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.

Entanglement dynamics in the presence of controlled unital noise.

Quantum entanglement is notorious for being a very fragile resource. Significant efforts have been put into the study of entanglement degradation in the presence of a realistic noisy environment. Here, we present a theoretical and an experimental study of the decoherence properties of entangled pairs of qubits. The entanglement dynamics of maximally entangled qubit pairs is shown to be related in a simple way to the noise representation in the Bloch sphere picture. We derive the entanglement level in the case when both qubits of a Bell state are transmitted through any arbitrary unital Pauli channel, and compare it to the case when the channel is applied only to one of the qubits. The dynamics of both cases was verified experimentally using an all-optical setup. We further investigated the evolution of partially entangled initial states. Different dynamics was observed for initial mixed and pure states of the same entanglement level.

Entanglement swapping between photons that have never coexisted.

The role of the timing and order of quantum measurements is not just a fundamental question of quantum mechanics, but also a puzzling one. Any part of a quantum system that has finished evolving can be measured immediately or saved for later, without affecting the final results, regardless of the continued evolution of the rest of the system. In addition, the nonlocality of quantum mechanics, as manifested by entanglement, does not apply only to particles with spacelike separation, but also to particles with timelike separation. In order to demonstrate these principles, we generated and fully characterized an entangled pair of photons that have never coexisted. Using entanglement swapping between two temporally separated photon pairs, we entangle one photon from the first pair with another photon from the second pair. The first photon was detected even before the other was created. The observed two-photon state demonstrates that entanglement can be shared between timelike separated quantum systems.

Compact 2D nonlinear photonic crystal source of beamlike path entangled photons.

We demonstrate a method to generate entangled photons with controlled spatial shape by parametric down conversion (PDC) in a 2D nonlinear crystal. A compact and novel crystal source was designed and fabricated, generating directly path entangled photons without the use of additional beam-splitters. This crystal supports two PDC processes, emitting biphotons into two beamlike modes simultaneously. Two coherent path entangled amplitudes of biphotons were created and their interference observed. Our method enables the generation of entangled photons with controlled spatial, spectral and polarization properties.

Resource efficient source of multiphoton polarization entanglement.

Current photon entangling schemes require resources that grow with the photon number. We present a new approach that generates quantum entanglement between many photons, using only a single source of entangled photon pairs. The different spatial modes, one for each photon as required by other schemes, are replaced by different time slots of only two spatial modes. States of any number of photons are generated with the same setup, solving the scalability problem caused by the previous need for extra resources. Consequently, entangled photon states of larger numbers than before are practically realizable.

The biaxial nonlinear crystal BiB3O6 as a polarization entangled photon source using non-collinear type-II parametric down-conversion.

We describe the full characterization of the biaxial nonlinear crystal BiB3O6 (BiBO) as a polarization entangled photon source using non-collinear type-II parametric down-conversion. We consider the relevant parameters for crystal design, such as cutting angles, polarization of the photons, effective nonlinearity, spatial and temporal walk-offs, crystal thickness and the effect of the pump laser bandwidth. Experimental results showing entanglement generation with high rates and a comparison to the well investigated ß-BaB2O4 (BBO) crystal are presented as well. Changing the down-conversion crystal of a polarization entangled photon source from BBO to BiBO enhances the generation rate as if the pump power was increased by 2.5 times. Such an improvement is currently required for the generation of multiphoton entangled states.

Projection of two biphoton qutrits onto a maximally entangled state.

Bell state measurements, in which two quantum bits are projected onto a maximally entangled state, are an essential component of quantum information science. We propose and experimentally demonstrate the projection of two quantum systems with three states (qutrits) onto a generalized maximally entangled state. Each qutrit is represented by the polarization of a pair of indistinguishable photons-a biphoton. The projection is a joint measurement on both biphotons using standard linear optics elements. This demonstration enables the realization of quantum information protocols with qutrits, such as teleportation and entanglement swapping.

Mifepristone (RU486), a pure antiprogesterone drug, in combination with vinblastine for the treatment of progesterone receptor-positive desmoid tumor.

We report the case of a patient who developed a desmoid tumor following total proctocolectomy and J-pouch reconstruction that was unresponsive to any medical treatment. Based on estrogen receptor alpha (ERalpha) and progesterone receptor (PR) evaluation (ERalpha-negative, but PR-positive), treatment with mifepristone, a pure antiprogesterone drug, was initiated, and partial tumor regression was achieved.

En bloc resection for malignant colouterine fistula.

Colouterine fistula is a rare clinical entity. A literature search revealed only a few reports dealing with this complex problem, mostly resulting as a complication of diverticular disease of the colon. During a 4-month period, we diagnosed and successfully treated 2 women with a malignant colouterine fistula originating from a primary colorectal carcinoma invading the uterus. We herein report on our experience dealing with this kind of pathology, with special emphasis on the surgical technique used to resect the tumoral mass "en bloc".

