Differential phase-shift-keying demodulation by coherent perfect absorption in silicon photonics.

We demonstrate a novel differential phase-shift-keying (DPSK) demodulator based on coherent perfect absorption (CPA). Our DPSK demodulator chip device, which incorporates a silicon ring resonator, two bus waveguide inputs, and monolithically integrated detectors, operates passively at a bit rate of 10 Gbps at telecommunication wavelengths, and fits within a mm-scale footprint. Critical coupling is used to achieve efficient CPA by tuning the gap between the ring and bus waveguides. The device has a vertical eye opening of 12.47 mV and a quality factor exceeding 3×104. The fundamental principle behind this photonic circuit can be extended to other formats of integrated demodulators.

Mental health outcomes after major trauma in Ontario: a population-based analysis.

BACKGROUND: Major injury continues to be a common source of morbidity and mortality; improving the functional recovery of survivors of major trauma requires a better understanding of the mental health outcomes that may occur in this population. We assessed the association between major trauma and the development of a new mental health diagnosis or death by suicide. METHODS: We completed a population-based, self-controlled, longitudinal cohort analysis using linked administrative data on patients treated for major trauma in Ontario between 2005 and 2010. All survivors were included and composite rates of mental health diagnoses during inpatient admissions were compared between the 5 years after injury and the 5 years before injury, using Poisson regression with generalized estimating equations. The incidence of suicide was calculated for the 5 years after injury. Risk factors for suicide were calculated using Cox proportional hazard regression analyses. RESULTS: The analysis included 19 338 patients, predominantly men (70.7%) from urban areas (82.6%), with unintentional (89%), blunt injuries (93.4%). Overall, trauma was associated with a 40% increase in the postinjury rate of mental health diagnoses (incidence rate ratio [IRR] 1.4, 95% [confidence interval] CI 1.1 to 1.8). The suicide rate was 70 per 100 000 patients per year, substantially higher than the population average. Risk factors for completing suicide were prior inpatient diagnosis of mood disorder (hazard ratio [HR] 4.3, 95% CI 2.1 to 8.8) and self-inflicted injury (HR 7.8, 95% CI 3.9 to 15.4). INTERPRETATION: Survivors of major trauma are at a heightened risk of developing mental health conditions or death by suicide in the years after their injury. Patients with pre-existing mental health disorders or who are recovering from a self-inflicted injury are at particularly high risk.

Efficient photon triplet generation in integrated nanophotonic waveguides.

Generation of entangled photons in nonlinear media constitutes a basic building block of modern photonic quantum technology. Current optical materials are severely limited in their ability to produce three or more entangled photons in a single event due to weak nonlinearities and challenges achieving phase-matching. We use integrated nanophotonics to enhance nonlinear interactions and develop protocols to design multimode waveguides that enable sustained phase-matching for third-order spontaneous parametric down-conversion (TOSPDC). We predict a generation efficiency of 0.13 triplets/s/mW of pump power in TiO2-based integrated waveguides, an order of magnitude higher than previous theoretical and experimental demonstrations. We experimentally verify our device design methods in TiO2 waveguides using third-harmonic generation (THG), the reverse process of TOSPDC that is subject to the same phase-matching constraints. We finally discuss the effect of finite detector bandwidth and photon losses on the energy-time coherence properties of the expected TOSPDC source.

Low-loss titanium dioxide waveguides and resonators using a dielectric lift-off fabrication process.

We present a bi-layer lift-off fabrication approach to create low-loss amorphous titanium dioxide (TiO2) integrated optical waveguides and resonators for visible and near-infrared applications. This approach achieves single-mode waveguide losses as low as 7.5 dB/cm around 633 nm and 1.2 dB/cm around 1550 nm, a factor of 4 improvement over previous reports, without the need to optimize etching conditions. Depositing a secondary 260-nm TiO2 layer can reduce losses further, with the optimized process yielding micro-ring resonators with loaded quality factors as high as 1.5 × 10(5) around 1550 nm and 1.6×10(5) around 780 nm. These losses render our TiO2 devices suitable for visible and telecommunications applications; in addition, the simplicity of this lift-off approach is broadly applicable to other novel material platforms, particularly using near-visible wavelengths.

Multimode phase-matched third-harmonic generation in sub-micrometer-wide anatase TiO2 waveguides.

