Universal logic with encoded spin qubits in silicon.

Quantum computation features known examples of hardware acceleration for certain problems, but is challenging to realize because of its susceptibility to small errors from noise or imperfect control. The principles of fault tolerance may enable computational acceleration with imperfect hardware, but they place strict requirements on the character and correlation of errors1. For many qubit technologies2-21, some challenges to achieving fault tolerance can be traced to correlated errors arising from the need to control qubits by injecting microwave energy matching qubit resonances. Here we demonstrate an alternative approach to quantum computation that uses energy-degenerate encoded qubit states controlled by nearest-neighbour contact interactions that partially swap the spin states of electrons with those of their neighbours. Calibrated sequences of such partial swaps, implemented using only voltage pulses, allow universal quantum control while bypassing microwave-associated correlated error sources1,22-28. We use an array of six 28Si/SiGe quantum dots, built using a platform that is capable of extending in two dimensions following processes used in conventional microelectronics29. We quantify the operational fidelity of universal control of two encoded qubits using interleaved randomized benchmarking30, finding a fidelity of 96.3% ± 0.7% for encoded controlled NOT operations and 99.3% ± 0.5% for encoded SWAP. The quantum coherence offered by enriched silicon5-9,16,18,20,22,27,29,31-37, the all-electrical and low-crosstalk-control of partial swap operations1,22-28 and the configurable insensitivity of our encoding to certain error sources28,33,34,38 all combine to offer a strong pathway towards scalable fault tolerance and computational advantage.

Time-restricted feeding reveals a role for neural respiratory clocks in optimizing daily ventilatory-metabolic coupling in mice.

The master circadian clock, located in the suprachiasmatic nuclei (SCN), organizes the daily rhythm in minute ventilation (V̇e). However, the extent that the daily rhythm in V̇e is secondary to SCN-imposed O2 and CO2 cycles (i.e., metabolic rate) or driven by other clock mechanisms remains unknown. Here, we experimentally shifted metabolic rate using time-restricted feeding (without affecting light-induced synchronization of the SCN) to determine the influence of metabolic rate in orchestrating the daily V̇e rhythm. Mice eating predominantly at night exhibited robust daily rhythms in O2 consumption (V̇o2), CO2 production (V̇co2), and V̇e with similar peak times (approximately ZT18) that were consistent with SCN organization. However, feeding mice exclusively during the day separated the relative timing of metabolic and ventilatory rhythms, resulting in an approximately 8.5-h advance in V̇co2 and a disruption of the V̇e rhythm, suggesting opposing circadian and metabolic influences on V̇e. To determine if the molecular clock of cells involved in the neural control of breathing contributes to the daily V̇e rhythm, we examined V̇e in mice lacking BMAL1 in Phox2b-expressing respiratory cells (i.e., BKOP mice). The ventilatory and metabolic rhythms of predominantly night-fed BKOP mice did not differ from wild-type mice. However, in contrast to wild-type mice, exclusive day feeding of BKOP mice led to an unfettered daily V̇e rhythm with a peak time aligning closely with the daily V̇co2 rhythm. Taken together, these results indicate that both daily V̇co2 changes and intrinsic circadian time-keeping within Phox2b respiratory cells are predominant orchestrators of the daily rhythm in ventilation.NEW & NOTEWORTHY The master circadian clock organizes the daily rhythm in ventilation; however, the extent that this rhythm is driven by SCN regulation of metabolic rate versus other clock mechanisms remains unknown. We report that metabolic rate alone is insufficient to explain the daily oscillation in ventilation and that neural respiratory clocks within Phox2b-expressing cells additionally optimize breathing. Collectively, these findings advance our mechanistic understanding of the circadian rhythm in ventilatory control.

Potentially Modifiable Risk Factors for Dementia and Mild Cognitive Impairment: An Umbrella Review and Meta-Analysis.

INTRODUCTION: The prevalence of mild and major neurocognitive disorders (NCDs), also referred to as mild cognitive impairment and dementia, is rising globally. The prevention of NCDs is a major global public health interest. We sought to synthesize the literature on potentially modifiable risk factors for NCDs. METHODS: We conducted an umbrella review using a systematic search across multiple databases to identify relevant systematic reviews and meta-analyses. Eligible reviews examined potentially modifiable risk factors for mild or major NCDs. We used a random-effects multi-level meta-analytic approach to synthesize risk ratios for each risk factor while accounting for overlap in the reviews. We further examined risk factors for major NCD due to two common etiologies: Alzheimer's disease and vascular dementia. RESULTS: A total of 45 reviews with 212 meta-analyses were synthesized. We identified fourteen broadly defined modifiable risk factors that were significantly associated with these disorders: alcohol consumption, body weight, depression, diabetes mellitus, diet, hypertension, less education, physical inactivity, sensory loss, sleep disturbance, smoking, social isolation, traumatic brain injury, and vitamin D deficiency. All 14 factors were associated with the risk of major NCD, and five were associated with mild NCD. We found considerably less research for vascular dementia and mild NCD. CONCLUSION: Our review quantifies the risk associated with 14 potentially modifiable risk factors for mild and major NCDs, including several factors infrequently included in dementia action plans. Prevention strategies should consider approaches that reduce the incidence and severity of these risk factors through health promotion, identification, and early management.

