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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.
High-starch diets (HSDs) fed to high-producing ruminants are often responsible for rumen dysfunction and could impair animal health and production. Feeding HSDs are often characterized by transient rumen pH depression, accurate monitoring of which requires costly or invasive methods. Numerous clinical signs can be followed to monitor such diet changes but no specific indicator is able to make a statement at animal level on-farm. The aim of this pilot study was to assess a combination of non-invasive indicators in dairy cows able to monitor a HSD in experimental conditions. A longitudinal study was conducted in 11 primiparous dairy cows fed with two different diets during three successive periods: a 4-week control period (P1) with a low-starch diet (LSD; 13% starch), a 4-week period with an HSD (P2, 35% starch) and a 3-week recovery period (P3) again with the LSD. Animal behaviour was monitored throughout the experiment, and faeces, urine, saliva, milk and blood were sampled simultaneously in each animal at least once a week for analysis. A total of 136 variables were screened by successive statistical approaches including: partial least squares-discriminant analysis, multivariate analysis and mixed-effect models. Finally, 16 indicators were selected as the most representative of a HSD challenge. A generalized linear mixed model analysis was applied to highlight parsimonious combinations of indicators able to identify animals under our experimental conditions. Eighteen models were established and the combination of milk urea nitrogen, blood bicarbonate and feed intake was the best to detect the different periods of the challenge with both 100% of specificity and sensitivity. Other indicators such as the number of drinking acts, fat:protein ratio in milk, urine, and faecal pH, were the most frequently used in the proposed models. Finally, the established models highlight the necessity for animals to have more than 1 week of recovery diet to return to their initial control state after a HSD challenge. This pilot study demonstrates the interest of using combinations of non-invasive indicators to monitor feed changes from a LSD to a HSD to dairy cows in order to improve prevention of rumen dysfunction on-farm. However, the adjustment and robustness of the proposed combinations of indicators need to be challenged using a greater number of animals as well as different acidogenic conditions before being applied on-farm.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Low atmospheric pressure stunning (LAPS) is a novel approach to pre-slaughter stunning of chickens using progressive hypobaric hypoxia by the application of gradual decompression (280s cycle) according to a set of prescribed pressure curves. Low atmospheric pressure stunning produces a non-recovery state. Concerns have been raised relating to the possible pathological and welfare consequences of expansion of air in the body during LAPS. In a randomised trial, we compared the gross pathology of broilers exposed to LAPS with a control group euthanised by intravenous injection of pentobarbital sodium (60 mixed sex broilers per treatment). The birds were exposed to each treatment in triplets and all birds were subject to necropsy examination to detect and score (1 to 5, minimal to severe) haemorrhagic lesions or congestion for all major organs and cavities (e.g. air sacs, joints, ears and heart) as well as external assessment for product quality (e.g. wing tips). Behavioural data (latency to loss of posture and motionless) and chamber cycle data (temperature, humidity, pressure and oxygen availability) confirmed that LAPS had been applied in a manner representative of the commercial process. All of the organs observed were structurally intact for both treatment groups. No lesions were observed in the external ears, oral cavity, tracheal lumen, crop and air sacs of birds from either treatment group. There was no difference between treatments in the wingtips, nasal turbinates, thymus, biceps femoralis and colon. Haemorrhagic lesions were observed in the calvaria, brains, hearts and lungs of both treatment groups, but lesions in these areas were more severe in the LAPS treatment group. It was not possible to distinguish between pathological changes induced by decompression or recompression. In the barbiturate group, more severe haemorrhagic lesions were observed in the superficial pectoral muscles as well as greater congestion of the infraorbital sinuses, liver, spleens, duodenum, kidneys and gonads. These findings provide evidence that LAPS did not result in distension of the intestines and air sacs sufficient to cause changes, which were grossly visible on postmortem examination. There was also no evidence of barotrauma in the ears and sinuses. The pathological changes observed in the barbiturate treatment were as expected based on barbiturate toxicity. Low atmospheric pressure stunning appears to produce pathological changes by a variety of well-established mechanisms, and while these pathological data have limited value as welfare indicators, the results confirm that organ integrity was not compromised by the process.