Third-harmonic generation (THG) has applications ranging from wavelength conversion to pulse characterization, and has important implications for quantum sources of entangled photons. However, on-chip THG devices are nearly unexplored because bulk techniques are difficult to adapt to integrated photonic circuits. Using sub-micrometer-wide polycrystalline anatase TiO2 waveguides, we demonstrate third-harmonic generation on a CMOS-compatible platform. We correlate higher conversion efficiencies with phase-matching between the fundamental pump mode and higher-order signal modes. Using scattered light, we estimate conversion efficiencies as high as 2.5% using femtosecond pulses, and thus demonstrate that multimode TiO2 waveguides are promising for wideband wavelength conversion and new applications ranging from sensors to triplet-photon sources.

The emergence of macrocyclic lactone resistance in the canine heartworm, Dirofilaria immitis.

Prevention of heartworm disease caused by Dirofilaria immitis in domestic dogs and cats relies on a single drug class, the macrocyclic lactones (MLs). Recently, it has been demonstrated that ML-resistant D. immitis are circulating in the Mississippi Delta region of the USA, but the prevalence and impact of these resistant parasites remains unknown. We review published studies that demonstrated resistance in D.immitis, along with our current understanding of its mechanisms. Efforts to develop in vitro tests for resistance have not yet yielded a suitable assay, so testing infected animals for microfilariae that persist in the face of ML treatment may be the best current option. Since the vast majority of D. immitis populations continue to be drug-sensitive, protected dogs are likely to be infected with only a few parasites and experience relatively mild disease. In cats, infection with small numbers of worms can cause severe disease and so the clinical consequences of drug resistance may be more severe. Since melarsomine dihydrochloride, the drug used to remove adult worms, is not an ML, the ML-resistance should have no impact on our ability to treat diseased animals. A large refugium of heartworms that are not exposed to drugs exists in unprotected dogs and in wild canids, which may limit the development and spread of resistance alleles.

Concurrent transcriptional profiling of Dirofilaria immitis and its Wolbachia endosymbiont throughout the nematode life cycle reveals coordinated gene expression.

BACKGROUND: Dirofilaria immitis, or canine heartworm, is a filarial nematode parasite that infects dogs and other mammals worldwide. Current disease control relies on regular administration of anthelmintic preventives, however, relatively poor compliance and evidence of developing drug resistance could warrant alternative measures against D. immitis and related human filarial infections be taken. As with many other filarial nematodes, D. immitis contains Wolbachia, an obligate bacterial endosymbiont thought to be involved in providing certain critical metabolites to the nematode. Correlations between nematode and Wolbachia transcriptomes during development have not been examined. Therefore, we detailed the developmental transcriptome of both D. immitis and its Wolbachia (wDi) in order to gain a better understanding of parasite-endosymbiont interactions throughout the nematode life cycle. RESULTS: Over 215 million single-end 50 bp reads were generated from total RNA from D. immitis adult males and females, microfilariae (mf) and third and fourth-stage larvae (L3 and L4). We critically evaluated the transcriptomes of the various life cycle stages to reveal sex-biased transcriptional patterns, as well as transcriptional differences between larval stages that may be involved in larval maturation. Hierarchical clustering revealed both D. immitis and wDi transcriptional activity in the L3 stage is clearly distinct from other life cycle stages. Interestingly, a large proportion of both D. immitis and wDi genes display microfilarial-biased transcriptional patterns. Concurrent transcriptome sequencing identified potential molecular interactions between parasite and endosymbiont that are more prominent during certain life cycle stages. In support of metabolite provisioning between filarial nematodes and Wolbachia, the synthesis of the critical metabolite, heme, by wDi appears to be synchronized in a stage-specific manner (mf-specific) with the production of heme-binding proteins in D. immitis. CONCLUSIONS: Our integrated transcriptomic study has highlighted interesting correlations between Wolbachia and D. immitis transcription throughout the life cycle and provided a resource that may be used for the development of novel intervention strategies, not only for the treatment and prevention of D. immitis infections, but of other closely related human parasites as well.

Health service use in major trauma survivors: a population-based cohort study from Ontario, Canada.

