HostSeq: a Canadian whole genome sequencing and clinical data resource.

HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community for health research through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.

Intuitive wireless control of a robotic arm for people living with an upper body disability.

Assistive Technologies (ATs) also called extrinsic enablers are useful tools for people living with various disabilities. The key points when designing such useful devices not only concern their intended goal, but also the most suitable human-machine interface (HMI) that should be provided to users. This paper describes the design of a highly intuitive wireless controller for people living with upper body disabilities with a residual or complete control of their neck and their shoulders. Tested with JACO, a six-degree-of-freedom (6-DOF) assistive robotic arm with 3 flexible fingers on its end-effector, the system described in this article is made of low-cost commercial off-the-shelf components and allows a full emulation of JACO's standard controller, a 3 axis joystick with 7 user buttons. To do so, three nine-degree-of-freedom (9-DOF) inertial measurement units (IMUs) are connected to a microcontroller and help measuring the user's head and shoulders position, using a complementary filter approach. The results are then transmitted to a base-station via a 2.4-GHz low-power wireless transceiver and interpreted by the control algorithm running on a PC host. A dedicated software interface allows the user to quickly calibrate the controller, and translates the information into suitable commands for JACO. The proposed controller is thoroughly described, from the electronic design to implemented algorithms and user interfaces. Its performance and future improvements are discussed as well.

Stable and Intuitive Control of an Intelligent Assist Device.

Safety and dependability are of the utmost importance for physical human-robot interaction due to the potential risks that a relatively powerful robot poses to human beings. From the control standpoint, it is possible to improve safety by guaranteeing that the robot will never exhibit any unstable behavior. However, stability is not the only concern in the design of a controller for such a robot. During human-robot interaction, the resulting cooperative motion should be truly intuitive and should not restrict in any way the human performance. For this purpose, we have designed a new variable admittance control law that guarantees the stability of the robot during constrained motion and also provides a very intuitive human interaction. The former characteristic is provided by the design of a stability observer while the latter is based on a variable admittance control scheme that uses the time derivative of the contact force to assess human intentions. The stability observer is based on a previously published stability investigation of cooperative motion which implies the knowledge of the interaction stiffness. A method to accurately estimate this stiffness online using the data coming from the encoder and from a multiaxis force sensor at the end effector is also provided. The stability and intuitivity of the control law are verified in a user study involving a cooperative drawing task with a 3 degree-of-freedom (dof) parallel robot as well as in experiments performed with a prototype of an industrial Intelligent Assist Device.

Building materials as intrinsic sources of sulphate: a hidden face of salt weathering of historical monuments investigated through multi-isotope tracing (B, O, S).

Sulphate neoformation is a major factor of degradation of stone monuments. Boron, sulphur and oxygen isotope signatures were investigated for five French historical monuments (Bourges, Chartres and Marseille cathedrals, Chenonceau castle, and Versailles garden statues) to investigate the role of intrinsic sulphate sources (gypsum plasters and mortars) in stone degradation, compared to the influence of extrinsic sources such as atmospheric pollution. Gypsum plasters and gypsum-containing mortars fall systematically in the δ(34)S and δ(18)O range of Paris Basin Eocene evaporites indicating the origin of the raw materials (so-called "Paris plaster"). Black crusts show the typical S and O isotope signatures observed elsewhere in Europe that can be attributed to atmospheric pollution, together with a marine component for Marseille. Boron isotopes for black crusts indicate coal combustion as principal boron source. Mortar isotope compositions discriminate three types, one similar to gypsum plasters, one strongly depleted in (34)S, attributed to pyrite oxidation, and a third one close to atmospheric sulphates. The isotopic composition of sulphates and boron of most degraded building stones of the different monuments is well explained by the identified sulphate sources. In several cases (in particular for Chenonceau and Bourges, to some extent for Chartres), the impact of gypsum plaster as building and restoration material on the degradation of the stones in its vicinity was clearly demonstrated. The study illustrates the usefulness of multi-isotope studies to investigate stone degradation factors, as the combination of several isotope systematics increases the discriminatory power of isotope studies with respect to contaminant sources.

