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Nordic twin studies have played a critical role in understanding cancer etiology and elucidating the nature of familial effects on site-specific cancers. The NorTwinCan consortium is a collaborative effort that capitalizes on unique research advantages made possible through the Nordic system of registries. It was constructed by linking the population-based twin registries of Denmark, Finland, Norway and Sweden to their country-specific national cancer and cause-of-death registries. These linkages enable the twins to be followed many decades for cancer incidence and mortality. To date, two major linkages have been conducted: NorTwinCan I in 2011–2012 and NorTwinCan II in 2018. Overall, there are 315,413 eligible twins, 57,236 incident cancer cases and 58 years of follow-up, on average. In the initial phases of our work, NorTwinCan established the world’s most comprehensive twin database for studying cancer, developed novel analytical approaches tailored to address specific research considerations within the context of the Nordic data and leveraged these models and data in research publications that provide the most accurate estimates of heritability and familial risk of cancers reported in the literature to date. Our findings indicate an excess familial risk for nearly all cancers and demonstrate that the incidence of cancer among twins mirrors the rate in the general population. They also revealed that twin concordance for cancer most often manifests across, rather than within, cancer sites, and we are currently focusing on the analysis of these cross-cancer associations.
The Norwegian Twin Registry (NTR) is maintained as a research resource that was compiled by merging several panels of twin data that were established for research into physical and mental health, wellbeing and development. NTR is a consent-based registry. Where possible, data that were collected in previous studies are curated for secondary research use. A particularly valuable potential benefit associated with the Norwegian twin data lies in the opportunities to expand and enhance the data through record linkage to nationwide registries that cover a wide array of health data and other information, including socioeconomic factors. This article provides a brief description of the current NTR sample and data collections, information about data access procedures and an overview of the national registries that can be linked to the NTR for research projects.
In electron beams where space charge plays an important role in the beam transport, the beams’ transverse and longitudinal properties will become coupled. One example of this is the transverse–longitudinal correlation produced in a current-modulated beam generated in a DC electron gun, formed through the competition between the time-dependent radial space charge force and the time-independent radial focusing force. This correlation will cause both the slice radius and divergence of the beam extracted from the gun to depend on the slice current. Here we consider the transport of such a beam in a linearly tapered solenoid focusing channel. Transport performance was generally improved with longer taper lengths, minimal initial correlation between slice divergence and slice current, and moderate degrees of initial correlation between initial slice radius and slice current. Performance was also generally improved with lower slice emittances, although surprisingly transport was improved by slightly increasing the assumed slice emittance in certain limited circumstances.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Substantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.
The present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2370 male and 2574 female UK Biobank participants.
There was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β = 0.191, q = 0.043). This was driven by a positive association between SCZ PRS and RACC thickness among MDD cases (β = 0.098, p = 0.026), compared to a negative association among controls (β = −0.087, p = 0.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.
Our significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.
The Nordic countries have comprehensive, population-based health and medical registries linkable on individually unique personal identity codes, enabling complete long-term follow-up. The aims of this study were to describe the NorTwinCan cohort established in 2010 and assess whether the cancer mortality and incidence rates among Nordic twins are similar to those in the general population. We analyzed approximately 260,000 same-sexed twins in the nationwide twin registers in Denmark, Finland, Norway and Sweden. Cancer incidence was determined using follow-up through the national cancer registries. We estimated standardized incidence (SIR) and mortality (SMR) ratios with 95% confidence intervals (CI) across country, age, period, follow-up time, sex and zygosity. More than 30,000 malignant neoplasms have occurred among the twins through 2010. Mortality rates among twins were slightly lower than in the general population (SMR 0.96; CI 95% [0.95, 0.97]), but this depends on information about zygosity. Twins have slightly lower cancer incidence rates than the general population, with SIRs of 0.97 (95% CI [0.96, 0.99]) in men and 0.96 (95% CI [0.94, 0.97]) in women. Testicular cancer occurs more often among male twins than singletons (SIR 1.15; 95% CI [1.02, 1.30]), while cancers of the kidney (SIR 0.82; 95% CI [0.76, 0.89]), lung (SIR 0.89; 95% CI [0.85, 0.92]) and colon (SIR 0.90; 95% CI [0.87, 0.94]) occur less often in twins than in the background population. Our findings indicate that the risk of cancer among twins is so similar to the general population that cancer risk factors and estimates of heritability derived from the Nordic twin registers are generalizable to the background populations.