BACKGROUND: Little is known about how major trauma survivors access health services in the years following their injury. Our study sought to characterize patterns of health services use in trauma survivors following discharge from a provincial trauma centre and to identify sociodemographic factors associated with service utilization. METHODS: We conducted a population-based retrospective case-control study using linked administrative data on trauma survivors' population-based controls between April 1, 2011, to March 31, 2021. For each major trauma survivor, we matched four cases based on age and sex. The primary outcome was the composite rate (sum) of health service use episodes including outpatient visits to family physicians and specialists, emergency department (ED) visits, and acute care hospital admissions during the five-year period following discharge from the trauma centre. We used multivariate regression to compute rate ratios comparing the rates of health service use in trauma survivors versus controls and to assess for associations between sociodemographic variables and health services use. RESULTS: The study cohort consisted of a total of 273,406 individuals: 55,060 trauma survivors and 218,346 controls. Trauma survivors were predominately males (71%) with a median age of 46 years (IQR: 26-65 years). Health service use in trauma survivors peaked within a year of hospital discharge but remained increased throughout the follow up period. Trauma survivorship was associated with a 56% increase in overall health services use (Adjusted Rate Ratio 1.56, 95% CI: 1.55-1.57), including an 88% increase in hospital admissions (Adjusted Rate Ratio 1.88, 95% CI: 1.85-1.92). Male sex and rural residence were associated with a reduced overall use of health services but greater use of ED services. CONCLUSION: Major trauma survivors have long-term health services needs that persist for years after discharge from the trauma centre. Future research should focus on the understanding why trauma survivors have prolonged health services requirements and ensure care needs are aligned with service delivery. LEVEL OF EVIDENCE: Retrospective cohort study, Level IV.

Spectral broadening in anatase titanium dioxide waveguides at telecommunication and near-visible wavelengths.

We observe spectral broadening of femtosecond pulses in single-mode anatase-titanium dioxide (TiO(2)) waveguides at telecommunication and near-visible wavelengths (1565 and 794 nm). By fitting our data to nonlinear pulse propagation simulations, we quantify nonlinear optical parameters around 1565 nm. Our fitting yields a nonlinear refractive index of 0.16 × 10(-18) m(2)/W, no two-photon absorption, and stimulated Raman scattering from the 144 cm(-1) Raman line of anatase with a gain coefficient of 6.6 × 10(-12) m/W. Additionally, we report on asymmetric spectral broadening around 794 nm. The wide wavelength applicability and negligible two-photon absorption of TiO(2) make it a promising material for integrated photonics.

Effects of doxycycline dose rate and pre-adulticide wait period on heartworm-associated pathology and adult worm mass.

BACKGROUND: The American Heartworm Society canine guidelines recommend treatment with doxycycline prior to adulticide administration to reduce levels of Wolbachia and its associated metabolites, which are known to be a leading cause of pulmonary pathology. Studies have determined that doxycycline administered at 10 mg/kg BID for 28 days is an effective dose for eliminating Wolbachia, but what has not been determined is the clinical relevance of this elimination. The current guidelines also recommend a 30-day wait period following administration of doxycycline to allow for clearance of metabolites, such as Wolbachia surface protein, and for further reduction in heartworm biomass before administration of adulticide. Reducing the doxycycline dose and eliminating the wait period may carry practical benefits for the animal, client, and practitioner. METHODS: To investigate these treatment practices, Dirofilaria immitis adults were surgically transplanted into each of 45 dogs, which were divided into nine study groups of five dogs each. Seventy-five days after transplantation, two groups each were administered 5, 7.5, or 10 mg/kg BID doxycycline orally for 28 days and 6 µg/kg ivermectin monthly, with three untreated groups serving as controls. Study animals were necropsied and examined prior to treatment as well as 30 and 60 days post-treatment. RESULTS: Mean worm weight was unaffected by dosage but exhibited a significant increase at 30 days and significant decrease at 60 days post-treatment, including in control groups. Histopathology lesion scores did not significantly differ among groups, with the exception of the lung composite score for one untreated group. Liver enzymes, the levels of which are a concern in doxycycline treatment, were also examined, with no abnormalities in alanine aminotransferase or alkaline phosphatase observed. CONCLUSIONS: No consistent worsening of tissue lesions was observed with or without the AHS-recommended 30-day wait period, nor did reduced dosages of doxycycline lead to worsening of pathology or any change in efficacy in depleting worm weight. Mean worm weight did significantly increase prior to, and decrease following, the wait period. Future work that also includes adulticide treatment (i.e. melarsomine) will study treatment recommendations that may improve both animal health and owner compliance.

Mixed two- and three-photon absorption in bulk rutile (TiO2) around 800 nm.