The mammal family Tenrecidae (Afrotheria: Afrosoricida) is endemic to Madagascar. Here we present the conservation priorities for the 31 species of tenrec that were assessed or reassessed in 2015–2016 for the IUCN Red List of Threatened Species. Six species (19.4%) were found to be threatened (4 Vulnerable, 2 Endangered) and one species was categorized as Data Deficient. The primary threat to tenrecs is habitat loss, mostly as a result of slash-and-burn agriculture, but some species are also threatened by hunting and incidental capture in fishing traps. In the longer term, climate change is expected to alter tenrec habitats and ranges. However, the lack of data for most tenrecs on population size, ecology and distribution, together with frequent changes in taxonomy (with many cryptic species being discovered based on genetic analyses) and the poorly understood impact of bushmeat hunting on spiny species (Tenrecinae), hinders conservation planning. Priority conservation actions are presented for Madagascar's tenrecs for the first time since 1990 and focus on conserving forest habitat (especially through improved management of protected areas) and filling essential knowledge gaps. Tenrec research, monitoring and conservation should be integrated into broader sustainable development objectives and programmes targeting higher profile species, such as lemurs, if we are to see an improvement in the conservation status of tenrecs in the near future.
Radio-echo sounding (RES) can be used to understand ice-sheet processes, englacial flow structures and bed properties, making it one of the most popular tools in glaciological exploration. However, RES data are often subject to ‘strip noise’, caused by internal instrument noise and interference, and/or external environmental interference, which can hamper measurement and interpretation. For example, strip noise can result in reduced power from the bed, affecting the quality of ice thickness measurements and the characterization of subglacial conditions. Here, we present a method for removing strip noise based on combined wavelet and two-dimensional (2-D) Fourier filtering. First, we implement discrete wavelet decomposition on RES data to obtain multi-scale wavelet components. Then, 2-D discrete Fourier transform (DFT) spectral analysis is performed on components containing the noise. In the Fourier domain, the 2-D DFT spectrum of strip noise keeps its linear features and can be removed with a ‘targeted masking’ operation. Finally, inverse wavelet transforms are performed on all wavelet components, including strip-removed components, to restore the data with enhanced fidelity. Model tests and field-data processing demonstrate the method removes strip noise well and, incidentally, can remove the strong first reflector from the ice surface, thus improving the general quality of radar data.
We present a workflow to track icebergs in proglacial fjords using oblique time-lapse photos and the Lucas-Kanade optical flow algorithm. We employ the workflow at LeConte Bay, Alaska, where we ran five time-lapse cameras between April 2016 and September 2017, capturing more than 400 000 photos at frame rates of 0.5–4.0 min−1. Hourly to daily average velocity fields in map coordinates illustrate dynamic currents in the bay, with dominant downfjord velocities (exceeding 0.5 m s−1 intermittently) and several eddies. Comparisons with simultaneous Acoustic Doppler Current Profiler (ADCP) measurements yield best agreement for the uppermost ADCP levels (~ 12 m and above), in line with prevalent small icebergs that trace near-surface currents. Tracking results from multiple cameras compare favorably, although cameras with lower frame rates (0.5 min−1) tend to underestimate high flow speeds. Tests to determine requisite temporal and spatial image resolution confirm the importance of high image frame rates, while spatial resolution is of secondary importance. Application of our procedure to other fjords will be successful if iceberg concentrations are high enough and if the camera frame rates are sufficiently rapid (at least 1 min−1 for conditions similar to LeConte Bay).
The analysis of multi-phase pharmaceuticals, particularly when similar structures are involved (i.e. polymorphs, salts or hydrates), can often be a difficult task. Historically, x-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) have been utilized to study pharmaceutical samples. Relative to other materials, diffraction data for pharmaceuticals are often complex due to the large number of diffraction maxima caused by the size of the molecule and/or the molecular symmetry. Multi-phase mixtures tend to have a large number of overlapping peaks which can hinder the difftactionist's ability to identify phases and interpret the data. When similar structures are analyzed calorimetrically, their thermal events may severely overlap (as will be shown), preventing accurate interpretation of the data. In addition there are several types of thermal events which may not be related to structural transitions. A common one in pharmaceuticals is the loss of solvent or absorbed (versus molecular) water.
Laboratory identification of carbapenem-resistant Enterobacteriaceae (CRE) is a key step in controlling its spread. Our survey showed that most Veterans Affairs laboratories follow VA guidelines for initial CRE identification, whereas 55.0% use PCR to confirm carbapenemase production. Most respondents were knowledgeable about CRE guidelines. Barriers included staffing, training, and financial resources.