The possible association between IVF and breast cancer incidence.

BACKGROUND: The possible association between ovulation-inducing drugs and breast cancer development has been debated. Our aim was to evaluate the incidence of breast cancer in a cohort of women exposed to in vitro fertilization (IVF). METHODS: A retrospective cohort analysis was performed by linkage of the computerized database of all women treated at the IVF Unit at Assaf Harofeh Medical Center between 1986 and 2003, and the Israeli National Cancer Registry. The standardized incidence ratio (SIR) was computed as the ratio between the observed number of breast cancer cases and the expected cases, adjusted for age and continent of birth, in the general population. Tumor characteristics of the IVF patients were studied by reviewing original medical records. RESULTS: 35 breast carcinomas were diagnosed among 3,375 IVF-treated women, compared to 24.8 cases expected (SIR = 1.4; 95% CI 0.98-1.96). Age >or=40 years at IVF treatment (SIR = 1.9; 95% CI 0.97-3.30), hormonal infertility (SIR = 3.1; 95% CI 0.99-7.22), and >or=4 IVF cycles (SIR = 2.0; 95% CI 1.15-3.27) were found to be risk factors to develop breast cancer compared to the general population. Multivariate analysis revealed that women who underwent >or=4 IVF cycles compared to those with one to three cycles were at risk to develop breast cancer, although not significantly (SIR = 1.9; 95% CI 0.95-3.81). Of IVF-treated women 85% had ER(+) tumors and 29% had positive family history. CONCLUSIONS: A possible association between IVF therapy and breast cancer development was demonstrated, especially in women >or=40 years of age. These preliminary findings need to be replicated in other cohort studies.

Early detection of life-threatening intracranial haemorrhage using a portable near-infrared spectroscopy device.

OBJECTIVE: To determine whether infrared spectroscopy allows early recognition of epidural and subdural haematomas among trauma patients. METHODS: Injured people admitted to two trauma units were enrolled in a prospective multicentre observational study, and infrared spectroscopy was performed before computed tomography of the head as a part of their initial evaluation. Subsequent CT findings suggestive of epidural or subdural haematoma served as controls. RESULTS: Over 12 months, 110 patients were enrolled; 64 (58.1%) were men and 46 (41.9%) were women. Mean age was 56.2 years, and mean Glasgow Coma Scale on admission was 12.6. Infrared spectroscopy was 90.5% sensitive and 95.5% specific for epidural and subdural haematoma. Positive and negative predictive values were 82.6% and 97.7%, respectively. CONCLUSIONS: Infrared spectroscopy allows early recognition of epidural and subdural haematomas in trauma cases. Further studies are needed to evaluate whether immediate confirmation or exclusion of epidural and subdural haematomas with portable near-infrared spectroscopy devices improves the decision-making process in the treatment of severely injured people.

Breast cancer in the elderly: histological, hormonal and surgical characteristics.

The characteristics, menstrual risk factors and surgical therapy of 187 consecutive patients more than 70 years of age (mean: 75.9) were investigated and compared with those of 609 patients less than 70 years of age (mean: 53.9). There was no difference in stage, size, state of axillary nodes, grade, histological types, Ki-67, vascular invasion, estrogen receptor rate, and HER-2/neu (+) rate. Positive progesterone receptor rate was higher in older patients (54.7% vs. 63.1%). Tumors were larger (p=0.01) and their stage higher (p=0.014) in patients more than 80 years of age. All menstrual risk factors were similar in the two groups. Positive familial history was more frequent in patients <60 years. Significantly more young patients used hormone replacement therapy (HRT) (21.8 vs. 8.6%). Older patients underwent less breast-conserving surgery (36.1 vs. 55.1%), and less axillary lymph node dissection (ALND) (69.7 vs. 84.9%). We conclude that breast cancer characteristics and menstrual risk factors are similar in the two age groups.

Anal melanoma in the era of sentinel lymph node mapping: a diagnostic and therapeutic challenge.

Melanoma of the anal canal is a rare malignancy that often has an atypical presentation. Locoregional metastases, which are often present at the initial presentation, may occur in both groin and pelvic lymph nodes, but the utility of lymph node dissection remains unknown. We explored the possibility of applying the technique of sentinel lymph node (SLN) mapping to anal melanoma. SLN mapping was performed in 2 patients with anal melanoma. Radioactive tracer and blue dye were injected around the lesions. The SLN was identified pre-operatively by lymphoscintigraphy, and at surgery with a hand-held gamma detector and by visualization of the dye. The SLN was identified in both patients, only in the groin in one and only in the presacral region in the other. One patient had a wide local excision of the anal lesion with house flap anoplasty, while the other had abdominoperineal resection with total mesorectal excision. There were no SLN metastases in either patient. The technique of SLN mapping and biopsy is easily adapted to surgery for malignant melanoma of the anus. SLN mapping and biopsy could aid in planning surgical strategy, but definitive conclusions may only be reached after more experience has been acquired.