SARS-CoV-2, Tdap, and influenza vaccination during pregnancy from 2019 to 2022 in Ontario, Canada: a population-based retrospective cohort study.

BACKGROUND: Hesitancy about vaccination during pregnancy posed challenges to SARS-CoV-2 vaccination efforts. We aimed to examine rates of SARS-CoV-2 vaccination among Ontario residents who gave birth in early 2022, and to compare rates of SARS-CoV-2 vaccine uptake with rates of tetanus, diphtheria, and pertussis (Tdap) and influenza vaccination during pregnancy in 2019, 2021, and 2022. METHODS: We conducted a population-based retrospective cohort study to describe vaccination rates among pregnant and comparable nonpregnant populations in Ontario using linked administrative data. Provincially insured females who had a live, in-hospital birth from Jan. 1 to Mar. 31 in 2019, 2021, or 2022 were our primary cohort. Using log-binomial regression, we tested associations between SARS-CoV-2 (2022) and Tdap and influenza (2019, 2021, 2022) vaccination status, with birth group and covariates. We compared SARS-CoV-2 vaccination status with the status of a matched cohort of nonpregnant females and conducted subgroup analyses by age and prenatal clinician type. RESULTS: Among birthing people, 78.7% received their first SARS-CoV-2 vaccine dose and 74.2% received a second dose. The rate was significantly higher among nonpregnant comparators (dose 1: relative risk [RR] 0.94, 95% confidence interval [CI] 0.93-0.94; dose 2: RR 0.91, 95% CI 0.90-0.91). However, the rate of SARS-CoV-2 vaccination uptake among birthing people was higher than uptake of Tdap or influenza vaccination. Tetanus, diphtheria, and pertussis vaccination increased over time from 22.2% in 2019 to 32.6% in 2022, and influenza vaccination rose to 35.3% in 2021 but returned to prepandemic levels in 2022 (27.7%). Vaccination rates were lower among pregnant people who were young, multiparous, or residents of rural or economically deprived areas for all 3 vaccines. INTERPRETATION: Rates of SARS-CoV-2 vaccination were lower among pregnant people than among nonpregnant comparators but were higher than rates of routinely recommended Tdap and influenza vaccinations. Pandemic urgency may have overcome a great deal of hesitancy about vaccinating against SARS-CoV-2 during pregnancy in 2022, but uptake of routinely recommended vaccines in pregnancy remains a challenge. TRIAL REGISTRATION: Clinicaltrials.gov, no. NCT05663762.

Evaluating methods for risk prediction of Covid-19 mortality in nursing home residents before and after vaccine availability: a retrospective cohort study.

BACKGROUND: SARS-CoV-2 vaccines are effective in reducing hospitalization, COVID-19 symptoms, and COVID-19 mortality for nursing home (NH) residents. We sought to compare the accuracy of various machine learning models, examine changes to model performance, and identify resident characteristics that have the strongest associations with 30-day COVID-19 mortality, before and after vaccine availability. METHODS: We conducted a population-based retrospective cohort study analyzing data from all NH facilities across Ontario, Canada. We included all residents diagnosed with SARS-CoV-2 and living in NHs between March 2020 and July 2021. We employed five machine learning algorithms to predict COVID-19 mortality, including logistic regression, LASSO regression, classification and regression trees (CART), random forests, and gradient boosted trees. The discriminative performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC) for each model using 10-fold cross-validation. Model calibration was determined through evaluation of calibration slopes. Variable importance was calculated by repeatedly and randomly permutating the values of each predictor in the dataset and re-evaluating the model's performance. RESULTS: A total of 14,977 NH residents and 20 resident characteristics were included in the model. The cross-validated AUCs were similar across algorithms and ranged from 0.64 to 0.67. Gradient boosted trees and logistic regression had an AUC of 0.67 pre- and post-vaccine availability. CART had the lowest discrimination ability with an AUC of 0.64 pre-vaccine availability, and 0.65 post-vaccine availability. The most influential resident characteristics, irrespective of vaccine availability, included advanced age (≥ 75 years), health instability, functional and cognitive status, sex (male), and polypharmacy. CONCLUSIONS: The predictive accuracy and discrimination exhibited by all five examined machine learning algorithms were similar. Both logistic regression and gradient boosted trees exhibit comparable performance and display slight superiority over other machine learning algorithms. We observed consistent model performance both before and after vaccine availability. The influence of resident characteristics on COVID-19 mortality remained consistent across time periods, suggesting that changes to pre-vaccination screening practices for high-risk individuals are effective in the post-vaccination era.

