCE: In this population-based cohort study in Ontario, Canada, COVID-19 vaccination during pregnancy, compared with vaccination after pregnancy and with no vaccination, was not significantly associated with increased risk of adverse peripartum outcomes. Study interpretation should consider that the vaccinations received during pregnancy were primarily mRNA vaccines administered in the second and third trimester.
Increased rates of myocarditis or pericarditis following receipt of COVID-19 mRNA vaccines have been observed. However, few available data are associated with differences in rates of myocarditis or ...pericarditis specific to vaccine products, which may have important implications for vaccination programs.
To estimate rates of reported myocarditis or pericarditis following receipt of a COVID-19 mRNA vaccine by product, age, sex, dose number, and interdose interval.
This population-based cohort study was conducted in Ontario, Canada (population: 14.7 million) from December 2020 to September 2021 and used data from Ontario's COVID-19 vaccine registry and passive vaccine-safety surveillance system. All individuals in Ontario, Canada, who received at least 1 dose of COVID-19 mRNA vaccine between December 14, 2020, and September 4, 2021, and had a reported episode of myocarditis or pericarditis following receipt of the COVID-19 vaccine during this period were included. We obtained information on all vaccine doses administered in the province to calculate reported rates of myocarditis or pericarditis.
Receipt of a COVID-19 mRNA vaccine (mRNA-1273 Moderna Spikevax or BNT162b2 Pfizer-BioNTech Comirnaty).
All reports of myocarditis or pericarditis meeting levels 1 to 3 of the Brighton Collaboration case definitions were included. Rates and 95% CIs of reported cases of myocarditis or pericarditis per 1 000 000 mRNA vaccine doses administered were calculated by age, sex, dose number, vaccine product, and interdose interval.
Among 19 740 741 doses of mRNA vaccines administered, there were 297 reports of myocarditis or pericarditis meeting the inclusion criteria; 228 (76.8%) occurred in male individuals, and the median age of individuals with a reported event was 24 years (range, 12-81 years). Of the reported cases, 207 (69.7%) occurred following the second dose of the COVID-19 mRNA vaccine. When restricted to individuals who received their second dose during the period of enhanced passive surveillance (on or after June 1, 2021), the highest rate of myocarditis or pericarditis was observed in male individuals aged 18 to 24 years following mRNA-1273 as the second dose (299.5 cases per 1 000 000 doses; 95% CI, 171.2-486.4 cases per 1 000 000 doses); the rate following BNT162b2 as the second dose was 59.2 cases per 1 000 000 doses (95% CI, 19.2-138.1 cases per 1 000 000 doses). Overall rates for both vaccine products were significantly higher when the interdose interval was 30 or fewer days (BNT162b2: 52.1 cases per 1 000 000 doses 95% CI, 31.8-80.5 cases per 1 000 000 doses; mRNA-1273: 83.9 cases per 1 000 000 doses 95% CI, 47.0-138.4 cases per 1 000 000 doses) compared with 56 or more days (BNT162b2: 9.6 cases per 1 000 000 doses 95% CI, 6.5-13.6 cases per 1 000 000 doses; mRNA-1273: 16.2 cases per 1 000 000 doses 95% CI, 10.2-24.6 cases per 1 000 000 doses).
The findings of this population-based cohort study of Ontario adolescents and adults with myocarditis or pericarditis following mRNA COVID-19 vaccination suggest that vaccine products and interdose intervals, in addition to age and sex, may be associated with the risk of myocarditis or pericarditis after receipt of these vaccines. Vaccination program strategies, such as age-based product considerations and longer interdose intervals, may reduce the risk of myocarditis or pericarditis following receipt of mRNA vaccines.
