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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.
Background: Cervical sponylotic myelopathy (CSM) may present with neck and arm pain. This study investiagtes the change in neck/arm pain post-operatively in CSM. Methods: This ambispective study llocated 402 patients through the Canadian Spine Outcomes and Research Network. Outcome measures were the visual analogue scales for neck and arm pain (VAS-NP and VAS-AP) and the neck disability index (NDI). The thresholds for minimum clinically important differences (MCIDs) for VAS-NP and VAS-AP were determined to be 2.6 and 4.1. Results: VAS-NP improved from mean of 5.6±2.9 to 3.8±2.7 at 12 months (P<0.001). VAS-AP improved from 5.8±2.9 to 3.5±3.0 at 12 months (P<0.001). The MCIDs for VAS-NP and VAS-AP were also reached at 12 months. Based on the NDI, patients were grouped into those with mild pain/no pain (33%) versus moderate/severe pain (67%). At 3 months, a significantly high proportion of patients with moderate/severe pain (45.8%) demonstrated an improvement into mild/no pain, whereas 27.2% with mild/no pain demonstrated worsening into moderate/severe pain (P <0.001). At 12 months, 17.4% with mild/no pain experienced worsening of their NDI (P<0.001). Conclusions: This study suggests that neck and arm pain responds to surgical decompression in patients with CSM and reaches the MCIDs for VAS-AP and VAS-NP at 12 months.
Background: Cervical spondylotic myelopathy (CSM) is the leading cause of spinal cord impairment. In a public healthcare system, wait times to see spine specialists and eventually access surgical treatment for CSM can be substantial. The goals of this study were to determine consultation wait times (CWT) and surgical wait times (SWT), and identify predictors of wait time length. Methods: Consecutive patients enrolled in the Canadian Spine Outcomes and Research Network (CSORN) prospective and observational CSM study from March 2015 to July 2017 were included. A data-splitting technique was used to develop and internally validate multivariable models of potential predictors. Results: A CSORN query returned 264 CSM patients for CWT. The median was 46 days. There were 31% mild, 35% moderate, and 33% severe CSM. There was a statistically significant difference in median CWT between moderate and severe groups; 207 patients underwent surgical treatment. Median SWT was 42 days. There was a statistically significant difference in SWT between mild/moderate and severe groups. Short symptom duration, less pain, lower BMI, and lower physical component score of SF-12 were predictive of shorter CWT. Only baseline pain and medication duration were predictive of SWT. Both CWT and SWT were shorter compared to a concurrent cohort of lumbar stenosis patients (p <0.001). Conclusions: Patients with shorter duration (either symptoms or medication) and less neck pain waited less to see a spine specialist in Canada and to undergo surgical treatment. This study highlights some of the obstacles to overcome in expedited care for this patient population.
Probabilistic approaches to phylogenetic inference have recently gained traction in paleontological studies. Because they directly model processes of evolutionary change, probabilistic methods facilitate a deeper assessment of variability in evolutionary patterns by weighing evidence for competing models. Although phylogenetic methods used in paleontological studies have generally assumed that evolution proceeds by splitting cladogenesis, extensions to previous models help explore the potential for morphological and temporal data to provide differential support for contrasting modes of evolutionary divergence. Recent methodological developments have integrated ancestral relationships into probabilistic phylogenetic methods. These new approaches rely on parameter-rich models and sophisticated inferential methods, potentially obscuring the respective contributions of data and models. In this study, we describe a simple likelihoodist approach that combines probabilistic models of morphological evolution and fossil preservation to reconstruct both cladogenetic and anagenetic relationships. By applying this approach to a data set of fossil hominins, we demonstrate the capability of existing models to unveil evidence for anagenesis presented by morphological and temporal data. This evidence was previously recognized by qualitative assessments, but largely ignored by quantitative phylogenetic analyses. For example, we find support for directly ancestral relationships in multiple lineages: Sahelanthropus is ancestral to later hominins; Australopithecus anamensis is ancestral to Australopithecus afarensis; Australopithecus garhi is ancestral to Homo; Homo antecessor is ancestral to Homo heidelbergensis, which in turn is ancestral to both Homo sapiens and Homo neanderthalensis. By accommodating direct ancestry in phylogenetics, quantitative results align more closely with previous qualitative expectations.