Length of Postpartum Hospital Stays During COVID-19: Findings From a Convergent Parallel Mixed-Methods Study.

OBJECTIVES: We examined the length of postpartum hospitalization for live births during the COVID-19 pandemic and explored how pandemic circumstances influenced postpartum hospital experiences. METHODS: We conducted a cross-provincial, convergent parallel mixed-methods study in Ontario (ON) and British Columbia (BC), Canada. We included birthing persons (BPs) with an in-hospital birth in ON from 1 January to 31 March 2019, 2021, and 2022 (quantitative), and BPs (≥18 years) in ON or BC from 1 May 2020 to 1 December 2021 (qualitative). We linked multiple health administrative datasets at ICES and developed multivariable linear regression models to examine the length of hospital stay (quantitative). We conducted semi-structured interviews using qualitative descriptive to understand experiences of postpartum hospitalization (qualitative). Data integration occurred during design and interpretation. RESULTS: Relative to 2019, postpartum hospital stays decreased significantly by 3.29 hours (95% CI -3.58 to -2.99; 9.2% reduction) in 2021 and 3.89 hours (95% CI -4.17 to -3.60; 9.0% reduction) in 2022. After adjustment, factors associated with shortened stays included: giving birth during COVID-19, social deprivation (more ethnocultural diversity), midwifery care, multiparity, and lower newborn birth weight. Postpartum hospital experiences were impacted by risk perception of COVID-19 infection, clinical care and hospital services/amenities, visitor policies, and duration of stay. CONCLUSIONS: Length of postpartum hospital stays decreased during COVID-19, and qualitative findings described unmet needs for postpartum services. The integration of large administrative and interview data expanded our understanding of observed differences. Future research should investigate the impacts of shortened stays on health service outcomes and personal experiences.

Association between delayed outbreak identification and SARS-CoV-2 infection and mortality among long-term care home residents, Ontario, Canada, March to November 2020: a cohort study.

BackgroundLate outbreak identification is a common risk factor mentioned in case reports of large respiratory infection outbreaks in long-term care (LTC) homes.AimTo systematically measure the association between late SARS-CoV-2 outbreak identification and secondary SARS-CoV-2 infection and mortality in residents of LTC homes.MethodsWe studied SARS-CoV-2 outbreaks across LTC homes in Ontario, Canada from March to November 2020, before the COVID-19 vaccine rollout. Our exposure (late outbreak identification) was based on cumulative infection pressure (the number of infectious resident-days) on the outbreak identification date (early: ≤ 2 infectious resident-days, late: ≥ 3 infectious resident-days), where the infectious window was -2 to +8 days around onset. Our outcome consisted of 30-day incidence of secondary infection and mortality, based on the proportion of at-risk residents with a laboratory-confirmed SARS-CoV-2 infection with onset within 30 days of the outbreak identification date.ResultsWe identified 632 SARS-CoV-2 outbreaks across 623 LTC homes. Of these, 36.4% (230/632) outbreaks were identified late. Outbreaks identified late had more secondary infections (10.3%; 4,437/42,953) and higher mortality (3.2%; 1,374/42,953) compared with outbreaks identified early (infections: 3.3%; 2,015/61,714; p < 0.001, mortality: 0.9%; 579/61,714; p < 0.001). After adjustment for 12 LTC home covariates, the incidence of secondary infections in outbreaks identified late was 2.90-fold larger than that of outbreaks identified early (OR: 2.90; 95% CI: 2.04-4.13).ConclusionsThe timeliness of outbreak identification could be used to predict the trajectory of an outbreak, plan outbreak measures and retrospectively provide feedback for quality improvement, with the objective of reducing the impacts of respiratory infections in LTC home residents.

Characteristics of family physicians with additional training or focused practices in caring for older adults: Population-based retrospective cohort study.