We observe mixed two- and three-photon absorption in bulk rutile (TiO2) around 800 nm using the open aperture Z-scan technique. We fit the data with an extended model that includes multiphoton absorption, beam quality, and ellipticity. The extracted two- and three-photon absorption coefficients are below 1 mm/GW and 2 mm3/GW2, respectively. We observe negligible two-photon absorption for 813-nm light polarized along the extraordinary axis. We measure the nonlinear index of refraction and obtain two-photon nonlinear figures of merit greater than 1.1 at 774 nm and greater than 12 at 813 nm. Similarly, we obtain three-photon figures of merit that allow operational intensities up to 0.57 GW/mm2. We conclude that rutile is a promising material for all-optical switching applications around 800 nm.

Submicrometer-wide amorphous and polycrystalline anatase TiO2 waveguides for microphotonic devices.

We demonstrate amorphous and polycrystalline anatase TiO(2) thin films and submicrometer-wide waveguides with promising optical properties for microphotonic devices. We deposit both amorphous and polycrystalline anatase TiO(2) using reactive sputtering and define waveguides using electron-beam lithography and reactive ion etching. For the amorphous TiO(2), we obtain propagation losses of 0.12 ± 0.02 dB/mm at 633 nm and 0.04 ± 0.01 dB/mm at 1550 nm in thin films and 2.6 ± 0.5 dB/mm at 633 nm and 0.4 ± 0.2 dB/mm at 1550 nm in waveguides. Using single-mode amorphous TiO(2) waveguides, we characterize microphotonic features including microbends and optical couplers. We show transmission of 780-nm light through microbends having radii down to 2 µm and variable signal splitting in microphotonic couplers with coupling lengths of 10 µm.

Integrated TiO2 resonators for visible photonics.

We demonstrate waveguide-coupled titanium dioxide (TiO(2) racetrack resonators with loaded quality factors of 2.2×10(4) for the visible wavelengths. The structures were fabricated in sputtered TiO(2) thin films on oxidized silicon substrates using standard top-down nanofabrication techniques, and passively probed in transmission measurements using a tunable red laser.

Longer-term rates of survival and reintervention after thoracic endovascular aortic repair (TEVAR) for blunt aortic injury: a retrospective population-based cohort study from Ontario, Canada.

Objectives: Blunt aortic injury (BAI) is associated with a high rate of mortality. Thoracic endovascular aortic repair (TEVAR) has emerged as the preferred treatment option for patients with BAI. In this study, we compare the longer-term outcomes of patients receiving TEVAR with other treatment options for BAI. Methods: We conducted a retrospective cohort study using administrative health data on patients with BAI in Ontario, Canada between 2009 and 2020. Patients with BAI and who survived at least 24 hours after hospital admission were identified using diagnostic codes. We classified patients as having received TEVAR, open surgical, hybrid repair, or medical management as their initial treatment approach based on procedure codes. The primary outcome was survival to maximum follow-up. Secondary outcomes included aorta-related mortality or aortic reintervention. Cox's proportional hazards models were used to estimate the effect of TEVAR on survival. Results: 427 patients with BAI were followed for a median of 3 years (IQR: 1-6 years), with 348 patients (81.5%) surviving. Survival to maximum follow-up did not differ between treatment groups: TEVAR: 79%, surgical repair: 63.6%, hybrid repair: 85.7%, medical management: 83.3% (p=0.10). In adjusted analyses, TEVAR was not associated with improved survival compared with surgical repair (HR: 0.6, 95% CI: 0.3 to 1.6), hybrid repair (HR: 1.4, 95% CI: 0.5 to 3.6), or medical management (HR: 1.5, 95% CI: 0.8 to 2.6). Aortic reinterventions were required in only 2.6% of surviving patients but were significantly more common in the TEVAR group (p<0.01). Conclusions: The longer-term survival from BAI appears highly favorable with low rates of reintervention and death in the years after injury, regardless of the initial treatment approach. Level of evidence: IV, Therapeutic study.

Emergency department return visits and hospital admissions in trauma team assessed patients initially discharged from the emergency department: A population-based cohort study.