Weight loss maintenance in women two to eleven years after participating in a commercial program: a survey.

BACKGROUND: After 5 years, most reports show that less than 10% of people maintain a 5% loss from initial body weight. Weight maintenance after 10 years is rarely assessed, especially in commercial programs. The current article reports weight maintenance in individuals who had participated 2 to 11 years earlier in a popular commercial weight loss program based on Canada's Food Guide called Mincavi. METHODS: Randomly picked subjects answered a telephone questionnaire. Participants, 291 adult women from various regions of the province of Quebec, had followed the program 2 to 11 years earlier for at least a month. Body weight at the beginning and at the end of treatment was recorded as well as actual weight, age and height. Existing records allowed partial verification of the sample. RESULTS: Based on corrected weights, percentage of women who maintained at least 5% of their initial weight loss are as following; 2 years = 43.6% (n = 55), 3 years = 33.3% (n = 42), 4 years = 23.8% (n = 42), 5-6 years = 38.2% (n = 55), 7-8 years = 29.4% (n = 51), and 9-11 years; 19.6% (n = 46). Five to eleven years after they had participated in the program 29.1% of all women maintained a weight loss of at least 5%, while 14.3% maintained a loss of at least 10%. CONCLUSIONS: Even though success rate is not as high as could be wished for, results show that participation in the Mincavi program can lead to effective weight maintenance long after individuals have left it. These findings suggest more thorough studies should be conducted on this weight loss program.

"Outings to your taste": a nutrition program for the elderly.

"Outings to Your Taste" is an innovative program that aims to improve the nutritional status and social network of elderly people who receive home-delivered meals. This article examines participation in one of the program's components, outings to community restaurants. Participation data were collected on-site and information about client characteristics was collected in at-home interview surveys of targeted clients (n = 144). While about half of the clients had tried at least one outing, more than 25% of them participated in at least one third of the outings offered to them. Results indicate that the program attracted a variety of clients in terms of sociodemographic, health, and social isolation characteristics.

Lipostat in the lean rat: evidence for a non-causal relationship between glucocorticoids and leptin levels.

In order to assess the long-term impact of a complete depletion of glucocorticoids on plasma leptin levels, we bilaterally adrenalectomized 20 lean rats, and analysed glucocorticoids and leptin levels for 20 consecutive days. Results demonstrate that the adrenalectomy (ADX) significantly lowered the leptin levels, as compared to sham-operated controls. On the other hand, a significant increase in leptin levels was noticeable from day 1 to day 20 of the experiment in the sham-operated controls, even though corticosterone levels remained stable during that same period. Plasma leptin concentration was proportional to body fat content. These results would indicate a non-causal relationship between glucocorticoids and leptin levels in the context of a lipostat in the lean rat.

The Unbearable Weight on Your Mind: The Physiological Dimension of Body Image Disturbances.

The ideal body, according to Western society's standards of physical appearance, has become increasingly thinner. Body image disturbances, a phenomenon often associated with today's society's standards of thinness, are common among obese and eating-disordered subjects, and have recently been documented in normal weight subjects. The aim of this review is to propose a new biological interpretation of body image disturbances, not presenting them as a mere consequence of society's pressure to be thin, but as a result of body weight regulation. Early in life, a "set-point-related body image" that may be described as a schematized representation of one's body weight set-point, would be created by the central nervous system. This unconscious representation of one's body size and mass, would later act as an internal reference in processing weight relevant information. External cues concerning body weight (e.g. visual information regarding one's body shape) as well as internal cues (e.g. moving one's body against gravity) would both be compared, by the central nervous system, to the set-point-related body image. A difference between actual body size and setpoint-related body image could generate an "error signal" that would lead to body image disturbances. These disturbances, reflecting the error signal of the regulatory system, would in turn trigger corrective metabolic and behavioral mechanisms working to return body weight to set-point.