OBJECTIVE: To identify FPs with additional training and focused practice activities relevant to the needs of older patients within health administrative data and to describe their medical practices and service provision in community-based primary care settings. DESIGN: Retrospective cohort study. SETTING: Ontario. PARTICIPANTS: Family physicians with Certificates of Added Competence in care of the elderly from the College of Family Physicians of Canada or focused practice billing designations in care of the elderly. MAIN OUTCOME MEASURES: Evidence of additional training or certification in care of the elderly or practice activities relevant to the care of older adults. RESULTS: Of 14,123 FPs, 242 had evidence of additional scope to better support older adults. These FPs mainly practised in team-based care models, tended to provide comprehensive care, and billed for core primary care services. In an unadjusted analysis, factors statistically significantly associated with greater likelihood of having additional training or focused practices relevant to the care of older patients included physician demographic characteristics (eg, female sex, having completed medical school in Canada, residential instability at the community level), primary care practice model (ie, focused practice type), primary care activities (eg, more likely to provide consultations, practise in long-term care, refer patients to psychiatry and geriatrics, bill for complex house call assessments, bill for home care applications, and bill for long-term care health report forms), and patient characteristics (ie, older average age of patients). CONCLUSION: The FP workforce with additional training or focused practices in caring for older patients represents a small but specialized group of providers who contribute a portion of the total primary care activities for older adults. Health human resource planning should consider the contributions of all FPs who care for older adults, and enhancing geriatric competence across the family medicine workforce should be emphasized.

The Integrated Care Team: A primary care based-approach to support older adults with complex health needs.

Many older adults have complex needs and experience high rates of acute care use and institutionalization. Comprehensive Geriatric Assessment (CGA) is a specialized multidimensional interprofessional intervention to prevent such outcomes, but access to CGA in the community is limited. The Integrated Care Team (ICT) is a proactive case-finding intervention to support older adults with complex needs in primary care. The ICT provides nurse practitioner-led shared-care supported by a pharmacist, family physician, and geriatrician. Patients undergo a CGA, and a person-centred plan of care is implemented. We conducted a mixed-methods evaluation of the ICT. Patients were 81 ± 9.2 years old, 71% were women. Patients had a high burden of dementia and multimorbidity and received 12.8 ± 5.8 prescriptions daily. The ICT improved prescribing and reduced emergency department visits by 49.5% (P = 0.0001). Patients, care partners, and referring physicians reported high satisfaction with care. The ICT is currently being expanded to support additional primary care providers.

Examining the effect of the COVID-19 pandemic on community virus prevalence and healthcare utilisation reveals that peaks in asthma, COPD and respiratory tract infection occur with the re-emergence of rhino/enterovirus.

INTRODUCTION: Airway disease exacerbations are cyclical related to respiratory virus prevalence. The COVID-19 pandemic has been associated with reduced exacerbations possibly related to public health measures and their impact on non-COVID-19 respiratory viruses. We aimed to investigate the prevalence of non-COVID-19 respiratory viruses during the pandemic compared with prior in Ontario, Canada and healthcare utilisation related to asthma, chronic obstructive pulmonary disease (COPD) and respiratory tract infection. METHODS: This is a population-based retrospective analysis of respiratory virus tests, emergency department (ED) visits and hospitalisations between 2015 and 2021 in Ontario. Weekly virus testing data were used to estimate viral prevalence for all non-COVID-19 respiratory viruses. We plotted the %positivity and observed and expected counts of each virus to visualise the impact of the pandemic. We used Poisson and binomial logistic regression models to estimate the change in %positivity, count of positive viral cases and count of healthcare utilisation during the pandemic. RESULTS: The prevalence of all non-COVID-19 respiratory viruses decreased dramatically during the pandemic compared with prior. Comparing periods, the incidence rate ratio (IRR) for positive cases corresponded to a >90% reduction for non-COVID-19 respiratory viruses except adenovirus and rhino/enterovirus. Asthma-related ED visits and hospital admissions fell by 57% (IRR 0.43 (95% CI 0.37 to 0.48)) and 61% (IRR 0.39 (95% CI 0.33 to 0.46)). COPD-related ED visits and admissions fell by 63% (IRR 0.37 (95% CI 0.30 to 0.45)) and 45% (IRR 0.55 (95% CI 0.48 to 0.62)). Respiratory tract infection ED visits and admissions fell by 85% (IRR 0.15 (95% CI 0.10 to 0.22)), and 85% (IRR 0.15 (95% CI 0.09 to 0.24)). Rather than the usual peaks in disease condition, during the pandemic, healthcare utilisation peaked in October when rhino/enterovirus peaked. CONCLUSIONS: The prevalence of nearly all non-COVID-19 respiratory viruses decreased during the pandemic and was associated with marked reductions in ED visits and hospitalisations. The re-emergence of rhino/enterovirus was associated with increased healthcare utilisation.

