bluuebunny/crossref_metadata_2025 huggingface dataset:
Micro RNA in meniscal ailments: current concepts
Authors: Migliorini Filippo , Vecchio Gianluca , Giorgino Riccardo , Eschweiler Jörg , Hildebrand Frank , Maffulli Nicola
Published: February 2023

Introduction

Micro RNAs (miRNAs) are short non-coding RNAs that act primarily in posttranscriptional gene silencing, and are attracting increasing interest in musculoskeletal conditions.

Source of data

Current scientific literature published in PubMed, Google Scholar, Embase and Web of Science databases.

Areas of agreement

Recently, the potential of miRNAs as biomarkers for diagnosis and treatment of meniscal injuries has been postulated.

Areas of controversy

Evaluation of the role of miRNAs in patients with meniscal tears is still controversial.

Growing points

A systematic review was conducted to investigate the potential of miRNA in the diagnosis and management of meniscal damage.

Areas timely for developing research

Intra-articular injection of microRNA-210 in vivo may represent a potential innovative methodology for the management of meniscal injuries. Characterization of the miRNAs expression in the synovial fluid could lead to the development of better early diagnosis and management strategies for meniscal tears.
Deciphering the clinico-radiological heterogeneity of dysexecutive Alzheimer’s disease
Authors: Corriveau-Lecavalier Nick , Barnard Leland R , Lee Jeyeon , Dicks Ellen , Botha Hugo , Graff-Radford Jonathan , Machulda Mary M , Boeve Bradley F , Knopman David S , Lowe Val J , Petersen Ronald C , Jack, Jr Clifford R , Jones David T
Published: February 2023

Dysexecutive Alzheimer’s disease (dAD) manifests as a progressive dysexecutive syndrome without prominent behavioral features, and previous studies suggest clinico-radiological heterogeneity within this syndrome. We uncovered this heterogeneity using unsupervised machine learning in 52 dAD patients with multimodal imaging and cognitive data. A spectral decomposition of covariance between FDG-PET images yielded six latent factors (“eigenbrains”) accounting for 48% of variance in patterns of hypometabolism. These eigenbrains differentially related to age at onset, clinical severity, and cognitive performance. A hierarchical clustering on the eigenvalues of these eigenbrains yielded four dAD subtypes, i.e. “left-dominant,” “right-dominant,” “bi-parietal-dominant,” and “heteromodal-diffuse.” Patterns of FDG-PET hypometabolism overlapped with those of tau-PET distribution and MRI neurodegeneration for each subtype, whereas patterns of amyloid deposition were similar across subtypes. Subtypes differed in age at onset and clinical severity where the heteromodal-diffuse exhibited a worse clinical picture, and the bi-parietal had a milder clinical presentation. We propose a conceptual framework of executive components based on the clinico-radiological associations observed in dAD. We demonstrate that patients with dAD, despite sharing core clinical features, are diagnosed with variability in their clinical and neuroimaging profiles. Our findings support the use of data-driven approaches to delineate brain–behavior relationships relevant to clinical practice and disease physiology.
Cardiac sarcoidosis presenting with cardiogenic shock successfully recovered by Impella and corticosteroid pulse therapy: a case report
Authors: Hashimura Miho , Ikeda Yuki , Koitabashi Toshimi , Ako Junya
Published: February 2023

Background

Cardiac sarcoidosis (CS) occasionally disrupts circulatory haemodynamics due to arrhythmia or cardiac dysfunction.

Case summary

A 70-year-old woman was diagnosed with CS, then was admitted for syncope because of complete atrioventricular block and frequently non-sustained ventricular tachycardia. Although a temporary pacemaker and intravenous amiodarone were introduced, she subsequently went into cardiopulmonary arrest by ventricular fibrillation. After the return of spontaneous circulation, Impella cardiac power (CP) was introduced because of sustained hypotension and severely impaired left ventricular contraction. High-dose intravenous corticosteroid therapy was simultaneously introduced. Her atrioventricular conduction and left ventricular contraction drastically improved. Impella CP was successfully removed after 4 days of support. She was eventually administered steroid maintenance therapy and discharged.

Discussion

We report a case of CS with fulminant haemodynamic collapse treated with high-dose intravenous corticosteroid therapy under Impella assistance for acute haemodynamic support. Although CS has been known as an inflammatory disease with progressive cardiac dysfunction and rapid deterioration due to fatal arrhythmias, it can be improved with steroid therapy. It was suggested that strong haemodynamic support by Impella could be a bridge to manifest the effects after introducing steroid therapy to patients with CS.
Suspending Suspensions: The Education Production Consequences of School Suspension Policies*
Authors: Pope Nolan G , Zuo George W
Published: February 2023

Managing student behaviour is integral to the education production process. We study the trade-offs of school suspension policies by modelling and estimating how changes in school suspension policies causally impact student performance and teacher turnover. Our results indicate that the reduction in suspension rates in the Los Angeles Unified School District decreased math and English test scores, decreased grade point averages and increased absences. Teacher turnover also increased, particularly for inexperienced teachers. We also document an efficiency-equity trade-off: while achievement decreased for most students in the district, the highest-risk students experienced moderate gains in achievement.
Political Risk, Populism and the Economy
Authors: Balduzzi Pierluigi , Brancati Emanuele , Brianti Marco , Schiantarelli Fabio
Published: February 2023