Background: Buprenorphine/naloxone (bup/nal) is a partial opioid agonist/antagonist and recommended first line treatment for opioid use disorder (OUD). Emergency departments (EDs) are a key point of contact with the healthcare system for patients living with OUD. Aim Statement: We implemented a multi-disciplinary quality improvement project to screen patients for OUD, initiate bup/nal for eligible individuals, and provide rapid next business day walk-in referrals to addiction clinics in the community. Measures & Design: From May to September 2018, our team worked with three ED sites and three addiction clinics to pilot the program. Implementation involved alignment with regulatory requirements, physician education, coordination with pharmacy to ensure in-ED medication access, and nurse education. The project is supported by a full-time project manager, data analyst, operations leaders, physician champions, provincial pharmacy, and the Emergency Strategic Clinical Network leadership team. For our pilot, our evaluation objective was to determine the degree to which our initiation and referral pathway was being utilized. We used administrative data to track the number of patients given bup/nal in ED, their demographics and whether they continued to fill bup/nal prescriptions 30 days after their ED visit. Addiction clinics reported both the number of patients referred to them and the number of patients attending their referral. Evaluation/Results: Administrative data shows 568 opioid-related visits to ED pilot sites during the pilot phase. Bup/nal was given to 60 unique patients in the ED during 66 unique visits. There were 32 (53%) male patients and 28 (47%) female patients. Median patient age was 34 (range: 21 to 79). ED visits where bup/nal was given had a median length of stay of 6 hours 57 minutes (IQR: 6 hours 20 minutes) and Canadian Triage Acuity Scores as follows: Level 1 – 1 (2%), Level 2 – 21 (32%), Level 3 – 32 (48%), Level 4 – 11 (17%), Level 5 – 1 (2%). 51 (77%) of these visits led to discharge. 24 (47%) discharged patients given bup/nal in ED continued to fill bup/nal prescriptions 30 days after their index ED visit. EDs also referred 37 patients with OUD to the 3 community clinics, and 16 of those individuals (43%) attended their first follow-up appointment. Discussion/Impact: Our pilot project demonstrates that with dedicated resources and broad institutional support, ED patients with OUD can be appropriately initiated on bup/nal and referred to community care.
The last 12 years have seen the evolution of a new funding regime under the supervision of the Pensions Regulator. Over this period, there has been significant turbulence in financial markets, including record low interest rates. This paper takes a critical look at the development of funding approaches and methodologies over this period. It analyses the Pensions Regulator guidance and how scheme specific actuarial methods have emerged since the move away from the Minimum Funding Requirement in 2001 and the introduction of the Scheme Specific Funding Requirements in 2005. It asks whether these new methodologies have been successful from the perspective of members, trustees, employers and shareholders. At a time when actuarial valuation methodologies have faced considerable criticism, this paper aims to propose a pension funding methodology which is fit for purpose and also reflects the latest guidance from the Pensions Regulator on integrated risk management.
The forward rate of dissolution of the International Simple Glass (ISG) was determined under alkaline conditions at 40 °C using the Single Pass Flow Through (SPFT) method. Forward rates were consistent with those obtained in the literature for this glass composition. The formation of altered gel layers and surface pits was observed on the surface of glass particles, especially at the very highest pH values, despite the application of high flow rates to prevent the build-up of solubility limiting phases. These features could be attributed to preferential localized dissolution at sites with a higher alkali concentration or from a separate, less durable, vitreous phase. These results may indicate that surface pit and altered gel formation occurs under the forward rate of dissolution as imposed by the SPFT method, particularly for simplified borosilicate glass materials.