Single and coupled cavity mode sensing schemes using a diagnostic field.

Precise optical mode matching is of critical importance in experiments using squeezed-vacuum states. Automatic spatial-mode matching schemes have the potential to reduce losses and improve loss stability. However, in quantum-enhanced coupled-cavity experiments, such as gravitational-wave detectors, one must also ensure that the sub-cavities are also mode matched. We propose what we believe to be a new mode sensing scheme, which works for simple and coupled cavities. The scheme requires no moving parts, nor tuning of Gouy phases. Instead a diagnostic field tuned to the HG20/LG10 mode frequency is used. The error signals are derived to be proportional to the difference in waist position, and difference in Rayleigh ranges, between the sub-cavity eigenmodes. The two error signals are separable by 90 degrees of demodulation phase. We demonstrate reasonable error signals for a simplified Einstein Telescope optical design. This work will facilitate routine use of extremely high levels of squeezing in current and future gravitational-wave detectors.

The Impact of Poorly Differentiated Histology on Immunotherapy in Advanced Gastrointestinal Cancers.

INTRODUCTION: Checkpoint inhibitors (CPI) have significantly improved survival among patients with various cancer types. Prior studies have shown a correlation between immune cell infiltration and poorly differentiated cancers. This study evaluated the impact of poorly differentiated histology on survival in patients with advanced gastrointestinal cancers treated with immunotherapy. METHODS: This study was a retrospective, single-center analysis of patients with gastrointestinal cancers treated with CPIs between 2016 and 2021. Univariate and multivariable analyses were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between tumor and patient characteristics, progression-free survival, and overall survival. RESULTS: A total of 123 patients were eligible and included in the analysis. Median age was 66 years (23-88 years). Majority had stage IV disease (89%), were white (65.5%), and were male (64.5%). Most common diagnoses were hepatocellular carcinoma (30.5%), gastric adenocarcinoma (16.5%), esophageal adenocarcinoma (17%), and colorectal cancer (19.8%). About 32% of the tumors were microsatellite instability-high (MSI-High/dMMR), with BRAF V600E mutation rate of 10%. About 25% of the patients received CPIs as initial treatment, while 35.5% had received two or more prior lines of therapy. Compared with well and moderately differentiated histology, patients with poorly differentiated tumors had a shorter median overall survival (mOS) (not reached [NR] vs. NR vs. 9.3 months, p = 0.0264). There was no statistically significant difference in median progression-free survival (mPFS) between histology types (2.5 vs. 4.2 vs. 2 months, p = 0.1314). On univariate survival analysis, moderately differentiated tumors correlated with a significantly longer mOS (HR: 0.48, CI: 0.24-0.93, p = 0.030) and mPFS (HR: 0.62, 95% CI: 0.38-1.00, p = 0.048) compared to poorly differentiated histology. Female patients (HR: 0.55, 95% CI: 0.34-0.90, p = 0.018) and the Eastern Cooperative Oncology Group (ECOG) of 1 (vs. ≥2) had significantly longer mPFS (HR: 0.58, 95% CI: 0.35-0.97, p = 0.036). ECOG of 1 also correlated with longer mOS (HR: 0.47, 95% CI: 0.23-0.94, p = 0.034). Microsatellite stable (MSS) tumors had significantly shorter mPFS (HR: 5.74, 95% CI: 2.41-13.63, p < 0.001) and mOS (HR: 5.45, 95% CI: 1.64-18.12, p = 0.006). The number of prior systemic therapies was also associated with shorter mPFS (HR: 1.19, 95% CI: 1.03-1.39, p = 0.022) and mOS (HR: 1.23, 95% CI: 1.01-1.50, p = 0.045). On multivariable analyses, ECOG status of 0/1 versus ≥2 and MSI-High/dMMR versus MSS remained significantly associated with longer mPFS and mOS. There was no correlation with histologic differentiation status, race, or mutations such as BRAF V600E or KRAS. CONCLUSION: Results from this study demonstrate that poorly differentiated histology was associated with shorter mOS but was not associated with improved PFS in patients treated with CPI. Treatment-naïve patients, moderately differentiated tumors, female gender, ECOG 1, and MSI-High/dMMR were most likely to benefit from CPI.

The association between frailty, long-term care home characteristics and COVID-19 mortality before and after SARS-CoV-2 vaccination: a retrospective cohort study.