We study the financial and real effects of political risk shocks for Italy, Spain, Ireland, Portugal and Greece between 2008 and 2019. We build an instrument for these shocks using the changes of the sovereign yield spread around political and policy dates, and estimate their effects in the context of local projection. We show that adverse political risk shocks have negative effects on domestic financial markets and in some countries generate spillovers on the spreads of other eurozone economies. Moreover, in Italy populism-related political risk shocks have a larger effect on financial markets and they harm the real economy.
Vocational education, tertiary education, and skill use across career stages
Authors: Schulz Wiebke , Solga Heike , Pollak Reinhard
Published: February 2023

Vocational education enhances smooth transitions into the labour market. However, this initial advantage might vanish over the career and eventually turn into a disadvantage because the skills of vocationally trained workers become outdated faster. So far, research has examined this potential vocational trade-off by assessing labour market outcomes such as employment and income. This study uses a different approach, it directly examines how different types of skills used at work change over the career of vocationally trained workers compared to tertiary-educated workers, and how career events shape skill-use changes. With data from the German National Education Study (NEPS), we examine five skills use dimensions based on job-tasks measures: analytical, creative, managerial, interactive, and manual skills. We find that skill-use differentials between vocational and tertiary-educated workers are only small to modest. The clearest differences relate to analytical and manual skills. Looking across career stages, the observed skill-use differentials remain rather stable across career stages—thus, the vocational skill trade-off thesis is only partially supported. Occupational mobility and unemployment contribute to observable changes, whereas job-related further training does not. Our results challenge skill-based explanations of a vocational trade-off.
Endovascular revascularization strategies for aortoiliac and femoropopliteal artery disease: a meta-analysis
Authors: Koeckerling David , Raguindin Peter Francis , Kastrati Lum , Bernhard Sarah , Barker Joseph , Quiroga Centeno Andrea Carolina , Raeisi-Dehkordi Hamidreza , Khatami Farnaz , Niehot Christa , Lejay Anne , Szeberin Zoltan , Behrendt Christian-Alexander , Nordanstig Joakim , Muka Taulant , Baumgartner Iris
Published: February 2023

Aims

Optimal endovascular management of intermittent claudication (IC) remains disputed. This systematic review and meta-analysis compares efficacy and safety outcomes for balloon angioplasty (BA), bare-metal stents (BMS), drug-coated balloons (DCB), drug-eluting stents (DES), covered stents, and atherectomy.

Methods and results

Electronic databases were searched for randomized, controlled trials (RCT) from inception through November 2021. Efficacy outcomes were primary patency, target-lesion revascularization (TLR), and quality-of-life (QoL). Safety endpoints were all-cause mortality and major amputation. Outcomes were evaluated at short-term (<1 year), mid-term (1–2 years), and long-term (≥2 years) follow-up. The study was registered on PROSPERO (CRD42021292639). Fifty-one RCTs enrolling 8430 patients/lesions were included. In femoropopliteal disease of low-to-intermediate complexity, DCBs were associated with higher likelihood of primary patency [short-term: odds ratio (OR) 3.21, 95% confidence interval (CI) 2.44–4.24; long-term: OR 2.47, 95% CI 1.93–3.16], lower TLR (short-term: OR 0.33, 95% CI 0.22–0.49; long-term: OR 0.42, 95% CI 0.29–0.60) and similar all-cause mortality risk, compared with BA. Primary stenting using BMS was associated with improved short-to-mid-term patency and TLR, but similar long-term efficacy compared with provisional stenting. Mid-term patency (OR 1.64, 95% CI 0.89–3.03) and TLR (OR 0.50, 95% CI 0.22–1.11) estimates were comparable for DES vs. BMS. Atherectomy, used independently or adjunctively, was not associated with efficacy benefits compared with drug-coated and uncoated angioplasty, or stenting approaches. Paucity and heterogeneity of data precluded pooled analysis for aortoiliac disease and QoL endpoints.

Conclusion

Certain devices may provide benefits in femoropopliteal disease, but comparative data in aortoiliac arteries is lacking. Gaps in evidence quantity and quality impede identification of the optimal endovascular approach to IC.
Structurally constrained inversion by means of a Minimum Gradient Support regularizer: examples of FD-EMI data inversion constrained by GPR reflection data
Authors: Klose Tim , Guillemoteau Julien , Vignoli Giulio , Walter Judith , Herrmann Andreas , Tronicke Jens
Published: February 2023

Many geophysical inverse problems are known to be ill-posed and, thus, requiring some kind of regularization in order to provide a unique and stable solution. A possible approach to overcome the inversion ill-posedness consists in constraining the position of the model interfaces. For a grid-based parameterization, such a structurally constrained inversion can be implemented by adopting the usual smooth regularization scheme in which the local weight of the regularization is reduced where an interface is expected. By doing so, sharp contrasts are promoted at interface locations while standard smoothness constraints keep affecting the other regions of the model. In this work, we present a structurally constrained approach and test it on the inversion of frequency-domain electromagnetic induction (FD-EMI) data using a regularization approach based on the Minimum Gradient Support stabilizer, which is capable to promote sharp transitions everywhere in the model, i.e., also in areas where no structural a prioriinformation is available. Using 1D and 2D synthetic data examples, we compare the proposed approach to a structurally constrained smooth inversion as well as to more standard (i.e., not structurally constrained) smooth and sharp inversions. Our results demonstrate that the proposed approach helps in finding a better and more reliable reconstruction of the subsurface electrical conductivity distribution, including its structural characteristics. Furthermore, we demonstrate that it allows to promote sharp parameter variations in areas where no structural information are available. Lastly, we apply our structurally constrained scheme to FD-EMI field data collected at a field site in Eastern Germany to image the thickness of peat deposits along two selected profiles. In this field example, we use collocated constant offset ground-penetrating radar (GPR) data to derive structural a priori information to constrain the inversion of the FD-EMI data. The results of this case study demonstrate the effectiveness and flexibility of the proposed approach.
Computing spectral properties of topological insulators without artificial truncation or supercell approximation
Authors: Colbrook Matthew J , Horning Andrew , Thicke Kyle , Watson Alexander B
Published: February 2023