Corticotropin Releasing Hormone and Body Weight Regulation: The Behavioral Approach.

In 1996, Cabanac and Richard revived Hervey's then 25-year old hypothesis explaining the stability of body weight through regulation of blood corticosteroid concentrations. They suggested that glucocorticoids are the regulated variable, the concentration of which ensures body weight stability, and they proposed a descriptive model of this regulation. Because steroids are soluble in lipids, it follows that their concentration in the body depends in part on the volume of lipids stored. Low fat stores increase the glucocorticoid concentration in the blood and, conversely, high fat stores lower the glucocorticoid concentration. Hypothalamic corticotropin-releasing hormone (CRH) and body weight could thus be the final step in the sequence initiated by glucocorticoid regulation. Alternatively, glucocorticoids stimulate leptin production by the adipocytes. The rise in leptin secretion increases hypothalamic CRH production, which lowers the set-point for body weight. In both cases, it may be hypothesized that hypothalamic CRH concentration defines the set-point for body weight regulation. Since 1996, Richard has studied the histological aspects of the hypothesis. In this article we present the results of our behavioral experiments to test the hypothesis. The results of all the experiments support this hypothesis.

Hoarding behavior in obese and control rats: evidence indicating cost differences.

Hoarding behavior of rats can be described by the equation y = ax + b, where y is the amount of food hoarded, x the rat's body weight, a the negative slope of the regression line, and b, the ordinate at zero abscissa. We repeatedly evaluated the parameters of this equation in six obese Zucker rats and six controls, from 8 to 32 weeks of age. The mean slope of the regression lines remained close to -11 in both groups of rats, until 24 weeks of age. From then on, the slopes of the obese rats decreased dramatically to c. -3, and remained as such for the rest of the experiment, while that of controls remained constant. At this age (24 weeks), controls weighed 453 +/- 14 g and obese rats 729 +/- 18 g. We suggest that the decreased slope of hoarding in obese rats was due to an increased cost of the hoarding behavior.

Adrenalectomy lowers the body weight set-point in rats.

In order to evaluate the impact of a complete depletion of glucocorticoids on rats' body weight set-point, rats were adrenalectomized, and their set-points were estimated before, and after surgery. Body weight set-points were obtained from a quantitative behavioral method based on the rats' food-hoarding response to weight deficit. In addition, body fat contents were measured in vivo using a total body electrical conductivity analyzer (TOBEC). The hoarding of food showed that adrenalectomized rats had significantly lower body weight set-points than the sham-operated controls (337 +/- 11 g vs. 385 +/- 8 g) and were also significantly lighter. TOBEC measurements showed that the sham-operated control rats had a higher body fat content than the adrenalectomized rats ( 16.7 +/- 1.1% vs. 10.2 +/- 1.2%). The present study demonstrates that adrenalectomy lowers the body weight set-point in rats, suggesting that the concentrations of glucocorticoid hormones, and in turn, the hypothalamic corticotrophin releasing hormone (CRH) participates in the adjustment of the body weight set-point.

Platelet deposition on ePTFE grafts coated with fibrin glue with or without FGF-1 and heparin.