of positive degree, we investigate the existence of auxiliary polynomials
factors as a product of polynomials of small relative degree. One consequence of this work shows that for any quadratic polynomial
, there are infinitely many
for which the largest prime factor of
is no larger than
Buprenorphine/samidorphan (BUP/SAM), a combination of BUP (a µ-opioid receptor partial agonist and κ-antagonist) and SAM (a sublingually bioavailable µ-opioid antagonist), is an investigational opioid system modulator for depression. BUP/SAM has shown efficacy versus placebo as an adjunctive treatment for major depressive disorder (MDD) and a consistent safety profile in previously reported, placebo-controlled clinical studies.1,2
1. To characterize the safety profile following long-term treatment with BUP/SAM
2. To explore depression symptoms and remission rates in patients with MDD following long-term treatment with BUP/SAM
FORWARD-2 (Clinicaltrials.gov ID: NCT02141399) enrolled patients who had participated in 1 of 4 controlled studies as well as de novo patients. All patients had a confirmed diagnosis of MDD, had a history of inadequate response to standard antidepressant therapies (ADTs), and had been treated with an adequate dose of an established ADT for ≥8weeks before BUP/SAM initiation. ADT dosage could be titrated, but the ADT could not be changed. During the study, patients received open-label, sublingual BUP/SAM 2mg/2mg as adjunctive treatment for up to 52weeks. Safety (primary objective) was assessed via adverse events (AEs), vital signs, laboratory analytes, and electrocardiography. Suicidal ideation or behavior (SIB) was evaluated by the Columbia Suicide Severity Rating Scale. Abuse potential, dependence, and withdrawal were assessed by AEs and the Clinical Opiate Withdrawal Scale. Exploratory efficacy endpoints included mean Montgomery–Åsberg Depression Rating Scale (MADRS) scores and remission rate (MADRS ≤10).
Of 1454 total patients, 49% completed the 52-week study, 11% discontinued due to an AE, and 40% discontinued because of other reasons as of the interim data cutoff date (April 30, 2017). Most AEs were of mild/moderate severity. Serious AEs were reported in 3.2% of patients. AEs occurring in ≥10% of patients were nausea, headache, constipation, dizziness, and somnolence. There was no evidence of increased risk of SIB with BUP/SAM. Incidence of euphoria-related events was low (1.2%). After abrupt discontinuation of BUP/SAM, there was little evidence of withdrawal. BUP/SAM was not associated with meaningful changes in laboratory or metabolic parameters or in bodyweight. The mean MADRS score decreased from 22.9 (±9.7) at baseline to 9.8 (±8.8) after 52weeks. The remission rate at 52weeks was 52.5%.
Long-term treatment with BUP/SAM did not reveal any new safety findings and confirmed that the risk of abuse and dependence with BUP/SAM was low. BUP/SAM maintained an antidepressant effect for up to 52weeks of treatment in patients with MDD.
Objective: To conduct a formative evaluation of a transitional intervention for family caregivers, with assessment of feasibility, acceptability, appropriateness, and potential benefits. Methods: The intervention aimed to provide emotional support, information on community resources, and information and support for development of coping skills for the caregivers of patients aged 65 and older who were to be discharged home from an acute medical hospital admission. We used a one-group, pre- and three-month post-test study design. Results: Ninety-one patient-caregiver dyads were recruited. Of these, 63 caregivers (69%) received all five planned intervention sessions, while 60 (66%) completed the post-test. There were significant reductions in caregiver anxiety and depression following the intervention, and high rates of satisfaction. Discussion: This transitional intervention should be further evaluated, preferably with a control group, either as a stand-alone intervention or as one component of a comprehensive transitional intervention for older patients and their caregivers.
OBJECTIVES/SPECIFIC AIMS: The purpose of this study was to characterize the pharmacokinetics of phosphatidylethanol (PEth) 16:0/20:4 homolog in uncoagulated, human blood samples taken from 18 participants in a clinical laboratory setting after consumption of 2 doses of ethanol. METHODS/STUDY POPULATION: Male and female participants received either 0.4 or 0.8 g/kg oral doses of ethanol during a 15-minute period. Blood samples were collected before and throughout 6 hours immediately after alcohol administration, then after 2, 4, 7, 11, and 14 days of administration day. PEth 16:0/20:4 levels were quantified by liquid mass spectrometry. Breath ethanol concentrations were measure concurrently with each blood collection during the administration day, as well as transdermal ethanol concentrations monitored constantly before, during and after ethanol administration day. RESULTS/ANTICIPATED RESULTS: (1) Single doses of 0.4 and 0.8 g ethanol/kg produced proportional increases in BrAC and PEth 16:0/20:4 levels; (2) the increase of Peth 16:0/20:4 from base line to Cmax was less than either PEth 16:0/18:1 or PEth 16:0/18:2 during the 6-hour period after ethanol administration; (3) the mean rate of formation of PEth 16:0/20:4 was lower than those of the other 2 homologs; (4) the mean half-life of PEth 16:0/20:4 was 2.18 days, which was shorter than that of either PEth 16:0/18:1 and PEth 16:0/18:2, which were 6.80 and 6.62, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: The results of this study further confirm that PEth homologs are a sensitive biomarker for ethanol consumption. The measurement of three PEth homologs appears to provide additional information about the level and time frame of drinking.
