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.

Implantable artificial lung. Preliminary report.

The ultimate treatment of chronic respiratory insufficiency is pulmonary replacement by an artificial organ, homologous lung transplantation, or chronic paracorporeal respiratory supplementation. The woven capillary membrane oxygenator appears to be a major development toward implantable artificial organs. The four units tested are made up of screens 3.5 by 4.0 cm. of capillary tubing 0.3 mm. I.D. by 0.64 mm. O.D. assembled into rectangular blocks. Units made up by five, ten, twenty, and forty screens have been assembled and tested according to the protocol suggested by Galletti. The maximum oxygen transfer rate with blood was 48 ml. per minute per square meter. Water carbon dioxide transfer rate was 23.1 ml. per minute per square meter. The pressure drops in the liquid phase were 8.5, 15.3, 13.8, 17.6 mm. Hg at 1 L. per minute flow. These results indicate that the woven capillary membrane lung is an acceptably efficient oxygenator. The characteristics of design and performance suggest that this oxygenator can be made to be implanted into the chest or used as a paracorporeal respiratory assistance device.

Preclotting of knitted Dacron prosthesis. A scanning electron microscope study.

A scanning electron microscope study of preclotting on knitted Dacron prosthesis is reported. Five steps of the interaction are well identified: (1) before any blood contact (virgin Dacron), (2) during the first 3 minutes (fibrin and platelet aggregates), (3) fifth minute of contact (clotting), (4) 15 minutes of contact with heparinized blood (thin fibrin network), and (5) the following minutes (invasion of fibrin, which enmeshes blood cells).

Expanded polytetrafluoroethylene arterial prostheses in humans: histopathological study of 298 surgically excised grafts.

The expanded polytetrafluoroethylene vascular prosthesis is considered to be the best synthetic alternative for peripheral arterial reconstruction. Most studies on the healing characteristics of expanded polytetrafluoroethylene prostheses have been carried out on animals, and very few data are available on prosthesis implanted in humans long term. We implanted 298 expanded polytetrafluoroethylene grafts as arterial substitutes in humans. The mean duration of implantation was 523 d and the grafts were implanted mainly for infrainguinal or axillofemoral bypass. The cellular and collagen infiltration of the microporous expanded polytetrafluoroethylene structure was generally poor. Infiltration occurred mainly in the external region of the prosthetic wall and increased with the duration of implantation. The external reinforcement was not a major factor in limiting tissue infiltration. The luminal surfaces were covered with a thin, irregular layer of organized fibrin, interspersed with exposed expanded polytetrafluoroethylene areas. Mineral deposits were observed in five cases. Despite poor healing, the clinical performance of expanded polytetrafluoroethylene vascular prostheses is relatively good. Since the chief advantage of this material is good mechanical stability in vivo, any modifications of the graft to improve healing characteristics or thrombogenic properties should not be made at the expense of stability in vivo.

Expanded polytetrafluoroethylene arterial prostheses in humans: chemical analysis of 79 explanted specimens.

The expanded polytetrafluoroethylene (ePTFE) vascular prostheses are widely used as small and medium diameter blood conduits when an autologous venous material is not available or is not suitable. The long-term performance of a prosthesis is dependent on several factors, including its healing characteristics and its stability in vivo. This study was undertaken to assess whether chemical degradation of ePTFE occurs when such arterial substitutes are implanted in humans. Seventy-nine ePTFE grafts excised for complications were analysed using the following techniques: measurement of the contact angle (theta), electron spectroscopy for chemical analysis (ESCA or XPS), Fourier transform infra-red spectroscopy (FTIR) and differential scanning calorimetry (DSC). The results were compared with those obtained from virgin ePTFE and virgin ePTFE washed prostheses. The measurement of the contact angle (theta) permits the comparison of the level of hydrophobicity of material after in vivo residency. The contact angles of explanted ePTFE grafts are greater than those of virgin ones but remain close to those of washed virgin prostheses. The ESCA method allowed investigation of the chemical changes which occur on the surface of ePTFE prostheses after implantation because of the low penetration of the X-ray (about 50 A). This study did not reveal any chemical degradation of the ePTFE with time of implantation for periods up to 6.5 yr. Changes in the surface composition were probably related to lipid and/or protein uptake. The FTIR spectroscopy provides information about the chemical composition of material. Compared with the virgin ePTFE prostheses, the FTIR spectra of explanted prostheses showed specific bands which are characteristic of lipid and/or protein absorptions. The bulk properties of ePTFE studied by DSC did not show any significant changes with time of implantation. It is concluded that ePTFE grafts remain stable in vivo for periods up to 6.5 yr.