PQL: a declarative query language over dynamic biological schemata.

We introduce the PQL query language (PQL) used in the GeneSeek genetic data integration project. PQL incorporates many features of query languages for semi-structured data. To this we add the ability to express metadata constraints like intended semantics and database curation approach. These constraints guide the dynamic generation of potential query plans. This allows a single query to remain relevant even in the presence of source and mediated schemas that are continually evolving, as is often the case in data integration.

Gravitropism in cut flower stalks of snapdragon.

The negative gravitropic response of cut flower stalks is a complex multistep process that requires the participation of various cellular components acting in succession or in parallel. The process was particularly characterized in snapdragon (Antirrhinum majus L.) spikes with regard to (1) gravity stimulus perception associated with amyloplast reorientation; (2) stimulus transduction mediated through differential changes in the level, action and related genes of auxin and ethylene and their possible interaction; (3) stimulus response associated with differential growth leading to stalk curvature; (4) involvement of cytosolic calcium and actin cytoskeleton. Results show that the gravity-induced amyloplast reorientation, differential over-expression of two early auxin responsive genes and asymmetrical distribution of free IAA are early events in the bending process. These precede the asymmetrical ethylene production and differential stem growth, which was derived from initial shrinkage of the upper stem side and a subsequent elongation of the lower stem side. Results obtained with various calcium- and cytoskeleton-related agents indicate that cytosolic calcium and actin filaments may play essential roles in gravitropism-related processes of cut flower stalks. Therefore, modulators of these two physiological mediators may serve as means for controlling any undesired gravitropic bending.

[Quick intraoperative parathormone monitoring].

Successful parathyroidectomy for primary hyperparathyroidism has traditionally consisted of bilateral neck exploration with identification of all parathyroid glands and excision of grossly abnormal glands. Recently it has been reported that preoperative localization combined with intraoperative monitoring of parathyroid hormone enables performing directed unilateral cervical explorations while maintaining similar cure rates. This new surgical approach, feasible under local anesthesia as an outpatient procedure, decreases operative time, improves cosmetic results and may reduce morbidity. We report preliminary results of our experience in implementing this method.

Effect of electrocautery vs. scalpel on fascial mechanical properties after midline laparotomy incision in rats.

BACKGROUND: The method of midline laparotomy incision and closure remains a complex surgical problem. OBJECTIVE: To compare the mechanical properties at the interface of midline laparotomy incision made by scalpel versus electrocuting current in rats. METHODS: A sharp midline laparotomy incision was made in 60 Wistar female rats using a scalpel or electrocautery to open the fascia. The fascial and skin wounds were closed separately with a continuous nylon. Fascial specimens were analyzed for mechanical properties at the midline incision using a loading machine. The load-extension curve was recorded during tensile loading at a steady extension rate of 15 mm/min. RESULTS: There was no statistically significant difference between the two groups in either wound-bursting force (PPEAK) or the strain energy spent until the point of measured PPEAK. Each load-extension curve showed a characteristic pattern in all rats. Tissue stiffness was greater in the scalpel group than in the electrocautery group (P = 0.02). Correlations were found between tissue stiffness and strain energy, between tissue stiffness and bursting force, and between bursting force and strain energy. CONCLUSIONS: While tissue stiffness was greater when a scalpel was used compared to electrocuting to incise the midline abdominal fascia in rats, there was no difference in the bursting force required to disrupt the wound.

[Primary gastrointestinal stromal tumors].

UNLABELLED: Stromal tumors of the GI tract are rare. In the retrospective and prospective study we investigated the relationship between tumor symptomatology, tumor grade and prognostic factors. During the period May 1993-September 1999, 11 female and 13 male patients with a mean age of 62 (range-29-81) years were operated for primary gastrointestinal stomal tumors (GIST) in our department. Observed signs and symptoms were: GI bleeding (65%), abdominal pain (45%), abdominal mass (15%) and weakness (5%). In 4 patients tumor was an incidental finding during investigation or operation for another tumor. Tumor location (in decreasing order) was: stomach (15), small bowel (SB, 6), esophagus (1), duodenum (1) and colon (1). Preoperative biopsy or FNA were diagnostic in less than 50% of the cases. Operative procedures included wedge resection (8 patients), resection of segment of bowel (10) and extended resection (6), of diaphragm, SB, colon, bladder, kidney and liver. The mean tumor size was 7.8 (range-0.9-22) cm. Four tumors were graded as benign, 8 of indeterminate malignant potential and 12 malignant. CONCLUSION: The main presentation of GIST is acute GI bleeding. Endoscopy is most effective for studying proximal tumors, and CT should be used to identify distal GI tract tumors. Tumor size or malignancy were not necessarily predictive of GI bleeding. When invasive to adjacent organs is present, wide excision should be contemplated as long-term survival can be achieved.