Background:ATP8A2 mutations have only recently been associated with human disease. We present the clinical features from the largest cohort of patients with this disorder reported to date. Methods: An observational study of 9 unreported and 2 previously reported patients with biallelic ATP8A2 mutations was carried out at multiple centres. Results: The mean age of the cohort was 9.4 years old (range: 2.5-28 yrs). All patients demonstrated developmental delay, severe hypotonia and movement disorders: chorea/choreoathetosis (100%), dystonia (27%) or facial dyskinesia (18%). Hypotonia was apparent at birth (70%) or before 6 months old (100%). Optic atrophy was observed in 75% of patients who had a funduscopic examination. MRI of the brain was normal for most patients with a small proportion showing mild cortical atrophy (30%), delayed myelination (20%) and/or hypoplastic optic nerves (20%). Epilepsy was seen in two older patients. Conclusions:ATP8A2 gene mutations have emerged as a cause of a novel phenotype characterized by developmental delay, severe hypotonia and hyperkinetic movement disorders. Optic atrophy is common and may only become apparent in the first few years of life, necessitating repeat ophthalmologic evaluation. Early recognition of the cardinal features of this condition will facilitate diagnosis of this disorder.
Introduction: Prehospital blood transfusion has been adopted by many civilian helicopter emergency medical service (HEMS) agencies and early outcomes are positive. Shock Trauma Air Rescue Service (STARS) operates six bases in Western Canada and in 2013 implemented a prehospital transfusion program. We describe the processes and standard work ensuring safe storage, administration, and stewardship of this precious resource. Our aim was to produce a sustainable and safe blood storage system that could be carried on each mission flown. Methods: Close collaboration with transfusion services and adherence to Canadian Transfusion Standards was key at each step of development. An inexpensive, reusable, temperature controlled thermal packaging device was obtained along with an electronic temperature logger. Conditioning of the device and temperature maintenance (1 6C) was tested to ensure safe storage conditions. Online training programs were developed for air medical crew (AMC) as well as transport physicians (TPs) regarding administration indications, safety, and stewardship processes. Blood traceability and usage was monitored on an ongoing basis for quality assurance. Results: Two units of O negative packed red blood cells (pRBCs) are now carried on each flight. The blood box is conditioned and prepared by transfusion services for routine exchange every 72 hours. If pRBCs are administered the blood bank is immediately notified for preparation of another cooler. Unused blood is returned to blood bank circulation. Conclusion: The introduction of the STARS blood on board program supports the provision of emergent transfusion to selected patients in the pre-hospital environment. Our standard work and stewardship processes minimize wastage of blood products while keeping it readily available for critically ill and injured patients. Subsequent work will aim to describe characteristics and patient centred outcomes.
This work presents a fully differential wideband and low power 240 GHz multiplier-by-8 chain, manufactured in IHP's 130 nm SiGe:C BiCMOS technology with fT/fmax = 300/500 GHz. A single ended 30 GHz input signal is multiplied by 8 using Gilbert cell-based quadrupler and doubler, and then amplified with a wideband differential 3-stage cascode amplifier. To achieve wide bandwidth and optimize for power consumption, the power budget has been designed in order to operate the frequency multipliers and the output amplifier in saturation. With this architecture the presented circuit achieves a 3 dB bandwidth of 40 GHz, meaning a relative 3 dB bandwidth of 17%, and a peak saturated output power of 0 dBm. Harmonic rejections better than 25 dB were measured for the 5th, 6th, and 7th harmonics. It dissipates 255 mW from 3 V supply which results in drain efficiency of 0.4%, while occupying 1.2 mm2. With these characteristics the presented circuit suits very well as a frequency multiplier chain for driving balanced mixers in 240 GHz transceivers for radar, communication, and sensing applications.
In horses, forages account for the greatest proportion of the diet (Micol and Martin-Rosset, 1995). As a result, the energy value of forages has to be determined very accurately to meet the horse requirements. In the UFC system (Horse Feed Unit) proposed by INRA (Martin-Rosset et al., 1994), the energy value of forages is closely related to organic matter digestibility (OMD).
In ruminants, OMD has been related to the in vitro gas production after 24 h of fermentation of foodstuffs with rumen fluid (Menke et al., 1979). The prediction of OMD with the gas test method is less accurate than with the nylon bag method but better than prediction performed with in vitro method or from chemical composition of foods (Khazaal et al., 1993 and 1995).
In the UFC system, three routine methods have been performed by our laboratory and proposed by INRA to predict routinely OMD of foodstuffs. OMD can be predicted either from chemical composition (Martin-Rosset et al., 1996a), by a pepsin cellulase method (Aufrère, 1982; Martin-Rosset et al., 1996b) or by near infra-red spectrometry (NIRS) (Andrieu et al., 1996).
The gas test method was subjected to be adapted in horses for predicting OMD. The accuracy of the prediction with the gas test method was compared with the other routine methods.