X-ray fluorescence spectroscopy has been in use since the early days of the twentieth century, when Moseley confirmed the order of the chemical periodic table. However, fluorescence spectroscopy until recently has depended on diffraction methods to obtain sufficient resolution. Intrinsic resolution of ionization chambers, scintillation detectors, and proportional counters is inadequate for discrimination o f lines due to adjacent elements of low atomic number. The advent o f solid-state detectors, especially those using lithium-compensated silicon and low-noise electronics, has recently brought intrinsic energy resolution to the point where lines from adjacent elements as light as carbon and nitrogen can be resolved in theory; and detection of K radiation from elements as light as sodium is practical. Thus the solution to the long-standing problem of an adequate detector is at hand, and energy-dispersive spectrometers are now feasible.
Over the past 25 years, numerous studies utilizing both X-ray diffraction (XRE) and differential scanning calorimetry (DSC) have been reported In the literature. Generally, conventional high-temperature X-ray data identifies solid-state transitions, then attempts to correlate them with thermal events observed by the calorimeter. Since changes occur in the sample during studies such as these, separate portions of the sample must be used for XRD and DSC experiments. When comparing results of the two experiments, questions arise concerning sample homogeniety as well as temperature and environmental differences. In fact, no conventional high-temperature X-ray diffraction instrument can give the precise control over temperature and heating rate available with a DSC, The problems of sample inhomogeneltles and Instrumental differences could be avoided if X-ray diffraction and DSC could be performed simultaneously on one sample.
Objective: Few studies have investigated the assessment and functional impact of egocentric and allocentric neglect among stroke patients. This pilot study aimed to determine (1) whether allocentric and egocentric neglect could be dissociated among a sample of stroke patients using eye tracking; (2) the specific patterns of attention associated with each subtype; and (3) the nature of the relationship between neglect subtype and functional outcome. Method: Twenty acute stroke patients were administered neuropsychological assessment batteries, a pencil-and-paper Apples Test to measure neglect subtype, and an adaptation of the Apples Test with an eye tracking measure. To test clinical discriminability, twenty age- and education-matched control participants were administered the eye tracking measure of neglect. Results: The eye tracking measure identified a greater number of individuals as having egocentric and/or allocentric neglect than the pencil-and-paper Apples Test. Classification of neglect subtype based on eye tracking performance was a significant predictor of functional outcome beyond that accounted for by the neuropsychological test performance and Apples Test neglect classification. Preliminary evidence suggests that patients with no neglect symptoms had superior functional outcomes compared with patients with neglect. Patients with combined egocentric and allocentric neglect had poorer functional outcomes than those with either subtype. Functional outcomes of patients with either allocentric or egocentric neglect did not differ significantly. The applications of our findings, to improve neglect detection, are discussed. Conclusion: Results highlight the potential clinical utility of eye tracking for the assessment and identification of neglect subtype among stroke patients to predict functional outcomes. (JINS, 2019, 25, 479–489)
This replication study examined protective effects of positive childhood memories with caregivers (“angels in the nursery”) against lifespan and intergenerational transmission of trauma. More positive, elaborated angel memories were hypothesized to buffer associations between mothers’ childhood maltreatment and their adulthood posttraumatic stress disorder (PTSD) and depression symptoms, comorbid psychopathology, and children's trauma exposure. Participants were 185 mothers (M age = 30.67 years, SD = 6.44, range = 17–46 years, 54.6% Latina, 17.8% White, 10.3% African American, 17.3% other; 24% Spanish speaking) and children (M age = 42.51 months; SD = 15.95, range = 3–72 months; 51.4% male). Mothers completed the Angels in the Nursery Interview (Van Horn, Lieberman, & Harris, 2008), and assessments of childhood maltreatment, adulthood psychopathology, children's trauma exposure, and demographics. Angel memories significantly moderated associations between maltreatment and PTSD (but not depression) symptoms, comorbid psychopathology, and children's trauma exposure. For mothers with less positive, elaborated angel memories, higher levels of maltreatment predicted higher levels of psychopathology and children's trauma exposure. For mothers with more positive, elaborated memories, however, predictive associations were not significant, reflecting protective effects. Furthermore, protective effects against children's trauma exposure were significant only for female children, suggesting that angel memories may specifically buffer against intergenerational trauma from mothers to daughters.
