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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.
Little is known about long-term employment outcomes for patients with first-episode schizophrenia-spectrum (FES) disorders who received early intervention services.
We compared the 10-year employment trajectory of patients with FES who received early intervention services with those who received standard care. Factors differentiating the employment trajectories were explored.
Patients with FES (N = 145) who received early intervention services in Hong Kong between 1 July 2001 and 30 June 2002 were matched with those who entered standard care 1 year previously. We used hierarchical clustering analysis to explore the 10-year employment clusters for both groups. We used the mixed model test to compare cluster memberships and piecewise regression analysis to compare the employment trajectories of the two groups.
There were significantly more patients who received the early intervention service in the good employment cluster (early intervention: N = 98 [67.6%]; standard care: N = 76 [52.4%]; P = 0.009). In the poor employment cluster, there was a significant difference in the longitudinal pattern between early intervention and standard care for years 1–5 (P < 0.0001). The number of relapses during the first 3 years, months of full-time employment during the first year and years of education were significant in differentiating the clusters of the early intervention group.
Results suggest there was an overall long-term benefit of early intervention services on employment. However, the benefit was not sustained for all patients. Personalisation of the duration of the early intervention service with a focus on relapse prevention and early vocational reintegration should be considered for service enhancement.
Declaration of interests
No relevant conflicts of interests reported by C.L.M.H., Y.N.S., P.S., H.H.P. and K.K.Y. S.K.W.C., W.C.C. and E.H.M.L. report that they are members of the working group of the Early Assessment Service for Young People with Psychosis (EASY) programme of the Hospital Authority in Hong Kong. E.Y.H.C. is the convener of the working group of the EASY programme of the Hospital Authority in Hong Kong.
Andrew Harding, in his excursus on ‘legal transplantation’, observed: ‘[W]e do live in a world of legal connectivity in which we share common problems which can only be addressed by a limited range of solutions which are unlikely not to have been tried before’. This prescient remark is apt in the context of the growing importance of the proportionality concept in the Australian public law arena. The proportionality concept attained particular prominence when the High Court of Australia found a freedom of political communication impliedly embedded in the Constitution. It was inevitable that with the establishment of such an implied fundamental constitutional guarantee, the High Court had to craft a principle to enable the saving or invalidation of legislation claimed to be in violation of the implied freedom.
The psycholinguistic rationale proposed for TBLT varies somewhat, but is usually an amalgam of cognitive-interactionist and usage-based theories (see, e.g., Long, 2015a, pp. 30–62; Robinson, 2007, 2015; Skehan, 1998, 2015) developed with language learning as the explanandum. When students are adults, whose capacity for purely incidental learning, especially instance learning, is weaker than in young children, a variety of devices is required to enhance incidental learning and thereby speed up the process. The enhancements seek to help learners either detect or notice new items in the input by increasing their perceptual saliency and by drawing learners’ attention to needed lexis and collocations and grammatical patterns, especially when non-salient forms and form–function or form–meaning relationships are concerned. However, most of the attention-drawing procedures are deployed in response to learner performance, not in advance, as in synthetic approaches.
The objective of the present study is to summarise trends in under- and over-nutrition in pregnant women on the Thailand–Myanmar border. Refugees contributed data from 1986 to 2016 and migrants from 1999 to 2016 for weight at first antenatal consultation. BMI and gestational weight gain (GWG) data were available during 2004–2016 when height was routinely measured. Risk factors for low and high BMI were analysed for <18·5 kg/m2 or ≥23 kg/m2, respectively. A total of 48 062 pregnancies over 30 years were available for weight analysis and 14 646 pregnancies over 13 years (2004–2016) had BMI measured in first trimester (<14 weeks’ gestational age). Mean weight at first antenatal consultation in any trimester increased over the 30-year period by 2·0 to 5·2 kg for all women. First trimester BMI has been increasing on average by 0·5 kg/m2 for refugees and 0·6 kg/m2 for migrants, every 5 years. The proportion of women with low BMI in the first trimester decreased from 16·7 to 12·7 % for refugees and 23·1 to 20·2 % for migrants, whereas high BMI increased markedly from 16·9 to 33·2 % for refugees and 12·3 to 28·4 % for migrants. Multivariate analysis demonstrated low BMI as positively associated with being Burman, Muslim, primigravid, having malaria during pregnancy and smoking, and negatively associated with refugee as opposed to migrant status. High BMI was positively associated with being Muslim and literate, and negatively associated with age, primigravida, malaria, anaemia and smoking. Mean GWG was 10·0 (sd 3·4), 9·5 (sd 3·6) and 8·3 (sd 4·3) kg, for low, normal and high WHO BMI categories for Asians, respectively.