BACKGROUND: The relative contributions of long-term care (LTC) resident frailty and home-level characteristics on COVID-19 mortality has not been well studied. We examined the association between resident frailty and home-level characteristics with 30-day COVID-19 mortality before and after the availability of SARS-CoV-2 vaccination in LTC. METHODS: We conducted a population-based retrospective cohort study of LTC residents with confirmed SARS-CoV-2 infection in Ontario, Canada. We used multi-level multivariable logistic regression to examine associations between 30-day COVID-19 mortality, the Hubbard Frailty Index (FI), and resident and home-level characteristics. We compared explanatory models before and after vaccine availability. RESULTS: There were 11,179 and 3,655 COVID-19 cases in the pre- and post-vaccine period, respectively. The 30-day COVID-19 mortality was 25.9 and 20.0% during the same periods. The median odds ratios for 30-day COVID-19 mortality between LTC homes were 1.50 (95% credible interval [CrI]: 1.41-1.65) and 1.62 (95% CrI: 1.46-1.96), respectively. In the pre-vaccine period, 30-day COVID-19 mortality was higher for males and those of greater age. For every 0.1 increase in the Hubbard FI, the odds of death were 1.49 (95% CI: 1.42-1.56) times higher. The association between frailty and mortality remained consistent in the post-vaccine period, but sex and age were partly attenuated. Despite the substantial home-level variation, no home-level characteristic examined was significantly associated with 30-day COVID-19 mortality during either period. INTERPRETATION: Frailty is consistently associated with COVID-19 mortality before and after the availability of SARS-CoV-2 vaccination. Home-level characteristics previously attributed to COVID-19 outcomes do not explain significant home-to-home variation in COVID-19 mortality.

Frailty prevalence and efficient screening in primary care-based memory clinics.

BACKGROUND: Little is known about the prevalence of frailty among patients with memory concerns attending a primary care-based memory clinic. OBJECTIVE: This study aims to describe the prevalence of frailty among patients attending a primary care-based memory clinic and to determine if prevalence rates differ based on the screening tool that is used. METHODS: We conducted a retrospective medical record review for all consecutive patients assessed in a primary care-based memory clinic over 8 months. Frailty was measured in 258 patients using the Fried frailty criteria, which relies on physical measures, and the Clinical Frailty Scale (CFS), which relies on functional status. Weighted kappa statistics were calculated to compare the Fried frailty and the CFS. RESULTS: The prevalence of frailty was 16% by Fried criteria and 48% by the CFS. Agreement between Fried frailty and CFS was fair for CFS 5+ (kappa = 0.22; 95% confidence interval: 0.13, 0.32) and moderate for CFS 6+ (kappa = 0.47; 0.34, 0.61). Dual-trait measures of hand grip strength with gait speed were found to be a valid proxy for Fried frailty phenotype. CONCLUSIONS: Among primary care patients with memory concerns, frailty prevalence rates differed based on the measure used. Screening for frailty in this population using measures relying on physical performance may be a more efficient approach for persons already at risk of further health instability from cognitive impairment. Our findings demonstrate how measure selection should be based on the objectives and context in which frailty screening occurs.

There is some evidence that frailty and dementia are inter-related. This study aimed to describe the prevalence of frailty among patients attending a primary care-based memory clinic using 2 commonly used frailty measures: the Fried frailty phenotype criteria and the Clinical Frailty Scale (CFS). Frailty prevalence in patients with memory concerns is at least double that of regular primary care practice; prevalence is 16% when the Fried frailty phenotype is used, which incorporates physical frailty measures, as compared with prevalence of 48% when the more function-based measure of CFS is used. Screening tools should be selected considering the objectives and context in which they are used. Within primary care-based memory clinics, physical frailty measures may be most optimal. Using hand grip and gait speed screening as a valid proxy for Fried frailty phenotype offers a feasible and practical way of identifying frailty relating more to physical underlying conditions. Based on our study findings, frailty screening within primary care-based memory clinics is justified for patients 65 years+; early identification and intervention may prevent further decline and adverse outcomes. Further research in this area will increase our understanding of frailty and dementia in this context and how to best plan care.

Recent functional decline and outpatient follow-up after hospital discharge: a cohort study.