Emergency physicians play an important role in providing care at the end-of-life as well as identifying patients who may benefit from a palliative approach. Several studies have shown that emergency medicine (EM) residents desire further training in palliative care. We performed a national cross-sectional survey of EM program directors. Our primary objective was to describe the number of Canadian postgraduate EM training programs with palliative and end-of-life care curricula.
A 15-question survey in English and French was sent by email to all program directors of both the Canadian College of Family Physicians emergency medicine (CCFP(EM)) and the Royal College of Physicians and Surgeons of Canada emergency medicine (RCPSC-EM) postgraduate training programs countrywide using FluidSurveys™ with a modified Dillman approach.
We received a total of 26 responses from the 36 (response rate = 72.2%) EM postgraduate programs in Canada. Ten out of 26 (38.5%) programs had a structured educational program pertaining to palliative and end-of-life care. Lectures or seminars were the exclusive choice to teach content. Clinical palliative medicine rotations were mandatory in one out of 26 (3.8%) programs. The top two barriers to implementation of palliative and end-of-life care curricula were lack of time (84.6%) and curriculum development concerns (80.8%).
Palliative and end-of-life care training within EM has been identified as an area of need. This cross-sectional survey demonstrates that a minority of Canadian EM programs have palliative and end-of-life care curricula. It will be important for all EM training programs, RCPSC-EM and CCFP(EM), in Canada, to develop an agreed upon set of competencies and to structure their curricula around them.
To identify potential participants for clinical trials, electronic health records (EHRs) are searched at potential sites. As an alternative, we investigated using medical devices used for real-time diagnostic decisions for trial enrollment.
To project cohorts for a trial in acute coronary syndromes (ACS), we used electrocardiograph-based algorithms that identify ACS or ST elevation myocardial infarction (STEMI) that prompt clinicians to offer patients trial enrollment. We searched six hospitals’ electrocardiograph systems for electrocardiograms (ECGs) meeting the planned trial’s enrollment criterion: ECGs with STEMI or > 75% probability of ACS by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI). We revised the ACI-TIPI regression to require only data directly from the electrocardiograph, the e-ACI-TIPI using the same data used for the original ACI-TIPI (development set n = 3,453; test set n = 2,315). We also tested both on data from emergency department electrocardiographs from across the US (n = 8,556). We then used ACI-TIPI and e-ACI-TIPI to identify potential cohorts for the ACS trial and compared performance to cohorts from EHR data at the hospitals.
Receiver-operating characteristic (ROC) curve areas on the test set were excellent, 0.89 for ACI-TIPI and 0.84 for the e-ACI-TIPI, as was calibration. On the national electrocardiographic database, ROC areas were 0.78 and 0.69, respectively, and with very good calibration. When tested for detection of patients with > 75% ACS probability, both electrocardiograph-based methods identified eligible patients well, and better than did EHRs.
Using data from medical devices such as electrocardiographs may provide accurate projections of available cohorts for clinical trials.
To determine the continued need for active surveillance to prevent extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-E) transmission in a neonatal intensive care unit (NICU).
This retrospective observational study included patients with ESBL-E colonization or infection identified during their NICU stay at our institution between 1999 and March 2018. Active surveillance was conducted between 1999 and March 2017 by testing rectal swab specimens collected upon admission and weekly thereafter. The overall incidence rates, of ESBL-E colonization or infection (including hospital acquired) before and after active surveillance were calculated. The cost associated with active surveillance was then estimated.
Overall, 171 NICU patients were found to have ESBL-E colonization or infection, and 150 of those patients (87.7%) were detected by active surveillance. The overall incidence rate was 1.4 per 100 patient admissions. The hospital-acquired incidence rate was 0.41 per 1,000 patient days, and this rate had decreased since 2002, with an average of 6 cases detected annually. A significant decrease was observed in 2009 when the unit moved to a new single-bed unit featuring private rooms. Active surveillance was discontinued with no increase in the number of infections. Of the 150 ESBL-E colonized patients, 14 (9.3%) subsequently developed an infection. Active surveillance resulted in a total of 50,950 specimen collections and a cost of $127,187 for processing, an average of $848 to detect 1 ESBL-E colonized patient.