Background: There is an unmet need for blood-based biomarkers that can reliably detect MS disease activity. Serum Biomarkers of interest includ Neurofilament-light-chain (NfL), Glial-fibrillary-strocyte-protein(GFAP) and Tau. Bone Marrow Transplantation (BMT) is reserved for aggressive forms of MS and has been shown to halt detectable CNS inflammatory activity for prolonged periods. Significant pre-treatment tissue damage at followed by inflammatory disease abeyance should be reflected longitudinal sera collected from these patients. Methods: Sera were collected from 23 MS patients pre-treatment, and following BMT at 3, 6, 9 and 12-months in addition from 33 non-inflammatory neurological controls. Biomarker quantification was performed with SiMoA. Results: Pre-AHSCT levels of serum NfL and GFAP but not Tau were elevated compared to controls (p=0.0001), and NfL correlated with lesion-based disease activity (6-month-relapse, MRI-T2 and Gadolinium-enhancement). 3-months post-treatment, while NfL levels remained elevated, Tau/GFAP paradoxically increased (p=0.0023/0.0017). These increases at 3m correlated with MRI ‘pseudoatrophy’ at 6-months. NfL/Tau levels dropped to that of controls by 6-months (p=0.0036/0.0159). GFAP levels dropped progressively after 6-months although even at 12-months remained higher than controls (p=0.004). Conclusions: NfL was the closest correlate of MS disease activity and treatment response. Chemotherapy-related toxicity may account for transient increases in NfL, Tau and MRI brain atrophy post-BMT.
Norovirus, a major cause of gastroenteritis in people of all ages worldwide, was first reported in South Korea in 1999. The most common causal agents of pediatric acute gastroenteritis are norovirus and rotavirus. While vaccination has reduced the pediatric rotavirus infection rate, norovirus vaccines have not been developed. Therefore, prediction and prevention of norovirus are very important. Norovirus is divided into genogroups GI–GVII, with GII.4 being the most prevalent. However, in 2012–2013, GII.17 showed a higher incidence than GII.4 and a novel variant, GII.P17-GII.17, appeared. In this study, 204 stool samples collected in 2013–2014 were screened by reverse transcriptase-polymerase chain reaction; 11 GI (5.39%) and 45 GII (22.06%) noroviruses were identified. GI.4, GI.5, GII.4, GII.6 and GII.17 were detected. The whole genomes of the three norovirus GII.17 were sequenced. The whole genome of GII.17 consists of three open reading frames of 5109, 1623 and 780 bp. Compared with 20 GII.17 strains isolated in other countries, we observed numerous changes in the protruding P2 domain of VP1 in the Korean GII.17 viruses. Our study provided genome information that might aid in epidemic prevention, epidemiology studies and vaccine development.
We report an experimental investigation of pressure-driven flow of a viscous liquid across thin polydimethylsiloxane (PDMS) membranes. Our experiments revealed a nonlinear relation between the flow rate
and the applied pressure drop
, in apparent disagreement with Darcy’s law, which dictates a linear relationship between flow rate, or average velocity, and pressure drop. These observations suggest that the effective permeability of the membrane decreases with pressure due to deformation of the nanochannels in the PDMS polymeric network. We propose a model that incorporates the effects of pressure-induced deformation of the hyperelastic porous membrane at three distinct scales: the membrane surface area, which increases with pressure, the membrane thickness, which decreases with pressure, and the structure of the porous material, which is deformed at the nanoscale. With this model, we are able to rationalize the deviation between Darcy’s law and the data. Our result represents a novel case in which macroscopic deformations can impact the microstructure and transport properties of soft materials.