Topological insulators (TIs) are renowned for their remarkable electronic properties: quantized bulk Hall and edge conductivities, and robust edge wave-packet propagation, even in the presence of material defects and disorder. Computations of these physical properties generally rely on artificial periodicity (the supercell approximation, which struggles in the presence of edges), or unphysical boundary conditions (artificial truncation). In this work, we build on recently developed methods for computing spectral properties of infinite-dimensional operators. We apply these techniques to develop efficient and accurate computational tools for computing the physical properties of TIs. These tools completely avoid such artificial restrictions and allow one to probe the spectral properties of the infinite-dimensional operator directly, even in the presence of material defects, edges and disorder. Our methods permit computation of spectra, approximate eigenstates, spectral measures, spectral projections, transport properties and conductances. Numerical examples are given for the Haldane model, and the techniques can be extended similarly to other TIs in two and three dimensions.
Symptom Duration and Resolution With Early Outpatient Treatment of Convalescent Plasma for Coronavirus Disease 2019: A Randomized Trial
Authors: Baksh Sheriza N , Heath Sonya L , Fukuta Yuriko , Shade David , Meisenberg Barry , Bloch Evan M , Tobian Aaron A R , Spivak Emily S , Patel Bela , Gerber Jonathan , Raval Jay S , Forthal Donald , Paxton James , Mosnaim Giselle , Anjan Shweta , Blair Janis , Cachay Edward , Currier Judith , Das Piyali , Huaman Moises , Sutcliffe Catherine , Yarava Anusha , Casadevall Arturo , Sullivan David , Hanley Daniel , Gebo Kelly A
Published: February 2023

Background

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) reduces hospitalizations among outpatients treated early after symptom onset. It is unknown whether CCP reduces time to symptom resolution among outpatients.

Methods

We evaluated symptom resolution at day 14 by trial arm using an adjusted subdistribution hazard model, with hospitalization as a competing risk. We also assessed the prevalence of symptom clusters at day 14 between treatments. Clusters were defined based on biologic clustering, impact on ability to work, and an algorithm.

Results

Among 1070 outpatients followed up after transfusion, 381 of 538 (70.8%) receiving CCP and 381 of 532 (71.6%) receiving control plasma were still symptomatic (P = .78) at day 14. Associations between CCP and symptom resolution by day 14 did not differ significantly from those in controls after adjustment for baseline characteristics (adjusted subdistribution hazard ratio, 0.99; P = .62). The most common cluster consisted of cough, fatigue, shortness of breath, and headache and was found in 308 (57.2%) and 325 (61.1%) of CCP and control plasma recipients, respectively (P = .16).

Conclusions

In this trial of outpatients with early COVID-19, CCP was not associated with faster resolution of symptoms compared with control. Overall, there were no differences by treatment in the prevalence of each symptom or symptom clusters at day 14.

Clinical Trials Registration

NCT04373460.
Second-Phase Hepatitis C Plasma Viral Kinetics Directly Reflects Reduced Intrahepatic Burden of Hepatitis C Virus
Authors: Sachithanandham Jaiprasath , Balagopal Ashwin , Leep-Lazar Julia , Quinn Jeffrey , Bowden Kenneth , Ward Kathleen , Ribeiro Ruy M , Sulkowski Mark S
Published: February 2023

Background

Mathematical models explain how antivirals control viral infections. Hepatitis C virus (HCV) treatment results in at least 2 phases of decline in viremia. The first phase reflects clearance of rapidly produced virions. The second phase is hypothesized to derive from loss of infected cells but has been challenging to prove.

Methods

Using single-cell methods, we quantified the number of hepatitis C virus (HCV)-infected hepatocytes in liver biopsies taken before and within 7 days of initiating direct-acting antivirals (DAAs) in a double-blinded randomized controlled trial testing 2 (sofosbuvir-velpatasvir) versus 3 (sofosbuvir-velpatasvir-voxilaprevir) DAAs.

Results

We employed thousands of intrahepatic measurements in 10 persons with chronic genotype 1a HCV infection: median proportion of infected hepatocytes declined from 11.3% (range, 1.3%–59%) to 0.6% (range, <0.3%–5.8%), a loss of 75%–95% infected hepatocytes. Plasma viremia correlated with numbers of HCV-infected hepatocytes (r = 0.77; P < .0001). Second-phase plasma dynamics and changes in infected hepatocytes were indistinct (P = .16), demonstrating that second-phase viral dynamics derive from loss of infected cells. DAAs led to a decline in intracellular HCV RNA and interferon-stimulated gene expression (P < .05 for both).