We analyzed intestinal contents of two late-glacial mastodons preserved in lake sediments in Ohio (Burning Tree mastodon) and Michigan (Heisler mastodon). A multi-proxy suite of macrofossils and microfossils provided unique insights into what these individuals had eaten just before they died and added significantly to knowledge of mastodon diets. We reconstructed the mastodons’ habitats with similar multi-proxy analyses of the embedding lake sediments. Non-pollen palynomorphs, especially spores of coprophilous fungi differentiated intestinal and environmental samples. The Burning Tree mastodon gut sample originates from the small intestine. The Heisler mastodon sample is part of the large intestine to which humans had added clastic material to anchor parts of the carcass under water to cache the meat. Both carcasses had been dismembered, suggesting that the mastodons had been hunted or scavenged, in line with other contemporaneous mastodon finds and the timing of early human incursion into the Midwest. Both mastodons lived in mixed coniferous-deciduous late-glacial forests. They browsed tree leaves and twigs, especially Picea. They also ate sedge-swamp plants and drank the lake water. Our multi-proxy estimates for a spring/summer season of death contrast with autumn estimates derived from prior tusk analyses. We document the recovered fossil remains with photographs.
Highly resolved, well-dated paleoclimate records from the southern South African coast are needed to contextualize the evolution of the highly diverse extratropical plant communities of the Greater Cape Floristic Region (GCFR) and to assess the environmental impacts on early human hunter-gatherers. We present new speleothem stable oxygen and carbon isotope ratios (δ18Oc and δ13C) from two caves at Pinnacle Point, South Africa, covering the time between 330 and 43 ka. Composite δ18Oc and δ13C records were constructed for Staircase Cave and PP29 by combining all stable isotope analyses into a single time series and smoothing by a 3-point running mean. δ18Oc and δ13C values record changes in rainfall seasonality and the proportions of C3 and C4 plants in the vegetation, respectively. We show that in general increased summer rainfall brought about a wider spread of C4 grasses and retreat of the C3 plant–dominated GCFR communities. The occurrence of summer rainfall on the southern coast of South Africa was linked to total rainfall amounts in the interior region through tropical temperate troughs. These rainfall systems shifted the southern coastal climate toward more summer (winter) rainfall when precession was high (low) and/or the westerlies were in a northern (southern) position.
Highly anomalous platinum-group element (PGE) concentrations in the podiform chromitites at the Cliff and Harold's Grave localities in the Shetland ophiolite complex have been well documented previously. The focus of this study is alluvial platinum-group minerals (PGM) located in small streams that drain from the PGE-rich chromitites. The placer PGM assemblage at Cliff is dominated by Pt-arsenides (64%) and Pd-antimonides (17%), with less irarsite–hollingworthite (11%) and minor Pd-sulfides, Pt–Pd–Cu and Pt–Fe alloys and laurite. Gold also occurs with the PGM. Alluvial PGM have average sizes of 20 µm × 60 µm, with sperrylite the largest grain identified at 110 µm in diameter, matching the range reported for the primary PGM in the source rocks. The placer assemblage contains more Pt-bearing and less Pd-bearing PGM compared with the rocks. The more resistant sperrylite and irarsite–hollingworthite grains which are often euhedral become more rounded further downstream whereas the less resistant Pd-antimonides which are commonly subhedral may become striated and etched. Less stable phases such as Pt- and Pd-oxides and other Ni-Cu-bearing phases located in the rocks (i.e. Ru-pentlandite, PtCu, Pd–Cu alloy) are absent in the placer assemblage. Also the scarce PGM (PdHg, Rh- and Ir-Sb) and Os in the rocks are absent. At Harold's Grave only three alluvial PGM (laurite, Ir, Os) and Au were recovered reflecting the limited release of IPGM from chromite grains in the rocks. In this cold climate with high rainfall, where erosion dominates over weathering, the PGM appear to have been derived directly from the erosion of the adjacent PGE-rich source rocks and there is little evidence of in situ growth of any newly formed PGM. Only the presence of dendritic pure Au and Pd-, Cu-bearing Au covers on the surface of primary minerals may indicate some local reprecipitation of these metals in the surficial conditions.