We investigated whether neurobehavioral markers of risk for emotion dysregulation were evident among newborns, as well as whether the identified markers were associated with prenatal exposure to maternal emotion dysregulation. Pregnant women (N = 162) reported on their emotion dysregulation prior to a laboratory assessment. The women were then invited to the laboratory to assess baseline respiratory sinus arrhythmia (RSA) and RSA in response to an infant cry. Newborns were assessed after birth via the NICU Network Neurobehavioral Scale. We identified two newborn neurobehavioral factors—arousal and attention—via exploratory factor analysis. Low arousal was characterized by less irritability, excitability, and motor agitation, while low attention was related to a lower threshold for auditory and visual stimulation, less sustained attention, and poorer visual tracking abilities. Pregnant women who reported higher levels of emotion dysregulation had newborns with low arousal levels and less attention. Larger decreases in maternal RSA in response to cry were also related to lower newborn arousal. We provide the first evidence that a woman's emotion dysregulation while pregnant is associated with risks for dysregulation in her newborn. Implications for intergenerational transmission of emotion dysregulation are discussed.
Introduction: Many drugs, including cannabis and alcohol, cause impairment and contribute to motor vehicle collisions (MVCs). Policy makers require knowledge of the prevalence of drug use in crash-involved drivers, and types of drugs used in order to develop effective prevention programs. This issue is particularly relevant with the recent legalization of cannabis. We aim to study the prevalence of alcohol, cannabis, sedating medications, and other drugs in injured drivers from 4 Canadian Provinces. Methods: This prospective cohort study obtained excess clinical blood samples from consecutive injured drivers who attended a participating Canadian trauma centre following a MVC. Blood samples were analyzed using a broad spectrum toxicology screen capable of detecting cannabinoids, cocaine, amphetamines (including their major analogues), and opioids as well as psychotropic pharmaceuticals (including antihistamines, benzodiazepines, other hypnotics, and sedating antidepressants). Alcohol and cannabinoids were quantified. Health records were reviewed to extract demographic, medical, and MVC information using a standardized data collection tool. Results: This study has been collecting data in 4 trauma centres in British Columbia (BC) since 2011 and was launched in 2 trauma centres in Alberta (AB), 1 in Saskatchewan (SK), and 2 in Ontario (ON) in 2018. In preliminary results from BC (n = 2412), 8% of injured drivers tested positive for THC and 13% for alcohol. Preliminary results from other provinces (n = 301) suggest a regional variation in prevalence of drivers testing positive for THC (10% - 27%), alcohol (17% - 29%), and other drugs. By May 2018, an estimated 4500 cases from BC, 600 from AB, 150 from SK, and 650 from ON will have been analyzed. We will report the prevalence of positive tests for alcohol, THC, other recreational drugs, and sedating medications, pre and post cannabis legalization. The number of cases with alcohol and/or THC levels above Canadian per se limits will also be reported. Results will be reported according to province, driver sex, age, single vs. multi vehicle crashes, and requirement for hospital admission. Conclusion: This will be among the largest international datasets on drug use by injured drivers. Our findings will provide patterns of drug and alcohol impairment in 4 Canadian provinces pre and post cannabis legalization. The significance of these findings and implication for impaired driving policy and prevention programs in Canada will be discussed.
Introduction: Individualizing risk for stroke following a transient ischemic attack (TIA) is a topic of intense research, as existing scores are context-dependent or have not been well validated. The Canadian TIA Score stratifies risk of subsequent stroke into low, moderate and high risk. Our objective was to prospectively validate the Canadian TIA Score in a new cohort of emergency department (ED) patients. Methods: We conducted a prospective cohort study in 14 Canadian EDs over 4 years. We enrolled consecutive adult patients with an ED visit for TIA or nondisabling stroke. Treating physicians recorded standardized clinical variables onto data collection forms. Given the ability of prompt emergency carotid endarterectomy (CEA) to prevent stroke (NNT = 3) in high risk patients, our primary outcome was the composite of subsequent stroke or CEA ≤7 days. We conducted telephone follow-up using the validated Questionnaire for Verifying Stroke Free Status at 7 and 90 days. Outcomes were adjudicated by panels of 3 local stroke experts, blinded to the index ED data collection form. Based on prior work, we estimated a sample size of 5,004 patients including 93 subsequent strokes, would yield 95% confidence bands of +/− 10% for sensitivity and likelihood ratio (LR). Our analyses assessed interval LRs (iLR) with 95% CIs. Results: We prospectively enrolled 7,569 patients with mean 68.4 +/−14.7 years and 52.4% female, of whom 107 (1.4%) had a subsequent stroke and 74 (1.0%) CEA ≤7 days (total outcomes = 181). We enrolled 81.2% of eligible patients; missed patients were similar to enrolled. The Canadian TIA Score stratified the stroke/CEA ≤7days risk as: Low (probability <0.2%, iLR 0.20 [95%CI 0.091-0.44]; Moderate (probability 1.3%, iLR 0.79 [0.68-0.92]; High (probability 2.6%, iLR 2.2 [1.9-2.6]. Sensitivity analysis for just stroke ≤7 days yielded similar results: Low iLR 0.17 [95%CI 0.056-0.52], Medium iLR 0.89 [0.75-1.1], High iLR 2.0 [1.6-2.4]. Conclusion: The Canadian TIA Score accurately identifies TIA patients risk for stroke/CEA ≤7 days. Patients classified as low risk can be safely discharged following a careful ED assessment with elective follow-up. Patients at moderate risk can undergo additional testing in the ED, have antithrombotic therapy optimized, and be offered early stroke specialist follow-up. Patients at high risk should in most cases be fully investigated and managed ideally in consultation with a stroke specialist during their index ED visit.