Conclusions

We proved that second-phase viral dynamics reflect decay of intrahepatic burden of HCV, partly due to clearance of HCV RNA from hepatocytes.

Clinical Trials Registration

NCT02938013.
Hyperosmotic stress response regulates interstitial homeostasis and pathogenic inflammation
Authors: Sumida Tomokazu S
Published: February 2023

Hyperosmotic stress triggers an evolutionally preserved, fundamental cellular response. A growing body of evidence has highlighted the role of extra-renal, interstitial hyperosmolality in maintaining local tissue immune homeostasis and potentially driving tissue inflammation in human diseases. The hyperosmotic stress response initiates cellular shrinkage, oxidative stress, metabolic remodeling and cell cycle arrest, all of which are adjusted by a counteractive adaptative response that includes osmolyte synthesis, upregulation of ion transporters and induction of heat shock proteins. Recent studies have revealed that high osmolality can impact immune cell differentiation and activation pathways in a cell type specific manner. The fine-tuning of the immune response depends on the tissue microenvironment. Accordingly, novel therapeutic approaches that target hyperosmolality-mediated inflammation may be identified by furthering our understanding of hyperosmotic response in the context of disease. In this review, we discuss the cellular and molecular mechanisms by which hyperosmotic stress response regulates interstitial homeostasis and pathogenic inflammation.
Immunity in the brain and surrounding tissues
Authors: Kanamori Mitsuhiro , Ito Minako
Published: February 2023

Immune reactions in the brain, the most complex organ that directly or indirectly regulates almost every part of the body and its actions, need to be tightly regulated. Recent findings in the field of neuroimmunology have enhanced our understanding of immune cells not only inside the brain but also in adjacent tissues. Multiple types of immune cells exist and are active in neighboring border tissues, even in the steady state. In addition, advances in technology have allowed researchers to characterize a broad range of cell types, including stromal cells that support immune reactions. This review presents a short overview of the roles of the immune system in the brain during health and disease, with focus on adaptive immunity and anatomical sites of action. We also discuss potential roles of stromal cells.
Lateral pelvic lymph node metastasis in T2 low rectal cancer: is TME alone sufficient for cure?
Authors: Ouchi Akira , Inoue Manabu , Sato Yusuke , Takamizawa Yasuyuki , Kinoshita Takashi , Moritani Konosuke , Komori Koji , Tsukamoto Shunsuke , Shimizu Yasuhiro , Kanemitsu Yukihide
Published: February 2023

Background

Some patients with even T2 low rectal cancer are known to develop lateral pelvic lymph node metastasis. This study aimed to investigate real-world evidence regarding lateral nodal metastasis on T2 low rectal cancer treatment.

Methods

Consecutive patients with pathological T2 low rectal adenocarcinoma who underwent curative-intent surgery between January 2007 and December 2015 at two Japanese cancer centres dedicated to lateral pelvic lymph node dissection were identified and included in the analysis. Lateral pelvic lymph node metastasis was defined as pathologically confirmed metastatic lateral pelvic lymph node or lateral-local recurrence after primary surgery.

Results

A total of 215 consecutive patients, including 101 and 114 patients who did and did not undergo bilateral lateral pelvic lymph node dissection, were included in the analysis. Overall, 19 (8.8%) patients had lateral pelvic lymph node metastasis, including 13 with pathologically confirmed metastatic lateral pelvic lymph node and six with lateral-local recurrence. A total of 10 (4.7%) patients had local recurrence, including six with lateral-local recurrence, two with central-local recurrence and two with anastomotic recurrence. Five/7-year cumulative risks of lateral-local recurrence in patients with and without lateral pelvic lymph node dissection were 1.1/1.1% and 3.9/5.2%, respectively.

Conclusion

The problem of the relatively high rate of lateral local recurrence remains in treating T2 low rectal cancer with only total mesorectal excision. The selection of high-risk patients of lateral pelvic lymph node metastasis and the indication of additional treatment in T2 low rectal cancer should be discussed further.
What do ultraproducts remember about the original structures?
Authors: Towsner Henry
Published: February 2023

We describe a syntactic method for taking proofs that use ultraproducts and translating them into direct, constructive proofs.
Cognitive Load Influences Drop Jump Landing Mechanics During Cognitive-Motor-Simulated Shooting
Authors: McCarren Gillian , Chaput Meredith , Grooms Dustin R , Criss Cody R , Buckley Sean , Brazalovich Philip , Yom Jae , Simon Janet E
Published: February 2023

Introduction

Military duties require immense cognitive-motor multitasks that may predispose soldiers to musculoskeletal injury. Most cognitive challenges performed in the research laboratory are not tactical athlete specific, limiting generalizability and transferability to in-field scenarios. The purpose of this study was to determine the impact of a cognitive-motor multitask (forward drop jump landing while simultaneously performing simulated shooting) on knee kinetics and kinematics.

Methods

Twenty-four healthy collegiate Reserve Officer’s Training Corps members (18 males and 6 females, 20.42 ± 1.28 years, 174.54 ± 10.69 cm, 78.11 ± 14.96 kg) volunteered, and knee kinetics and kinematics were assessed between baseline and cognitive-loaded conditions. Repeated measures ANOVAs were conducted for each dependent variable with the within-subject factor of condition (baseline vs. cognitive load).