ESBL-E transmission and infection in our NICU remains uncommon. Active surveillance may have contributed to the decline of ESBL-E transmission when used in conjunction with contact precautions and private rooms, but its relatively high cost could be prohibitive.
Internal gravity wave energy contributes significantly to the energy budget of the oceans, affecting mixing and the thermohaline circulation. Hence it is important to determine the internal wave energy flux
is the pressure perturbation field and
is the velocity perturbation field. However, the pressure perturbation field is not directly accessible in laboratory or field observations. Previously, a Green’s function based method was developed to calculate the instantaneous energy flux field from a measured density perturbation field
, given a constant buoyancy frequency
. Here we present methods for computing the instantaneous energy flux
for an internal wave field with vertically varying background
, as in the oceans where
typically decreases by two orders of magnitude from the pycnocline to the deep ocean. Analytic methods are presented for computing
from a density perturbation field for
varying linearly with
. To generalize this approach to arbitrary
, we present a computational method for obtaining
. The results for
for the different cases agree well with results from direct numerical simulations of the Navier–Stokes equations. Our computational method can be applied to any density perturbation data using the MATLAB graphical user interface ‘EnergyFlux’.
To establish the prevalence of hypocalcaemia following laryngectomy and demonstrate that total thyroidectomy is a risk factor.
A retrospective cohort study was conducted that included all patients who underwent total laryngectomy from 1st January 2006 to 1st August 2017. Exclusion criteria were: pre-operative calcium derangement, previous thyroid or parathyroid surgery, concurrent glossectomy, pharyngectomy, or oesophagectomy.
Ninety patients were included. Sixteen patients had early hypocalcaemia (18 per cent), seven had protracted hypocalcaemia (8 per cent) and six had permanent hypocalcaemia (10 per cent). Exact logistic regression values for hypocalcaemia following total thyroidectomy compared to other patients were: early hypocalcaemia, odds ratio = 15.5 (95 per cent confidence interval = 2.2–181.9; model p = 0.002); protracted hypocalcaemia, odds ratio = 13.3 (95 per cent confidence interval = 1.5–117.1; model p = 0.01); and permanent hypocalcaemia, odds ratio = 22.7 (95 per cent confidence interval = 1.9–376.5; model p = 0.005).
This is the largest study to investigate the prevalence of hypocalcaemia following laryngectomy and the first to include follow up of longer than three months. Total thyroidectomy significantly increased the risk of hypocalcaemia at all time frames and independent of other variables.
The Canadian Stroke Best Practice Recommendations suggests that patients suspected of transient ischemic attack (TIA)/minor stroke receive urgent brain imaging, preferably computed tomography angiography (CTA). Yet, high requisition rates for non-cerebrovascular patients overburden limited radiological resources, putting patients at risk. We hypothesize that our clinical decision support tool (CDST) developed for risk stratification of TIA in the emergency department (ED), and which incorporates Canadian guidelines, could improve CTA utilization.
Retrospective study design with clinical information gathered from ED patient referrals to an outpatient TIA unit in Victoria, BC, from 2015-2016. Actual CTA orders by ED and TIA unit staff were compared to hypothetical CTA ordering if our CDST had been used in the ED upon patient arrival.
For 1,679 referrals, clinicians ordered 954 CTAs. Our CDST would have ordered a total of 977 CTAs for these patients. Overall, this would have increased the number of imaged-TIA patients by 89 (10.1%) while imaging 98 (16.1%) fewer non-cerebrovascular patients over the 2-year period. Our CDST would have ordered CTA for 18 (78.3%) of the recurrent stroke patients in the sample.
Our CDST could enhance CTA utilization in the ED for suspected TIA patients, and facilitate guideline-based stroke care. Use of our CDST would increase the number of TIA patients receiving CTA before ED discharge (rather than later at TIA units) and reduce the burden of imaging stroke mimics in radiological departments.