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.

A compound arterial prosthesis: the importance of the sterilization procedure on the healing and stability of albuminated polyester grafts.

In response to the demand for a vascular prosthesis which achieves reliable haemostasis without preclotting, a new compound albumin/polyester prosthesis has been developed. In order to optimize the sterilization procedures for this device, two series of implantations in the thoracic aorta of dogs were undertaken to compare the effects of ethylene oxide (EtO) and gamma-radiation. Preclotted polyester prostheses were implanted in two additional control series. Pathological analysis of the explanted grafts indicated that gamma-radiation is to be preferred over EtO because it results in faster rates of healing. While the albumin coating delayed the thrombotic response and fibrinolytic activity, the extent of healing of the radiation sterilized graft was equivalent to that achieved by preclotted polyester prostheses in the medium and long term. Measurements of the strength and dimensional changes of the graft demonstrated that, in addition to reducing the risks of acute thrombosis and postoperative haemorrhage, the albumin coating improves the dimensional stability of the knitted structure.

Processes human umbilical veins as arterial substitutes--evaluation in canine models.

Human umbilical cord vein segments have been used as vessel substitutes for damaged or occluded arteries, as aorto-coronary by-passes and as arterio-venous fistulae for dialysis. The Dardik-Biograft fixed with glutaraldehyde and the Mindich-Bioflow, fixed with ethanol and dialdehyde starch, are commercially available. They were implanted in dogs as replacements for a segment of the abdominal aorta. Post-implantation status was followed by angiography. They were evaluated after removal from sacrificed animals with the aid of scanning electron microscopy and histological techniques. Attention was focused on vessel patency, dimensional stability, integrity of the anastomosis line, lumen wall microstructure, evidence of suture damage and thrombus deposition pattern. Both types of grafts gave functional by-passes for at least until 6 months post-implantation. The Dardik-Biograft appeared more prone to thrombus formation near the anastomosis. Sparse cellular development was also noted. The Mindich-Bioflow gave rise to a prosthesis of superior thromboresistance which was more subject to mechanical damage.

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.

Albumin coating of a knitted polyester arterial prosthesis: an alternative to preclotting.

Coating a knitted polyester arterial prosthesis with cross-linked albumin fills the interstices of the graft and relieves the surgeon of the necessity to preclot . This is of particular value in patients whose blood clotting properties are hypercoagulable, or hypocoagulable . In addition, such prostheses require less handling, which can lower the risk of bacteremic colonization and shorten the operative time. The in vivo behavior of the implanted albuminated prosthesis in the thoracic aorta of dogs is similar to that of preclotted grafts, although the sequences of early healing are different. The preclotted graft develops a continuous, thick thrombotic matrix on its luminal surface during the first 4 hours of implantation. Following the initiation of the fibrinolytic mechanism 24 to 48 hours postoperatively, this thrombotic deposit quickly recedes , leaving blood cells and platelets adhering here and there to the prosthetic surface. In comparison, the albuminated coating is not associated with major early thrombotic deposits. The albumin remains visible between the filaments during the first 2 weeks of implantation. Both treated and control grafts contain numerous thrombi on their inner surface after 1 to 2 weeks. After 1, 3, and 6 months, both implants are well encapsulated and present a glistening and continuous luminal surface. This excellent healing, however, can be compromised should the graft adhere too closely to the animal's lungs.+2

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.

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.

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.

"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.

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.

In vivo tissue distribution of fibroblast growth factor-1 after intraarterial delivery.