Inclusions of platinum-group minerals (PGM) within alluvial isoferroplatinum nuggets from the Freetown Peninsula, Sierra Leone, are aligned with their shape determined by the structure of their host. The edges of the majority of the inclusions lie at 0°, 45° or 90° to external crystal edges of the nugget which shows that the inclusions are not randomly oriented earlier minerals incorporated within their host. The inclusions are later infills, probably formed at the surface of the nugget during growth and subsequently enclosed by the growing nugget. PGM on the present surface of the nugget represent the last stage of this partnership. A single nugget containing abundant inclusions is described here but similar features are observed in other nuggets from the same area. The inclusions contain laurite (RuS2), irarsite–hollingworthite (IrAsS–RhAsS), Pd–Te–Bi–Sb phases, Ir-alloy, Os-alloy, Pd-bearing Au, an Rh–Te phase, Pd–Au alloy and Pd–Pt–Cu alloy. PGM found on the nugget surface include laurite, irarsite and cuprorhodsite (CuRh2S4). The Pd–Te–Bi–Sb phases may include Sb-rich keithconnite (Pd20S7) and compositions close to the kotulskite–sobolevskite solid-solution series (PdTe–BiTe). Textural evidence suggests that formation of the nuggets began with the isoferroplatinum host and the voids were filled starting intergrowths of laurite and irarsite–hollingworthite with both laurite and irarsite–hollingworthite often showing compositional zonation and each of them replacing the other. Filling of the voids probably continued with Pd-Cu-bearing gold, Sb-rich keithconnite (Pd,Pt)20.06(Te,Sb,Bi)6.94, keithconnite, telluropalladinite Pd9(Te,Bi)4, RhTe and finally Ir-alloy and then Os-alloy. The nuggets are thought to be neoform growths in the organic- and bacterial-rich soils of the tropical rain forest cover of the Freetown intrusion. The mineralogical assemblage in the layered gabbros of the intrusion has been previously shown to differ from the alluvial assemblage in the rivers and these inclusions, not seen in Pt3Fe in the unaltered rocks, add a further item to the catalogue of differences.
We revise the data fitting in our original paper [The dissolution rates of simulated UK Magnox - ThORP blend nuclear waste glass as a function of pH, temperature and waste loading, Miner. Mag.79 (2015) 1529–1542]. The intrinsic rate constant data were calculated incorrectly, the corrected data are presented herein. To support the corrected analysis we have also taken the opportunity to report some additional 90°C data. The conclusions of the original paper remain sound.
Heavy mineral concentrates from rivers and river terraces near York, Freetown Peninsula, Sierra Leone have been examined for their platinum-group mineral (PGM) content. The alluvial PGM are 0.1 to 1.5 mm in size and include Cu-bearing isoferroplatinum (Pt3Fe) and disordered Pt3–xFe (x ≤ 0.38), tulameenite (Pt2FeCu), hongshiite (PtCu), cooperite–vysotskite (PtS–PdS), laurite (RuS2), erlichmanite (OsS2), Os-Ir alloy, Os-Ru alloy and native copper.
Are the alluvial nuggets primary or a neoformation? Comparison of the PGM mineralogy of fresh rocks, weathered rocks and the saprolite, with the alluvial suite shows strongly contrasting features highlighted by the mineral assemblage. Cooperite in the fresh rocks is rare in the alluvium whilst Pt-Fe alloys become more abundant. Oxidized PGM are a feature only of the weathering process and disordering of the Pt-Fe alloys develops during weathering. Palladium is much less abundant in the alluvial suite than in the primary minerals whereas Cu, present as Cu-sulfides in the fresh rocks, occurs in the alluvium as a minor component of the Pt-Fe alloys and as hongshiite alteration to the Pt-Fe alloys. The size difference is striking; the primary mineralogy is micrometre-sized whereas the alluvial PGM are three orders of magnitude larger. Delicate PGM with alteration textures are seen only in the weathered rocks whilst delicate dendritic PGM are reported only from the alluvial suite. An organic coating to the alluvial PGM may be indicative of an organic or bacterial involvement. Some alluvial PGM occur in a drainage basin devoid of outcrops of PGE-bearing horizons.