To determine the factors related to multiple ventilation tube insertions in children with otitis media with effusion.
A retrospective review was performed of 126 ears of 81 children aged less than 12 years who had undergone insertion of a Paparella type 1 ventilation tube for the first time between August 2012 and March 2018.
Mean age at the first operation was 4.0 ± 2.2 years, and the mean duration of otitis media with effusion before the first ventilation tube insertion was 5.4 ± 4.5 months. Among 126 ears, 80 (63.5 per cent) had a single ventilation tube insertion and 46 (36.5 per cent) had multiple insertions. On multivariate logistic regression, tympanic membrane retraction, serous middle-ear discharge, and early recurrence of otitis media with effusion were independent predictive factors of multiple ventilation tube insertions.
Tympanic membrane retraction, serous middle-ear discharge, and early recurrence of otitis media with effusion after the first tube extrusion are associated with multiple ventilation tube insertions.
Increasingly, products are designed for global markets, yet studies of design practices primarily investigate designers from high-income countries. Specifically, the use of prototypes during design is likely affected by the background of the designer and the environment in which they are designing. To broaden our understanding of the extent to which prototyping best practices are used beyond Western designers, in this study, we conducted interviews with novice designers from Ghana, a middle-income country (MIC), to examine how Ghanaian novice designers (upper-level undergraduate students) used prototypes throughout their design courses. We compared the reported use of prototypes to best practice behaviors and analyzed the types of prototypes used. We found evidence that these Ghanaian novice designers used some critical prototyping best practice behaviors, while other behaviors were underutilized, specifically during the front-end phases of design and for the purpose of engaging with stakeholders. Additionally, virtual models dominated their prototyping choices. We discuss likely reasons for these trends based on participants’ design experiences and design contexts.
In this study, an improved fluid–structure interaction (FSI) analysis method is developed for a flapping wing. A co-rotational (CR) shell element is developed for its structural analysis. Further, a relevant non-linear dynamic formulation is developed based on the CR framework. Three-dimensional preconditioned Navier–Stokes equations are employed for its fluid analysis. An implicit coupling scheme is employed to combine the structural and fluid analyses. An explicit investigation of a 3D plunging wing is conducted using this FSI analysis method. A further investigation of this plunging wing is performed in relation to its operating condition. In addition, the relation between the wing’s aerodynamic performance and plunging motion is investigated.
A new ESCA (electron spectroscopy for chemical analysis) instrument has been developed to provide high sensitivity and efficient operation for laboratory analysis of composition and chemical bonding in very thin surface layers of solid samples. High sensitivity is achieved by means of the high-intensity, efficient X-ray source described by Davies and Herglotz at the 1968 Denver X-Ray Conference, in combination with the new electron energy analyzer described by Lee at the 1972 Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy. A sample chamber designed to provide for rapid introduction and replacement of samples has adequate facilities for various sample treatments and conditioning followed immediafely by ESCA analysis of the sample.
Examples of application are presented, demonstrating the sensitivity and resolution achievable with this instrument. Its usefulness in trace surface analysis is shown and some “chemical shifts” measured by the instrument are compared with those obtained by X-ray spectroscopy.
Identifying routes of transmission among hospitalized patients during a healthcare-associated outbreak can be tedious, particularly among patients with complex hospital stays and multiple exposures. Data mining of the electronic health record (EHR) has the potential to rapidly identify common exposures among patients suspected of being part of an outbreak.