INTRODUCTION: The disappointing long-term patency of small-caliber prosthetic grafts may be due in part to early thrombogenicity of the prosthetic surface. We previously reported that the coating of expanded polytetrafluoroethylene (ePTFE) with fibrin glue (FG) containing fibroblast growth factor type 1 (FGF-1) and heparin accelerated spontaneous endothelial coverage of ePTFE grafts in an animal model; however, FG's effect on platelets remains unclear. This study was done to evaluate platelet deposition onto GF/FGF-1/ heparin-coated vs FG-coated vs whole-blood-preclotted ePTFE surfaces. METHODS: Twelve 5-cm ePTFE grafts were treated either with FG (thrombin, 0.32 U/ ml, and fibrinogen, 32.1 mg/ml, n = 8) or with FG containing FGF-1 (11 ng/ml) plus heparin (250U/ml, n = 4). Twelve control ePTFE grafts were preclotted with canine (n = 8) or human (n = 4) whole blood. These treated grafts were placed onto a loop pulsatile perfusion system in pairs (preclotted with either FG or FG/ FGF-1/heparin) and perfused with a M-199/10% FBS/ 111indium-labeled platelet suspension. After 60 min the grafts were gamma counted and CPM/mm2 were determined. RESULTS: In both trials, the preclotted ePTFE grafts demonstrated similarly increased platelet deposition when compared to grafts treated with FG/FGF-1/heparin or FG alone (P < 0.001 for each). CONCLUSION: The decrease in platelet deposition on the FG/FGF-1/ heparin-coated grafts vs preclotted grafts is not due to heparin and is not specific to canine or human platelets. FG-coated grafts may induce a decrease in early graft thrombogenicity when compared to whole blood preclotting.

Effect of pulsatile pressure on the breaking strength and movement of Prolene sutures.

PURPOSE: Most studies of sutures used in vascular surgery have used steadily applied loads. But in vivo, sutures are subject to pulsatile pressures. Pulsatile pressures could weaken sutures, or they could be beneficial by helping to slide the suture, thereby equilibrating the tension between unevenly tightened loops. This study examined the effect of pulsatile pressures on the strength and movement of polypropylene (Prolene) sutures. METHODS: Segments of pig thoracic aorta were cannulated and studied in a tissue bath in vitro at 37 degrees C. A longitudinal arteriotomy was made and then closed with running 6-0 Prolene. Vessels were subjected to (1) no pressure; (2) 100 mm Hg steady pressure; or (3) 112/65 mm Hg pulsatile pressure. After 48 hours the sutures were studied for breaking strength. In a second, separate set of experiments, longitudinal arteriotomies were closed using running suture lines. These were constructed with either several loose loops or several overly tight loops. Fine wires were affixed to the suture loops to permit photographic recording of suture movement. RESULTS: There was no difference in breaking force among 68 sutures that had been subjected to (1) no pressure; (2) 100 mm Hg steady pressure; or (3) 112/65 mm Hg pulsatile pressure. These also were no different than sutures that were not sewn into arteries. These findings indicate that neither steady nor pulsatile pressures weaken Prolene sutures. In the second set of experiments, it was found that pulsatile pressure did cause movement of suture lines where there were loose loops (p < 0.05). However, neither steady nor pulsatile pressures caused movement of loops in suture lines that contained normal and overly tight loops. CONCLUSIONS: Neither steady nor pulsatile physiologic pressures weaken 6-0 Prolene sutures that have been used to close a longitudinal arteriotomy. These pressures can cause movement of loose suture lines, but do not equilibrate the tension between normal and overly tight suture loops. Overly tight loops may place excessive load on a suture line.

Ponderostat: hoarding behavior satisfies the condition for a lipostat in the rat.

The mass of food hoarded by rats given access to food only two hours per day is proportional to the rats' body weight deficit. The present work investigated whether this behavior might reflect the amount of body fat rather than body weight. The hoarding behavior of three rats was measured every other day at various body weights. After each hoarding session the animals were anesthetized and their percentage of fat was measured in vivo with a total body electrical conductivity method (TOBEC). The results showed that the amount of food hoarded in the two-hour sessions was inversely proportional to the fat content of the body. This result shows that, in the rat, the fat stored is correlated with the behavioral response leading to the defence of body weight, and therefore satisfies a condition necessary for a lipostat.

Ever higher: constant rise of body weight set-point in growing zucker rats.