BACKGROUND: Functional decline is common following acute hospitalization and is associated with hospital readmission, institutionalization, and mortality. People with functional decline may have difficulty accessing post-discharge medical care, even though early physician follow-up has the potential to prevent poor outcomes and is integral to high-quality transitional care. We sought to determine whether recent functional decline was associated with lower rates of post-discharge physician follow-up, and whether this association changed during the COVID-19 pandemic, given that both functional decline and COVID-19 may affect access to post-discharge care. METHOD: We conducted a retrospective cohort study using health administrative data from Ontario, Canada. We included patients over 65 who were discharged from an acute care facility during March 1st, 2019 - January 31st, 2020 (pre-COVID-19 period), and March 1st, 2020 - January 31st, 2021 (COVID-19 period), and who were assessed for home care while in hospital. Patients with and without functional decline were compared. Our primary outcome was any physician follow-up visit within 7 days of discharge. We used propensity score weighting to compare outcomes between those with and without functional decline. RESULTS: Our study included 21,771 (pre-COVID) and 17,248 (COVID) hospitalized patients, of whom 15,637 (71.8%) and 12,965 (75.2%) had recent functional decline. Pre-COVID, there was no difference in physician follow-up within 7 days of discharge (Functional decline 45.0% vs. No functional decline 44.0%; RR = 1.02, 95% CI 0.98-1.06). These results did not change in the COVID-19 period (Functional decline 51.1% vs. No functional decline 49.4%; RR = 1.03, 95% CI 0.99-1.08, Z-test for interaction p = 0.72). In the COVID-19 cohort, functional decline was associated with having a 7-day physician virtual visit (RR 1.15; 95% CI 1.08-1.24) and a 7-day physician home visit (RR 1.64; 95% CI 1.10-2.43). CONCLUSIONS: Functional decline was not associated with reduced 7-day post-discharge physician follow-up in either the pre-COVID-19 or COVID-19 periods. In the COVID-19 period, functional decline was positively associated with 7-day virtual and home-visit follow-up.

Medical treatments for idiopathic pulmonary fibrosis: a systematic review and network meta-analysis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a respiratory disorder with a poor prognosis. Our objective is to assess the comparative effectiveness of 22 approved or studied IPF drug treatments. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and clinicaltrials.gov from inception to 2 April 2021. We included randomised controlled trials (RCTs) for adult patients with IPF receiving one or more of 22 drug treatments. Pairs of reviewers independently identified randomised trials that compared one or more of the target medical treatments in patients with IPF. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for network meta-analysis. We calculated pooled relative risk (RR) ratios and presented direct or network estimates with 95% credibility intervals (95% CI), within the GRADE framework. RESULTS: We identified 48 (10 326 patients) eligible studies for analysis. Nintedanib [RR 0.69 (0.44 to 1.1), pirfenidone [RR 0.63 (0.37 to 1.09); direct estimate), and sildenafil [RR (0.44 (0.16 to 1.09)] probably reduce mortality (all moderate certainty). Nintedanib (2.92% (1.51 to 4.14)), nintedanib+sildenafil (157 mL (-88.35 to 411.12)), pirfenidone (2.47% (-0.1 to 5)), pamrevlumab (4.3% (0.5 to 8.1)) and pentraxin (2.74% (1 to 4.83)) probably reduce decline of overall forced vital capacity (all moderate certainty). Only sildenafil probably reduces acute exacerbation and hospitalisations (moderate certainty). Corticosteroids+azathioprine+N-acetylcysteine increased risk of serious adverse events versus placebo (high certainty). CONCLUSION AND RELEVANCE: Future guidelines should consider sildenafil for IPF and further research needs to be done on promising IPF treatments such as pamrevlumab and pentraxin as phase 3 trials are completed.

Observing the optical modes of parametric instability.

Parametric instability (PI) is a phenomenon that results from resonant interactions between optical and acoustic modes of a laser cavity. This is problematic in gravitational wave interferometers where the high intracavity power and low mechanical loss mirror suspension systems create an environment where three-mode PI will occur without intervention. We demonstrate a technique for real-time imaging of the amplitude and phase of the optical modes of PI yielding, to the best of the authors' knowledge, the first ever images of this phenomenon which could form part of active control strategies for future detectors.

Comparing Somatostatin Analogs in the Treatment of Advanced Gastroenteropancreatic Neuroendocrine Tumors.