Together these contrasting features of the primary and placer PGM support the proposal that the Freetown nuggets developed as a result of breakdown of the primary PGM during weathering, movement of the PGE in solution, and growth of new PGM in placers with a different mineral assemblage, mineralogy and mineral chemistry.
Although childhood adversity is a potent determinant of psychopathology, relatively little is known about how the characteristics of adversity exposure, including its developmental timing or duration, influence subsequent mental health outcomes. This study compared three models from life course theory (recency, accumulation, sensitive period) to determine which one(s) best explained this relationship.
Prospective data came from the Avon Longitudinal Study of Parents and Children (n = 7476). Four adversities commonly linked to psychopathology (caregiver physical/emotional abuse; sexual/physical abuse; financial stress; parent legal problems) were measured repeatedly from birth to age 8. Using a statistical modeling approach grounded in least angle regression, we determined the theoretical model(s) explaining the most variability (r2) in psychopathology symptoms measured at age 8 using the Strengths and Difficulties Questionnaire and evaluated the magnitude of each association.
Recency was the best fitting theoretical model for the effect of physical/sexual abuse (girls r2 = 2.35%; boys r2 = 1.68%). Both recency (girls r2 = 1.55%) and accumulation (boys r2 = 1.71%) were the best fitting models for caregiver physical/emotional abuse. Sensitive period models were chosen alone (parent legal problems in boys r2 = 0.29%) and with accumulation (financial stress in girls r2 = 3.08%) more rarely. Substantial effect sizes were observed (standardized mean differences = 0.22–1.18).
Child psychopathology symptoms are primarily explained by recency and accumulation models. Evidence for sensitive periods did not emerge strongly in these data. These findings underscore the need to measure the characteristics of adversity, which can aid in understanding disease mechanisms and determining how best to reduce the consequences of exposure to adversity.
Objectives: People with Huntington’s disease (HD) experience poor social quality of life, relationship breakdown, and social withdrawal, which are mediated to some extent by socially debilitating neuropsychiatric symptoms, such as apathy and disinhibition. Social cognitive symptoms, such as impaired emotion recognition, also occur in HD, however, the extent of their association with these socially debilitating neuropsychiatric symptoms is unknown. Our study examined the relationship between emotion recognition and symptom ratings of apathy and disinhibition in HD. Methods: Thirty-two people with premanifest or symptomatic-HD completed Part 1 of The Awareness of Social Inference Test (TASIT), which is a facial emotion recognition task. In addition, we obtained severity ratings for apathy and disinhibition on the Frontal Systems Behavior Scale (FrSBe) from a close family member. Our analyses used motor symptom severity as a proxy for disease progression. Results: Emotion recognition performance was significantly associated with family-ratings of apathy, above and beyond their shared association with disease severity. We found a similar pattern for disinhibition ratings, which fell short of statistical significance. As expected, worse emotion recognition performance was correlated with higher severity in FrSBe symptom ratings. Conclusions: Our findings suggest that emotion recognition abilities relate to key socially debilitating neuropsychiatric symptoms in HD. Our results help to understand the functional significance of emotion recognition impairments in HD, and may have implications for the development of remediation programs aimed at improving patients’ social quality of life. (JINS, 2018, 24, 417–423)
A “stone in the pond” strategy is a practical approach to investigating large-scale nosocomial tuberculosis (TB) exposures. Here, we describe such a risk-stratified approach to contact tracing after a TB exposure that occurred over 5 months in a pediatric inpatient ward in a country with a moderate TB burden.
X-ray computed tomography (CT) measurements of live sheep have been used to predict carcass composition very accurately (Macfarlane et al., 2006). The utilisation of spiral CT scans (SCTS) for quantifying muscle volumes and weights, using automatic image analysis procedures has also been shown to be very accurate in sheep (Navajas et al., 2006). Although the limiting size of the CT gantry prevents CT scanning of live beef cattle, beef primal joints are small enough to be scanned. Hence, SCTS could be used to quantify beef carcass composition, and provide valuable information for breeding programmes including composition faster than by anatomical dissection. The objective of this study was to develop a CT image analysis procedure to assess fat, muscle and bone weights of beef carcasses and to evaluate its accuracy.