Results

Univariate ANOVAs indicated that knee flexion angle at initial contact (IC) (decreased 6.07°; d = 3.14), knee flexion displacement (increased 6.78°; d = 1.30), knee abduction angle at IC (increased 2.3°; d = 1.46), peak knee abduction angle (increased 3.04°; d = 0.77), and peak vertical ground reaction force (increased 0.81 N/kg; d = 2.13) were significant between conditions (P < .001). Therefore, cognitive load resulted in decreased knee flexion and increased knee abduction angle at IC and greater peak vertical ground reaction force, all factors commonly associated with knee injury risk. Peak knee flexion angle and knee abduction displacement were not significant between conditions (P > .05).

Conclusions

Cognitive challenge induced knee landing biomechanics commonly associated with injury risk. Injury risk screening or return-to-training or duty assessments in military personnel might consider both baseline and cognitive conditions.
Rates and Predictors of Surgery for Lumbar Disc Herniation Between the Military and Civilian Health Care Systems
Authors: Anderson Ashley B , Watson Nora L , Pisano Alfred J , Neal Christopher J , Fredricks Donald J , Helgeson Melvin D , Brooks Daniel I , Wagner Scott C
Published: February 2023

Study Design

Retrospective review (level of evidence III).

Objective

Surgical care patterns for lumbar disc herniation (LDH), a common musculoskeletal condition of high relevance to the Military Health System (MHS), have not been described or compared across the direct care and purchased care MHS components. This study aimed to describe surgery rates in MHS beneficiaries who were diagnosed with LDH in direct care versus purchased care and to evaluate characteristics associated with the location of surgery. Differences in care patterns for LDH may suggest unexpected variation within the centrally managed MHS.

Methods

We described 1-year rates of surgery among beneficiaries who were diagnosed with LDH in direct care versus purchased care. Among beneficiaries who were diagnosed in direct care and had surgery, multivariable logistic regression models were used to identify characteristics associated with surgery location.

Results

We identified 726,638 MHS beneficiaries who were diagnosed with LDH in direct care or purchased care during the 9-year study period. One-year surgery rates were 10.1% in beneficiaries who were diagnosed in direct care versus 11.3% in beneficiaries who were diagnosed in purchased care. Among the 7467 patients who were diagnosed in direct care and had surgery within 1 year, characteristics associated with lower probability of surgery in purchased care versus direct care included diagnosing facility type (hospital with a neurosurgery or spine specialty versus clinic (odds ratio [OR], 0.12 (95% CI, 0.10-0.15)), Navy versus Army (OR, 0.24 (95% CI, 0.21-0.28)), and diagnosing facility specialty (Medical Expense and Performance Reporting System) (surgical care (OR, 0.33 (95% CI, 0.27-0.40)) and orthopedic care (OR, 0.39 (95% CI, 0.33-0.46)) versus primary care. The presence of comorbidities was associated with higher probability of surgery in purchased care versus direct care (OR, 1.20 (95% CI, 1.06-1.36)).

Conclusions

The 1-year rate of surgery for LDH was modestly higher in beneficiaries who were diagnosed in purchased care versus direct care. Among patients who were diagnosed in direct care, several patient-level and facility-level characteristics were associated with receiving surgery in purchased care, suggesting potentially unexpected variation in care utilization across components of the MHS.
The Canadian Longitudinal Study on Aging: A Vehicle for Research on Aging in Older Veterans
Authors: Wolfson Christina , Gauvin Danielle E , Schulz Juliana , Magalhaes Sandra , Tansey Catherine M , Feinstein Anthony , Aiken Alice , Scarfo Brittany , Middleton Jason , Raina Parminder , VanTil Linda , Molnar-Szakacs Istvan
Published: February 2023

Introduction

Research on the health of older Veterans in Canada is an emerging area. Few population-based studies in Canada have included older Veterans as a specific group of interest. This paper describes a cohort of self-identified Veterans within the Canadian Longitudinal Study on Aging (CLSA).

Materials and Methods

Using data from the CLSA baseline assessment (2011-2015), we describe sociodemographic and health characteristics along with military-related variables in a cohort of Veterans in Canada. We also estimate the number of Canadian and non-Canadian Veterans living in Canada at the time of the CLSA baseline data collection.

Results

We estimate that at the CLSA baseline, there were 718,893 (95% confidence interval [CI], 680,033-757,110) Canadian Veterans and 185,548 (95% CI, 165,713-205,100) non-Canadian Veterans aged 45-85 years living in Canada. Veterans were older and predominantly male compared to non-Veterans in the CLSA. Following age and sex adjustment, the distribution of sociodemographic and health characteristics was similar across all groups. The majority (> 85%) of participants in each comparison group reported self-rated general and mental health as excellent, very good, or good. Following age and sex adjustment, most characteristics across groups remained similar. One exception was mental health, where a greater proportion of Veterans screened positive for depression and anxiety relative to non-Veterans.