Germline mutations in BRCA1/2 predispose individuals to breast cancer (termed germline-mutated BRCA1/2 breast cancer, gBRCA-BC) by impairing homologous recombination (HR) and causing genomic ...instability. HR also repairs DNA lesions caused by platinum agents and PARP inhibitors. Triple-negative breast cancers (TNBCs) harbor subpopulations with BRCA1/2 mutations, hypothesized to be especially platinum-sensitive. Cancers in putative 'BRCAness' subgroups-tumors with BRCA1 methylation; low levels of BRCA1 mRNA (BRCA1 mRNA-low); or mutational signatures for HR deficiency and those with basal phenotypes-may also be sensitive to platinum. We assessed the efficacy of carboplatin and another mechanistically distinct therapy, docetaxel, in a phase 3 trial in subjects with unselected advanced TNBC. A prespecified protocol enabled biomarker-treatment interaction analyses in gBRCA-BC and BRCAness subgroups. The primary endpoint was objective response rate (ORR). In the unselected population (376 subjects; 188 carboplatin, 188 docetaxel), carboplatin was not more active than docetaxel (ORR, 31.4% versus 34.0%, respectively; P = 0.66). In contrast, in subjects with gBRCA-BC, carboplatin had double the ORR of docetaxel (68% versus 33%, respectively; biomarker, treatment interaction P = 0.01). Such benefit was not observed for subjects with BRCA1 methylation, BRCA1 mRNA-low tumors or a high score in a Myriad HRD assay. Significant interaction between treatment and the basal-like subtype was driven by high docetaxel response in the nonbasal subgroup. We conclude that patients with advanced TNBC benefit from characterization of BRCA1/2 mutations, but not BRCA1 methylation or Myriad HRD analyses, to inform choices on platinum-based chemotherapy. Additionally, gene expression analysis of basal-like cancers may also influence treatment selection.
Ontario, Canada introduced a publicly-funded 13-valent pneumococcal conjugate vaccine (PCV13) for infants in 2010, replacing the 10-valent (PCV10, 2009-2010) and the 7-valent (PCV7, 2005-2009) ...conjugate vaccine programs; a 23-valent pneumococcal polysaccharide vaccine (PPV23) has been available for older adults since 1996. We examined the epidemiology and serotype distribution of invasive pneumococcal disease (IPD) in Ontario in the context of provincial immunization programs.
We included confirmed IPD cases reported in Ontario between 2007 and 2017. We grouped serotypes according to Ontario's current immunization program (PCV13, PPV23, and non-vaccine-preventable) and calculated incidence rates (per 100,000 population) using population data.
Between 2007 and 2017, annual incidence of IPD in Ontario ranged between 7.3 and 9.7/100,000 per year. Measures of illness severity were high throughout the period of surveillance. After PCV13 program implementation in 2010, incidence due to PCV13 serotypes decreased significantly across all age groups, with the greatest reductions in children <5 years and adults ≥65 years. Conversely, incidence due to PPV23 unique serotypes increased significantly between 2007 and 2017, with the greatest increases observed in adults 50-64 years (1.4 to 3.5/100,000) and ≥65 years (2.3 to 7.2/100,000). Similar increases were observed in incidence due to non-vaccine-preventable serotypes among all age groups, except infants <1 year. Within specific serotypes, incidence due to serotypes 3 (0.42 to 0.98/100,000) and 22F (0.31 to 0.72/100,000) increased significantly between 2007 and 2017, while incidence due to serotypes 19A and 7F decreased significantly during the PCV13 period (2010-2017).
Eight years after PCV13 implementation in Ontario, our data suggest both direct and indirect effects on serotype-specific incidence in young children and older adults. However, overall provincial rates have remained unchanged, and IPD continues to be a severe burden on the population. The rising incidence of IPD due to PPV23 unique and non-vaccine-preventable serotypes, and the growing burden of serotypes 3 and 22F, require further study.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Little is known about the role of state versus trait characteristics on our enjoyment of music. The aim of this study was to investigate the influence of state and trait absorption upon preference ...for music, particularly preference for music that evokes negative emotions. The sample consisted of 128 participants who were asked to listen to two pieces of self-selected music and rate the music on variables including preference and felt and expressed emotions. Participants completed a brief measure of state absorption after listening to each piece, and a trait absorption inventory. State absorption was strongly positively correlated with music preference, whereas trait absorption was not. Trait absorption was related to preference for negative emotions in music, with chi-square analyses demonstrating greater enjoyment of negative emotions in music among individuals with high trait absorption. This is the first study to show that state and trait absorption have separable and distinct effects on a listener's music experience, with state characteristics impacting music enjoyment in the moment, and trait characteristics influencing music preference based on its emotional content.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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