BACKGROUND: The 2 approved somatostatin analogs (SSAs) in the first-line treatment of advanced, well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are octreotide long-acting release (Sandostatin LAR) and somatuline depot (Lanreotide). The study's objective was to compare progression-free survival (PFS) and overall survival (OS) of patients (pts) with GEP-NETs treated with somatuline or octreotide LAR. Pts and Methods: Pts with advanced well-differentiated GEP-NET who received either SSA at Emory University between 1995 and 2019 were included after institutional review board approval. The primary end point was PFS, defined as time to disease progression (according to the Response Evaluation Criteria in Solid Tumors, version 1.1, or clinical progression) or death. The secondary end point was OS. Kaplan-Meier curves were generated, and log-rank tests were conducted to compare the survival outcomes. RESULTS: A total of 105 pts were identified. The mean age was 62.1 years (SD ± 11.8). The male-to-female ratio was 51:54. The majority (N = 69, 65.7%) were white. Most pts had grade 2 (G2) disease (N = 44, 41.9%). Primary location was small bowel in 58 (55.2%), pancreas in 27 (25.7%), and other in 20 (19.0%). Functional tumors were defined in 32 pts distributed equally between the 2 groups. Distribution of treatment was similar in the 2 groups, with 54 receiving octreotide LAR and 51 receiving somatuline depot. The median PFS for the octreotide LAR and somatuline depot groups was 12 months (95% CI, 6-18 months) and 10.8 months (95% CI, 6-15.6 months), respectively, and the difference was not statistically significant (p = 0.2665). For pts with G1 disease, the median PFS for the octreotide LAR and somatuline depot was 8.4 versus 32.4 months, respectively, and the difference was not statistically significant (p = 0.159). For G2 disease, the difference in median PFS between octreotide LAR and somutaline depot groups was statistically significant (12 vs. 7.2 months, respectively; p = 0.0372). The mean follow-up time for octreotide LAR was 21.6 months versus 11.3 months for somatuline depot. CONCLUSIONS: Overall, there was no difference in PFS between octreotide LAR and somatuline depot for pts with well-differentiated, metastatic GEP-NETs. A prospective study is worth designing selecting for G.

Sildenafil for idiopathic pulmonary fibrosis: A systematic review and meta-analysis.

BACKGROUND: Patients with idiopathic pulmonary fibrosis have a poor overall prognosis and there are few evidence-based drug therapies that reduce mortality. OBJECTIVE: We aimed to perform a systematic review and meta-analysis to assess whether sildenafil reduces mortality, disease progression and adverse side effects. METHODS: We reviewed randomized controlled studies (RCTs) from MEDLINE, Cochrane registry of clinical trials, and EMBASE. Our outcomes of interest included mortality, change in FVC, acute exacerbations and hospitalizations and adverse drug effects leading to discontinuation. We used an inverse variance fixed effects meta-analysis method to calculate pooled relative risk (RR) and mean difference (MD). RESULTS: A total of 4 studies were included in the systematic review. Sildenafil probably reduces mortality when compared to placebo or to standard care, [RR 0.73 (95% CI 0.51 to 1.04); moderate certainty]. Pooled estimates showed sildenafil may not alter the rate of change of FVC [MD 0.61% (95% CI -0.29 to 1.52)], or DLCO [MD 0.97% (95% CI 0.04 to 1.90)] (both low certainty). Pooled estimated showed sildenafil may not reduce the number of hospitalizations or acute exacerbations, [RR 1.10 (95% CI 0.61 to 1.98); low certainty]. There is probably no difference in drug discontinuation due to adverse effects when comparing sildenafil to the control group, [RR 0.79 (95% CI 0.56, 1.10); moderate certainty]. CONCLUSION: Sildenafil probably reduces all-cause mortality in IPF patients. More studies need to be done to confirm the magnitude and reliability of the point estimate.

"No-regrets" pathways for navigating climate change: planning for connectivity with land use, topography, and climate.

As both plant and animal species shift their ranges in response to a changing climate, maintaining connectivity between present habitat and suitable habitat in the future will become increasingly important to ensure lasting protection for biodiversity. Because the temporal period commensurate with planning for mid-century change is multi-generational for most species, connectivity designed to facilitate climate adaptation requires pathways with 'stepping-stones' between current and future habitat. These areas should have habitats suitable not only for dispersal, but for all aspects of species lifecycles. We integrated present-day land use, topographic diversity, and projections of shifting climate regimes into a single connectivity modeling approach to identify pathways for mid-century shifts in species ranges. Using Omniscape we identified climate linkages, or areas important for climate change-driven movement, as the areas with more current flow than would be expected in the absence of climate considerations. This approach identified connectivity potential between natural lands in the present climate and natural lands with future analogous climate following topo-climatically diverse routes. We then translated the model output into a strategic framework to improve interpretation and to facilitate a more direct connection with conservation action. Across modified landscapes, pathways important to climate-driven movement were highly coincident with the last remaining present-day linkages, reinforcing their importance. Across unfragmented lands, the presence of climate-adapted pathways helped inform the prioritization of conservation actions in areas where multiple connectivity options still exist. Many climate linkages follow major watercourses along elevational gradients, highlighting the importance of protecting or managing for these natural linear pathways that provide movement routes for climate adaptation. By integrating enduring landscape features with climate projections and present-day land uses, our approach reveals "no-regrets" pathways to plan for a connected landscape in an uncertain future.