Conclusions

Using CLSA baseline data, we estimate the number of older Veterans in Canada and present descriptive data that highlight interesting differences and similarities between Veterans and non-Veterans living in Canada. Canadian and non-Canadian Veterans in the CLSA are presented separately, with the latter group having not been previously studied in Canada. This paper presents a snapshot of a cohort of self-identified Veterans within the CLSA at study baseline and highlights the potential of the CLSA as a vehicle for studying the aging Veteran population in Canada for years to come.
Multiplane lensing in wave optics
Authors: Feldbrugge Job
Published: February 2023

Wave effects in lensing form a rich phenomenon at the intersection of classical caustic singularities and quantum interference, yet are notoriously difficult to model. Due to a large number of recently observed pulsars and fast radio bursts in radio astronomy and the prospected increase in sensitivity of gravitational wave detectors, wave effects have already been observed in plasma lensing and will be observed in gravitational lensing in the near future. The interference fringes are sensitive to physical parameters, which cannot be inferred from geometric optics. In particular, for multiplane lensing, the pattern depends on the redshifts of the lens planes. I present a new method to define and efficiently evaluate multiplane lensing of coherent electromagnetic waves by plasmas and gravitational lenses in polynomial time. This method will allow the use of radio and gravitational-wave sources to probe our universe in novel ways.
Copper-induced aggregation of IgG: a potential driving force for the formation of circulating protein aggregates
Authors: Saporito-Magriña Christian , Facio María Laura , Lopez-Montañana Lila , Pagano Guadalupe , Repetto Marisa Gabriela
Published: February 2023

Copper is a highly reactive element involved in a myriad of biological reactions. Thus, while essential for mammalian cells, its concentrations must be kept in check in order to avoid toxicity. This metal participates in redox reactions and may exacerbate oxidative stress in aerobic organisms. Nonetheless, the actual driving force of copper-induced cell death is yet unknown. Likely, free copper ions may target different biomolecules that are crucial for the proper functioning of an organism. In this work, we show that free copper induces protein aggregation in serum. The wide set of proteins present in these biological samples are not equally prone to copper-induced aggregation and some, such as albumin, are highly resistant, whereas γ-globulins are highly sensitive. The identity of the proteins in the aggregates becomes fairly homogeneous as metal concentrations go as low as 20 μM. The identification of the proteins by mass spectrometry indicates a preponderance of IgG and a minor presence of other different proteins. Therefore, free copper in blood may contribute to the formation of circulating protein aggregates with a core of IgG. This may impact health not only due to the activity of aggregated IgG but also due to the many proteins co-aggregated. Understanding whether the γ-globulin core and the heterogeneous subgroup of proteins elicit differential responses in the organisms requires further research.
Housing, the credit market, and unconventional monetary policies: from the sovereign crisis to the great lockdown
Authors: Ghiaie Hamed
Published: February 2023

This article evaluates the interactions between housing, the credit market, and the ECB’s asset purchase program (APP) from 2015 until 2020 and then in the course of the ECB’s pandemic emergency purchase program (PEPP) in 2020. The model is calibrated for the euro area. The findings illustrate the way in which macrohousing channels affect bank portfolio rebalancing which is the main channel for asset purchases to influence the economy. The results show that asset purchasing performs better during a crisis, particularly if it is conducted for an appropriate extent of time. The findings suggest that the PEPP alone is not sufficient to accelerate recovery. As a result, further actions such as timely targeted fiscal policies are required to step up recovery. However, to protect the financial sector, the PEPP should be extended until the Covid-19 crisis phase is over.
Effectiveness of Maternal Influenza Vaccination in Peru PRIME Cohort
Authors: Owusu Daniel , Dawood Fatimah S , Azziz-Baumgartner Eduardo , Tinoco Yeny , Soto Giselle , Gonzalez Oswaldo , Cabrera Santiago , Florian Richard , Llajaruna Edwin , Hunt Danielle Rentz , Wesley Meredith G , Yau Tat , Arriola Carmen S
Published: February 2023

Background

Few studies have examined influenza vaccine effectiveness (VE) among women during pregnancy in middle-income countries. We used data from a prospective cohort of women who were pregnant in Peru to estimate effectiveness of the 2018 Southern Hemisphere influenza vaccine.

Methods

Women at <28 weeks gestation were enrolled from 4 tertiary level hospitals in Lima, Peru at the start of the 2018 influenza season and followed until the end of their pregnancies. Participants had mid-turbinate nasal swabs collected and tested for influenza by reverse-transcription polymerase chain reaction (RT-PCR) with onset of ≥1 of myalgia, cough, runny nose or nasal congestion, sore throat, or difficulty breathing. Time-varying Cox proportional hazard regression models were used to estimate the risk of RT-PCR-confirmed influenza infection after adjusting for inverse probability treatment weight.

Results

We followed 1896 women for a median of 127 days (interquartile range [IQR], 86–174). Participants had a median age of 29 years (IQR, 24–34). Among the 1896 women, 49% were vaccinated with the 2018 influenza vaccine and 1039 (55%) developed influenza-like illness, 76 (7%) of whom had RT-PCR-confirmed influenza. Incidence rates of RT-PCR-confirmed influenza were 36.6 and 15.3 per 100 000 person-days among women who were unvaccinated and vaccinated, respectively. Adjusted influenza VE was 22% (95% confidence interval, −64.1% to 62.9%).