BACKGROUND: Many injured patients are transported directly to trauma centers, found to be minimally injured, and discharged directly home from the emergency department (ED). Our objectives were to characterize the short-term outcomes in this discharged patient population and to identify patient factors predictive of ED return visits. METHODS: We conducted a retrospective population-based cohort study using linked administrative data sets involving patients assessed at trauma centers in Ontario, Canada between April 1, 2009, and March 31, 2020. Patients who were assessed by a trauma team and discharged directly home from ED were included. The primary outcome was the percentage of patients with an ED return visit within 14 days. We used multivariate logistic regression analyses to identify patient characteristics predictive of at least one ED return visit. RESULTS: There were 5,550 patients included in the study. A total of 1,004 (18.1%) of patients had at least one ED return visit, but only 100 patients (1.8%) were admitted to hospital following initial discharge. Common reasons for ED return visits included wound care concerns (17.2%), head injury complaints (15.6%), and substance misuse (6.8%). Rural residence (odds ratio [OR], 1.83; 95% CI, 1.45-2.29), history of anxiety disorder (OR, 2.05; 95% CI, 1.54-2.73), high baseline ED usage (OR, 2.58; 95% CI, 2.03-3.28), penetrating injury (OR, 1.42; 95% CI, 1.20-1.68), and extremity fracture (OR, 1.52; 95% CI, 1.24-1.88) predicted return visits. CONCLUSION: Patients discharged directly have high rates of ED return visits but low rates of hospital admission or delayed surgical intervention. Trauma services should expand quality assurance initiatives to capture return visits, understand any gaps in clinical service provision, and aim to minimize unnecessary ED return visits. LEVEL OF EVIDENCE: Prognostic/Epidemiological; Level IV.

The Domestic Dog as a Laboratory Host for Brugia malayi.

Of the three nematodes responsible for lymphatic filariasis in humans, only Brugia malayi is actively maintained in research settings owing to its viability in small animal hosts, principal among which is the domestic cat. While the microfilaremic feline host is necessary for propagation of parasites on any significant scale, this system is plagued by a number of challenges not as pronounced in canine filarial models. For this reason, we investigated the capacity in which dogs may serve as competent laboratory hosts for B. malayi. We infected a total of 20 dogs by subcutaneous injection of 500 B. malayi third-stage larvae (L3) in either a single (n = 10) or repeated infection events (125 L3 per week for four weeks; n = 10). Within each group, half of the individuals were injected in the inguinal region and half in the dorsum of the hind paw. To track the course of microfilaremia in this host, blood samples were examined by microscopy biweekly for two years following infection. Additionally, to identify cellular responses with potential value as predictors of patency, we measured peripheral blood leukocyte counts for the first year of infection. A total of 10 of 20 dogs developed detectable microfilaremia. Peak microfilaria density varied but attained levels useful for parasite propagation (median = 1933 mL-1; range: 33-9950 mL-1). Nine of these dogs remained patent at 104 weeks. A two-way ANOVA revealed no significant differences between infection groups in lifetime microfilaria production (p = 0.42), nor did regression analysis reveal any likely predictive relationships to leukocyte values. The results of this study demonstrate the competence of the dog as a host for B. malayi and its potential to serve in the laboratory role currently provided by the cat, while also clarifying the potential for zoonosis in filariasis-endemic regions.

Injury-related deaths in the Ontario provincial trauma system: a retrospective population-based cohort analysis.

BACKGROUND: Although Ontario has an established trauma system, it experiences a substantial burden of morbidity and mortality from injury. Our objective was to describe patterns of fatal injury in Ontario, with a focus on location of death (out of hospital, trauma or non-trauma centre) and receipt of surgical intervention before death. METHODS: We conducted a retrospective population-based cohort study using linked administrative data on fatal injuries in children and adults (no age restrictions) in Ontario between 2000 and 2016. We identified injury-related deaths in the Ontario Registrar General Death database. We developed descriptive statistics for injury characteristics and causes of death. We calculated the fatal injury incidence rate for each year of the study. The primary outcome was cause of death; the secondary outcome was receipt of surgical intervention. RESULTS: The analysis included 19 408 people. The mean annual incidence of fatal injury averaged 8.7 (95% confidence interval 7.7-9.6) per 100 000. The most common mechanisms of injury were motor vehicle collisions (12 065, 62.2%), followed by gunshot wounds (3134, 16.1%) and falls (2387, 12.3%). Deaths frequently occurred out of hospital (72.6%), rather than at a trauma centre (14.2%) or non-trauma centre (13.2%). Patients treated at trauma centres were significantly more likely to receive a surgical intervention (standardized difference 0.6) than those treated at non-trauma centres. INTERPRETATION: Most injury deaths in Ontario occur in the out-of-hospital setting or are managed at non-trauma centres; many patients receive no surgical intervention before death. There are likely opportunities to improve access to specialized injury care in Ontario's trauma system.