The clinical applicability of fibroblast growth factor-1 (FGF-1) plus heparin delivery in optimizing the healing of both autogenous vein and synthetic vascular grafts has been suggested. The authors have reported enhanced endothelial cell proliferation, concurrent increased capillarization, and minimal intimal hyperplasia using suspensions of FGF-1 and heparin impregnated onto expanded polytetrafluoroethylene grafts. The current study characterizes the tissue distribution of 125I-FGF-1 delivered by continuous intraarterial infusion. 125I-FGF-1 delivered by continuous intraarterial infusion. 125I-FGF-1 (1.1 ng) and heparin (28 U) were continuously infused into the thoracic aorta via the proximal end of the ligated left carotid artery for 24 hr in four New Zealand white rabbits using an Alzet (Alza Corp., Palo Alto, CA) osmotically activated pumping device. Rabbits were sacrificed after 24 hr, exsanguinated, and biopsies taken from the liver, kidneys, spleen, lungs, heart, thyroid gland, muscle, and fat. These samples were assayed for radioactivity and results expressed as cpm 125I/gram of both wet and dry weight of tissue. 125I-FGF-1 uptake (cpm/g dry wt.) was greatest in the thyroid (551.1 +/- 131.4). This was 2.5-5.5 x greater (p < or = 0.01) than those organs with intermediate uptake (lungs, liver, kidneys, spleen, and heart). Lowest uptake was noted in the blood, muscle, and fat. A similar distribution pattern was found in wet weight comparisons. Total organ 125I-FGF-1 content was greatest in the liver at 818.1 +/- 176.3 cpm (p < or = 0.002) and intermediate in the lungs (204.7 +/- 38.5 cpm) and kidneys (191.2 +/- 11.9 cpm). Although no FGF-1-induced toxicity has yet been reported, these results will allow for future tissue-specific toxicology studies before clinical trials.

A pathological study of arterial prostheses surgically excised after overt clinical infection.

Infection caused regarding vascular grafts in vascular surgery still remains a major problem. To reduce this problem and the complications which follow, the surgeon must be able to apply the best surgical management and also be confident with the vascular substitute used. There are two important factors to be considered: the biomaterial must have low propensity to infection and good stability if and when infected. In an attempt to verify this problem, 93 vascular grafts surgically excised for overt infection were examined. Techniques used for examinations were gross morphology, histopathology and scanning electron microscopy (SEM) evaluation. There were 23 human umbilical vein (HUV) grafts, 51 Dacron grafts and 19 expanded polytetrafluoroethylene (ePTFE) grafts. Histopathological signs of infection were absent in 57% of the ePTFE and Dacron grafts and in 17.4% of the HUV grafts. The latter were more heavily histologically infected and in some cases the walls were destructed. Histopathological signs of infection were seen on all the prosthetic walls in 36% of all the specimens and were mainly on the external portion of the grafts for the remaining prostheses. Bacteria were seen in respectively 21.7, 15.7 and 20% of the HUV, Dacron and ePTFE grafts with the Gram stain and in 86.9, 84.3 and 94.7% with SEM. The implantation period was shorter for the bioprostheses compared to that of the synthetic grafts because of the site and the indication of implantation. The stability of the bioprostheses was lower compared to that of the synthetic grafts when infected, leading to a breakdown of the wall along the length of the graft. The infection was found on the external capsule of the grafts rather than on the luminal surface.

New frontiers of vascular grafting.

Vascular grafting can be a very rewarding surgical technique: following surgery, most patients will maintain their autonomy and, in many cases, will be able to return to work. Should small diameter calibre substitutes be required, the autologous saphenous vein is the gold standard. If not available, the expanded PTFE is probably the best choice. For medium and large diameters, the polyesters (Dacron) are recommended provided they have a structure adapted to the needs of patients. However, progress in the last few years is not related to improvements in the grafts themselves. The only breakthrough has come with the success of graft seeding. This is the reason why other approaches have been proposed to restore or improve blood flow in atherosclerotic arteries: medication, sympathectomy, dilatation, laser endarterectomy, stent and spinal cord stimulation. All those approaches have more and more precise indications: they can supplement vascular grafting.

[Fibrous hyperplasia in femoro-popliteal bypasses using treated human umbilical veins]. / Hyperplasies fibreuses sur pontages fémoro-poplités par veines ombilicales humaines traitées.

The authors report two clinical cases of the failure due to fibrous hyperplasia of processed human umbilical vein (HUV) grafts employed as femoro-popliteal bypasses. Failure occurred after 19 months implantation at the proximal anastomosis for one graft and after 10 months at the distal anastomosis for the other. Fibrous hyperplasia was the principal cause of reoperation. The lightly vascularized, more or less compacted fibrin involved, adhering loosely to the HUV, remains thrombogenic at the blood-contacting surface. Superposed onto this phenomenon which is widespread in laboratory animals but uncommon in humans, are the usual causes of failure: delamination of the HUV wall, lipid uptake and bacterial colonization.