Conclusions

Participants vaccinated against influenza had more than 50% lower incidence of RT-PCR-confirmed influenza illness. Although the VE estimated through propensity weight-adjusted time-varying Cox regression did not reach statistical significance, our findings provide additional evidence about the value of maternal influenza vaccination in middle-income countries.
Changing Epidemiology of Carbapenemases Among Carbapenem-Resistant Enterobacterales From United States Hospitals and the Activity of Aztreonam-Avibactam Against Contemporary Enterobacterales (2019–2021)
Authors: Sader Helio S , Mendes Rodrigo E , Carvalhaes Cecilia G , Kimbrough John H , Castanheira Mariana
Published: February 2023

Background

As the frequency of metallo-β-lactamase (MBL)-producing Enterobacterales is increasing worldwide, effective antimicrobials to treat the infections caused by these organisms are urgently needed.

Methods

The activity of aztreonam-avibactam and comparators were evaluated against 27 834 Enterobacterales isolates collected from 74 US medical centers in 2019–2021. Isolates were susceptibility tested by broth microdilution. An aztreonam-avibactam pharmacokinetic/pharmacodynamic breakpoint of ≤8 mg/L was applied for comparison. Antimicrobial susceptibility and the frequency of key resistance phenotypes were assessed then stratified by year and infection type. Carbapenem-resistant Enterobacterales (CRE) were screened for carbapenemase (CPE) genes by whole genome sequencing.

Results

Aztreonam-avibactam inhibited >99.9% of Enterobacterales at ≤8 mg/L. Only 3 isolates (0.01%) had an aztreonam-avibactam minimum inhibitory concentration (MIC) >8 mg/L. The CRE rates were 0.8%, 0.9%, and 1.1% in 2019, 2020, and 2021, respectively; 99.6% (260 of 261) of CRE isolates were inhibited at an aztreonam-avibactam MIC of ≤8 mg/L. The CRE susceptibility to meropenem-vaborbactam decreased from 91.7% in 2019 to 83.1% in 2020 and 76.5% in 2021 (82.1% overall). The CRE, multidrug-resistant, and extensively drug-resistant phenotypes were markedly higher among isolates from pneumonia compared with other infections. The most common carbapenemase among CRE was Klebsiella pneumoniae carbapenemase (65.5% of CRE), followed by New Delhi metallo-β-lactamase (11.1%), oxacillinase (OXA)-48-like (4.6%), Serratia marcescens enzyme (2.3%), and imipenemase (1.5%). Among non-CPE-producing CRE isolates (n = 44; 16.9% of CRE), 97.7% were inhibited at ≤8 mg/L aztreonam-avibactam and 85.4% were meropenem-vaborbactam susceptible.

Conclusions

The frequencies of MBL and OXA-48-type producers increased markedly. Aztreonam-avibactam demonstrated potent and consistent activity against Enterobacterales across infection types and over time.
Missed Opportunities in the Diagnosis of Tuberculosis Meningitis
Authors: Simmons Niamh , Olsen Margaret A , Buss Joanna , Bailey Thomas C , Mejia-Chew Carlos
Published: February 2023

Background

Tuberculosis meningitis (TBM) has high mortality and morbidity. Diagnostic delays can impact TBM outcomes. We aimed to estimate the number of potentially missed opportunities (MOs) to diagnose TBM and determine its impact on 90-day mortality.

Methods

This is a retrospective cohort of adult patients with a central nervous system (CNS) TB International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) diagnosis code (013*, A17*) identified in the Healthcare Cost and Utilization Project, State Inpatient and State Emergency Department (ED) Databases from 8 states. Missed opportunity was defined as composite of ICD-9/10 diagnosis/procedure codes that included CNS signs/symptoms, systemic illness, or non-CNS TB diagnosis during a hospital/ED visit 180 days before the index TBM admission. Demographics, comorbidities, admission characteristics, mortality, and admission costs were compared between those with and without a MO, and 90-day in-hospital mortality, using univariate and multivariable analyses.

Results

Of 893 patients with TBM, median age at diagnosis was 50 years (interquartile range, 37–64), 61.3% were male, and 35.2% had Medicaid as primary payer. Overall, 407 (45.6%) had a prior hospital or ED visit with an MO code. In-hospital 90-day mortality was not different between those with and without an MO, regardless of the MO coded during an ED visit (13.7% vs 15.2%, P = .73) or a hospitalization (28.2% vs 30.9%, P = .74). Independent risk of 90-day in-hospital mortality was associated with older age, hyponatremia (relative risk [RR], 1.62; 95% confidence interval [CI], 1.1–2.4; P = .01), septicemia (RR, 1.6; 95% CI, 1.03–2.45; P = .03), and mechanical ventilation (RR, 3.4; 95% CI, 2.25–5.3; P < .001) during the index admission.

Conclusions

Approximately half the patients coded for TBM had a hospital or ED visit in the previous 6 months meeting the MO definition. We found no association between having an MO for TBM and 90-day in-hospital mortality.
Application of Phage Therapy in a Case of a Chronic Hip-Prosthetic Joint Infection due toPseudomonas aeruginosa: An Italian Real-Life Experience andIn VitroAnalysis
Authors: Cesta Novella , Pini Marco , Mulas Tiziana , Materazzi Alessandro , Ippolito Ernesto , Wagemans Jeroen , Kutateladze Mzia , Fontana Carla , Sarmati Loredana , Tavanti Arianna , Lavigne Rob , Andreoni Massimo , Di Luca Mariagrazia
Published: February 2023

Background

Prosthetic joint infection (PJI) caused by Pseudomonas aeruginosa represents a severe complication in orthopedic surgery. We report the case of a patient with chronic PJI from P. aeruginosa successfully treated with personalized phage therapy (PT) in combination with meropenem.