The mass of food hoarded by rats given access to food only 2 h per day is proportional to the rats' body weight deficit. The intersect of the regression line of hoarded food plotted against body weight gives an indication of the body weight set-point. In the present work, the hoarding behavior of six obese and six control rats was measured every day at various body weights from 8 to 24 weeks of age. Every other week the animals were anesthetized and their percentage of fat was measured in vivo with a total body electrical conductivity method (TOBEC). Lean mass and body length of the obese, and their controls, increased similarly in both groups over the period of the measurements. On the other hand, the body weights increased more in obese, from 174 +/- 5 to 729 +/- 18 g (n = 6), than in controls, from 157 +/- 5 g to 452 +/- 14 g (n = 6). The body weight set-point, calculated every other week for both groups of rats, increased progressively with age. At the age of 24 weeks, the mean set-point for body weight regulation was 758 +/- 13 g in obese and 467 +/- 12 g in controls. This result suggests that the obese fa/fa rat defends its fat content, or a variable correlated to the fat content.

ePTFE coating with fibrin glue, FGF-1, and heparin: effect on retention of seeded endothelial cells.

In an attempt to improve the resistance of seeded endothelial cell (EC) to desquamation due to shear stress, we evaluated the effect of coating expanded polytetrafluoroethylene (ePTFE) grafts with fibrin glue (FG) containing fibroblast growth factor 1 (FGF1) and heparin on the retention of EC exposed to pulsatile flow ex vivo. Five pairs of ePTFE grafts (30 microm internodal distance, 4 mm internal diameter, 7 cm long) were coated with either FG/FGF-1/heparin (fibrinogen 32.1 mg/ml, thrombin 0.32 U/ml, FGF-1 11 ng/ml, heparin 250 U/ml) or fibronectin (FN) (20 microgram/ml). Canine jugular vein endothelial cells (Factor VIII, passages 5-7), were radiolabeled with indium-111 (100 microCi/1 million cells). Cell seeding (3 x 10(5) cells/cm2) was achieved by four successive inoculations of cells separated by 90 degree graft rotations. After overnight incubation (37 degrees C), pairs of FG and FN grafts (5 cm long) were simultaneously perfused ex vivo with culture media containing 10% fetal bovine serum (120/80 mm Hg, 90 cc/min, 60 pulsations/min). During the 1-hr perfusion, perfusate samples were taken at 0, 5, 15, 30, and 60 min to determine radioactivity loss. Pre- and postperfusion whole graft radioactivity data were compared to estimate cell retention and confirmed by histologic evaluation. Mean adherent radioactivity on FG-coated grafts (96 +/- 5%) was significantly higher (P = 0.0029, Student's t test) than on FN-coated grafts (85 +/- 3%). Maximum radioactivity loss in perfusate was seen after 5 min, with lower sustained loss thereafter. The improved retention of seeded EC on ePTFE grafts coated with FG containing FGF-1 and heparin compared to FN will need to be confirmed for longer durations of perfusion and using in vivo models.

Biointeractive polymers and tissue engineered blood vessels.

The regulation of endothelial cell (EC) and smooth muscle cell (SMC) proliferation following vascular interventions is critical to clinical efficacy. Our laboratory has developed a method of impregnating biomaterials with suspensions containing bioactive proteins resulting in the capability of differentially modulating EC and SMC growth in vitro and in vivo following implantation. We have previously reported that 60 mu internodal distance ePTFE grafts impregnated with fibrin glue (FG) containing FGF-1 and heparin develop confluent endothelialization with transiently increased EC and SMC proliferation after 4 weeks in dogs. Thoraco-abdominal implants after 20 weeks were developed significantly thicker (139 mu) inner capsules in response to the FGF. To minimize SMC proliferation we studied the effects of FGF-1, heparin, and thrombin concentrations on SMC growth in vitro. FG caused a 182% increase (P < 0.001) in DNA synthesis. Heparin within FG diminished this effect in a dose-dependant manner, with complete inhibition of FG-induced growth at 500 U ml-1 (versus FG alone, P < 0.001). FGF-1 within FG without heparin had no effect, but together, FGF-1 caused a dose-dependant growth increase while increasing heparin concentrations initially increased and then decreased proliferation. FGF-1 and heparin in the medium of quiescent SMCs had similar effects. Only thrombin concentrations > 3.2 U ml-1 stimulated SMC growth and this stimulation was blocked by heparin. A synergism between FGF and heparin on EC proliferation was also found but without EC growth inhibition in response to higher concentrations of heparin. It is thus possible to modulate the relative proliferative activity of ECs versus SMCs by altering the FGF:heparin ratio. This same system may be useful with other proteins to induce other local affects by the applied protein or systemic affects following release of that protein.