We retrospectively analyzed 9 hospital outbreaks that occurred during 2011–2016 and that had previously been characterized both according to transmission route and by molecular characterization of the bacterial isolates. We determined (1) the ability of data mining of the EHR to identify the correct route of transmission, (2) how early the correct route was identified during the timeline of the outbreak, and (3) how many cases in the outbreaks could have been prevented had the system been running in real time.
Correct routes were identified for all outbreaks at the second patient, except for one outbreak involving >1 transmission route that was detected at the eighth patient. Up to 40 or 34 infections (78% or 66% of possible preventable infections, respectively) could have been prevented if data mining had been implemented in real time, assuming the initiation of an effective intervention within 7 or 14 days of identification of the transmission route, respectively.
Data mining of the EHR was accurate for identifying routes of transmission among patients who were part of the outbreak. Prospective validation of this approach using routine whole-genome sequencing and data mining of the EHR for both outbreak detection and route attribution is ongoing.
Periodontitis, or conventionally “Gum Disease,” is the infection and inflammation of gingival tissue, and is currently the leading cause of tooth loss in the United States. One of the most effective treatments of periodontitis is guided bone regeneration (GBR); however, current GBR barrier membranes lack high biocompatibility and cell impermeability. The authors of this study evaluated the in vitro viability of previously synthesized Gelatin-Pluronic® F127 hybrid hydrogels as potential GBR barrier membranes through a novel three-partition test involving migration of fluorescent-dyed human dermal fibroblasts. Results showed that cells were unable to migrate across the Gelatin-Pluronic® F127 hybrid hydrogel barrier, whereas control setups with gelatin hydrogel barriers showed cell permeability. In addition, cytotoxicity tests were conducted with fibroblasts plated in both cell mediums that had been incubated while in contact hybrid gels and cell mediums suspended on the surface of hybrid gels during swelling procedures. Fluorescence cell plate readings showed similar cell viability across data from both tests, indicating that Gelatin-Pluronic® F127 hybrid hydrogels are not toxic to cells, and thus biocompatible.
This study evaluated tumour necrosis factor-α, interleukins 10 and 12, and interferon-γ levels, peripheral blood mononuclear cells, and clusters of differentiation 17c and 86 expression in unilateral sudden sensorineural hearing loss.
Twenty-four patients with unilateral sudden sensorineural hearing loss, and 24 individuals with normal hearing and no history of sudden sensorineural hearing loss (who were attending the clinic for other problems), were enrolled. Peripheral blood mononuclear cells, and clusters of differentiation 11c and 86 were isolated and analysed. Plasma and supernatant levels of tumour necrosis factor-α, interferon-γ, and interleukins 10 and 12 were measured.
There were no significant differences with respect to age and gender. Monocyte population, mean tumour necrosis factor-α level and cluster of differentiation 86 expression were significantly increased in the study group compared to the control group. However, interferon-γ and interleukin 12 levels were significantly decreased. The difference in mean interleukin 10 level was not significant.
Increases in tumour necrosis factor-α level and monocyte population might play critical roles in sudden sensorineural hearing loss. This warrants detailed investigation and further studies on the role of dendritic cells in sudden sensorineural hearing loss.
Research suggests intergenerational links between childhood abuse and neglect and subsequent parenting quality, but little is known about the potential mechanisms underlying intergenerational continuities in parenting. Adult romantic functioning may be one plausible mechanism, given its documented associations with both adverse caregiving in childhood and parenting quality in adulthood. The present study used data from the Minnesota Longitudinal Study of Risk and Adaptation to (a) investigate prospective associations between childhood experiences of abuse and neglect and multiple parenting outcomes in adulthood, and (b) evaluate the degree to which adult romantic functioning mediates those associations. Information regarding childhood abuse and neglect was gathered prospectively from birth through age 17.5 years. Multimethod assessments of romantic functioning were collected repeatedly through early adulthood (ages 20 to 32 years), and parenting quality was assessed as participants assumed a parenting role (ages 21 to 38 years). As expected, childhood abuse and neglect experiences predicted less supportive parenting (observed and interview rated) and higher likelihood of self-reported Child Protective Services involvement. The association with interview-rated supportive parenting was partially mediated by lower romantic competence, whereas the association with Child Protective Services involvement was partially mediated by more relational violence in adult romantic relationships. Implications of these novel prospective findings for research and clinical intervention are discussed.