Methods

A 62-year-old woman was affected by a chronic right hip prosthesis infection caused by P. aeruginosa since 2016 . The patient was treated with phage Pa53 (I day 10 mL q8h, then 5 mL q8h via joint drainage for 2 weeks) in association with meropenem (2gr q12h iv) after a surgical procedure. A 2-year clinical follow up was performed. An in vitro bactericidal assay of the phage alone and in combination with meropenem against a 24-hour-old biofilm of bacterial isolate was also carried out.

Results

No severe adverse events were observed during PT. Two years after suspension, there were no clinical signs of infection relapse, and a marked leukocyte scan showed no pathological uptake areas. In vitro studies showed that the minimum biofilm eradicating concentration of meropenem was 8 µg/mL. No biofilm eradication was observed at 24 hours incubation with phages alone (108 plaque-forming units [PFU]/mL). However, the addition of meropenem at suberadicating concentration (1 µg/mL) to phages at lower titer (103 PFU/mL) resulted in a synergistic eradication after 24 hours of incubation.

Conclusions

Personalized PT, in combination with meropenem, was found to be safe and effective in eradicating P. aeruginosa infection. These data encourage the development of personalized clinical studies aimed at evaluating the efficacy of PT as an adjunct to antibiotic therapy for chronic persistent infections.
The Back Pain Consortium (BACPAC) Research Program Data Harmonization: Rationale for Data Elements and Standards
Authors: Batorsky Anna , Bowden Anton E , Darwin Jessa , Fields Aaron J , Greco Carol M , Harris Richard E , Hue Trisha F , Kakyomya Joseph , Mehling Wolf , O’Neill Conor , Patterson Charity G , Piva Sara R , Sollmann Nico , Toups Vincent , Wasan Ajay D , Wasserman Ronald , Williams David A , Vo Nam V , Psioda Matthew A , McCumber Micah
Published: February 2023

Objective

One aim of the Back Pain Consortium (BACPAC) Research Program is to develop an integrated model of chronic low back pain that is informed by combined data from translational research and clinical trials. We describe efforts to maximize data harmonization and accessibility to facilitate Consortium-wide analyses.

Methods

Consortium-wide working groups established harmonized data elements to be collected in all studies and developed standards for tabular and nontabular data (eg, imaging and omics). The BACPAC Data Portal was developed to facilitate research collaboration across the Consortium.

Results

Clinical experts developed the BACPAC Minimum Dataset with required domains and outcome measures to be collected by use of questionnaires across projects. Other nonrequired domain-specific measures are collected by multiple studies. To optimize cross-study analyses, a modified data standard was developed on the basis of the Clinical Data Interchange Standards Consortium Study Data Tabulation Model to harmonize data structures and facilitate integration of baseline characteristics, participant-reported outcomes, chronic low back pain treatments, clinical exam, functional performance, psychosocial characteristics, quantitative sensory testing, imaging, and biomechanical data. Standards to accommodate the unique features of chronic low back pain data were adopted. Research units submit standardized study data to the BACPAC Data Portal, developed as a secure cloud-based central data repository and computing infrastructure for researchers to access and conduct analyses on data collected by or acquired for BACPAC.

Conclusions

BACPAC harmonization efforts and data standards serve as an innovative model for data integration that could be used as a framework for other consortia with multiple, decentralized research programs.
Lying for Trump? Elite Cue-Taking and Expressive Responding on Vote Method
Authors: Shino Enrijeta , Smith Daniel A , Uribe Laura
Published: February 2023

Might elite cues affect how we vote? Extant literature focuses on effects of elite cues on candidate evaluation or policy preference, but we know little about how they might affect vote method preferences. Drawing on a large survey of validated Florida voters, including those who regularly vote by mail, we find that retrospective and prospective misreporting of vote method prior to the 2020 General Election was driven primarily by support for Trump. The president’s supporters who were most politically aware were most likely to disavow their own voting by mail and misreport their anticipated vote method in the November election. Understanding the effects—and limits—of elite cues on the politicization of self-reported political behavior has important implications for pollsters and campaigns, election administrators, voters, and the broader democratic electoral process.
The Differential Impacts of Contingent Employment on Fertility: Evidence from Australia
Authors: Wooden Mark , Trinh Trong-Anh , Mooi-Reci Irma
Published: February 2023

Many studies have reported evidence of negative associations between fixed-term contract employment and fertility. With few exceptions, these studies assume that employment status is exogenous and thus results are likely biased. Furthermore, previous research has mostly not considered whether the effects of employment status on fertility might vary with other worker characteristics. We draw on nineteen years of data from the Household, Income and Labour Dynamics in Australia Survey to investigate the causal effect of contingent forms of employment (including both fixed-term and casual employment) on first births, and how that effect varies with selected worker characteristics. The issue of endogeneity is addressed through the use of instrumental variables estimation. Our main finding is that both fixed-term contracts and casual employment lead to a significantly lower probability of first births among men, with the effect of fixed-term contracts being almost as twice as large as the effect of casual employment. We also find that these negative fertility effects vary with workers’ education, occupational status, country of origin, age, and relationship status. In the case of women, one of the instruments fails to satisfy the exclusion restriction, suggesting endogeneity remains a concern when analyzing female fertility outcomes.