In vivo platelet deposition on polytetrafluoroethylene coated with fibrin glue containing fibroblast growth factor 1 and heparin in a canine model.

BACKGROUND: We previously reported that the coating of expanded polytetrafluoroethylene (ePTFE) with fibrin glue containing fibroblast growth factor 1 (FGF-1) and heparin accelerates endothelial coverage of grafts implanted into animals. We report here the effect of this surface modification on early platelet deposition. MATERIALS AND METHODS: Nine dogs received 7-cm ePTFE grafts, 60-microns internodal distance, 4-mm internal diameter, as bilateral aortoiliac implants, one coated (luminal cross section and abluminal surface) with fibrin glue (fibrinogen 32.1 mg/mliters, thrombin 0.32 U/mliters) containing FGF-1 (11 ng/mliters and heparin (250 U/mliters), the other uncoated. After 5, 30, or 120 minutes of circulation with blood containing autologous platelets radiolabelled with indium 111, gamma emissions were quantitated on explants and correlated to surface areas measured by computerized planimetry. RESULTS: Both global and segmental comparisons showed significantly (P < 0.05, Student's t-test) less platelet deposition on coated than on uncoated grafts after 120 minutes of circulation, but no difference at 5 and 30 minutes. CONCLUSIONS: In this model, ePTFE coating with fibrin glue containing FGF-1 and heparin shows no adverse effect on early platelet deposition.

Selective stimulation of endothelial cell proliferation with inhibition of smooth muscle cell proliferation by fibroblast growth factor-1 plus heparin delivered from fibrin glue suspensions.

BACKGROUND: Pretreatment of expanded polytetrafluoroethylene grafts with fibrin glue (FG) containing fibroblast growth factor-1 (FGF-1) (10 ng/ml) and heparin (50 units/ml) has been shown to induce a transmural angiogenesis with proliferation of both endothelial cells (ECs) and smooth muscle cells (SMCs) in dogs. To induce EC without SMC proliferation, we studied the effects of different FGF-1:heparin ratios within FG in vitro. METHODS: First passage human umbilical vein ECs (factor VIII+) or primary canine carotid artery SMCs (alpha-actin +) were seeded onto 96-well plates coated with FG containing 10 ng/ml FGF-1 and 0, 5, 50, or 500 units/ml heparin. Control wells were coated with FG without FGF-1 or heparin. Cells were fed standard growth medium without soluble FGF-1 or heparin. Tritiated thymidine (1 microCi/well) was added after 1, 2, or 3 days, and proliferation was assayed by scintillation counting 48 hours later. RESULTS: For both ECs and SMCs, proliferation on FG containing FGF-1 but no heparin was not different from control. EC proliferation on FG containing FGF-1 was significantly increased by addition of 5, 50, or 500 units/ml heparin (+68%, +99%, and +106%, respectively; p (0.0001 for all), reflecting the synergism of FGF-1 by heparin. SMC proliferation was also significantly increased by the addition of 5 or 50 units/ml heparin (+85% and +66%, respectively; p (0.0001 for both). However, SMC proliferation with 500 units/ml heparin was significantly decreased from control (-12%; p = 0.014), reflecting heparin's SMC growth inhibitory activity. CONCLUSIONS: FG containing 10 ng/ml FGF-1 and 500 units/ml heparin stimulates EC proliferation while inhibiting SMC proliferation in vitro. Application of this modified FG to vascular grafts or to arteries after direct or transcutaneous interventions may promote endothelialization without intimal hyperplasia.