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The annual increase of waste activated sludge (WAS) has become an urgent problem to be solved in sewage plants worldwide. Anaerobic digestion (AD) of WAS is an attractive choice to maximize the resource utilization rate. Nevertheless, the disintegration of sludge complex polymers is difficult, resulting in a low bioconversion rate. Potassium ferrate (PF), as a green oxidant with strong oxidizing property, has attracted great attention in WAS pretreatment recently. The effects of PF pretreatment on WAS hydrolysis and its dosage-response on methane production were investigated in the present study. Results show that as PF dosage raise from 0 to 50 g-K 2 FeO 4 / kg-TS (total solids), the methane yield enhanced significantly by 40.3% from 0.083 to 0.12 L/g-VS added (volatile solids). Nevertheless, the further increase in PF dosage resulted in decreased methane production. Especially with the PF dosage of 500 g-K 2 FeO 4 / kg-TS, methane production is even slightly lower than the control reactor without PF oxidation. The mechanism analysis showed that although the dissolution of polysaccharides and proteins was enhanced with the high dosage of PF, the accompanying released humic-like substances and high concentration of ferric ions should be the main reasons inhibiting methane production.

To improve the dose efficiency of K 2 FeO 4 in waste activated sludge (WAS) treatment, pH regulation on K 2 FeO 4 pretreatment and acidogenic fermentation was investigated. Four pretreatments were compared, i.e. pH3 + 50 g/kg-TS, pH10 + 50 g/kg-TS, neutral pH + 50 g/kg-TS and neutral pH + 100 g/kg-TS (without pH adjustment). The higher short chain fatty acids (SCFAs) yield and phosphorous dissolution rate was found under the condition of pH 10.0. In pH10 + 50 g/kg-TS, the maximum concentration of SCFAs was 5591 mg-COD/L, which yield was 22.6 times higher than that of the neutral pH + 50 g/kg-TS (237 mg COD/L). The acidogenic fermentation period could be shortened to 5 days and acetic acid accounted for 70 % of SCFAs. Furthermore, PO 4 3- -P in the hydrolysate (346.5 mg/L) accounted for 47.59 % of TP, which is easier to be recovered by chemical precipitation. Therefore, a more economical and feasible utilization mode of potassium ferrate was proposed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Point-of-care ultrasound (POCUS) is a growing part of internal medicine training programs. Dedicated POCUS rotations are emerging as a particularly effective tool in POCUS training, allowing for longitudinal learning and emphasizing both psychomotor skills and the nuances of clinical integration. In this descriptive paper, we set out to review the state of POCUS rotations in Canadian Internal Medicine training programs., Results: We identify five programs currently offering a POCUS rotation. These rotations are offered over two to thirteen blocks each year, run over one to four weeks and support one to four learners. Across all programs, these rotations are set up as a consultative service that offers POCUS consultation to general internal medicine inpatients, with some extension of scope to the hospitalist service or surgical subspecialties. The funding model for the preceptors of these rotations is predominantly fee-for-service using consultation codes, in addition to concomitant clinical work to supplement income. All but one program has access to hospital-based archiving of POCUS exams. Preceptors dedicate ten to fifty hours to the rotation each week and ensure that all trainee exams are reviewed and documented in the patient's medical records in the form of a consultation note. Two of the five programs also support a POCUS fellowship. Only two out of five programs have established learner policies. All programs rely on In-Training Evaluation Reports to provide trainee feedback on their performance during the rotation., Conclusions: We describe the different elements of the POCUS rotations currently offered in Canadian Internal Medicine training programs. We share some lessons learned around the elements necessary for a sustainable rotation that meets high educational standards. We also identify areas for future growth, which include the expansion of learner policies, as well as the evolution of trainee assessment in the era of competency-based medical education. Our results will help educators that are endeavoring setting up POCUS rotations achieve success., (© 2022. The Author(s).)

Purpose: To evaluate change in the severity of hypoxic-ischemic encephalopathy (HIE) and associated morbidities between pre- and during COVID-19 pandemic periods in Canada., Methods: We conducted a retrospective cohort study extracting the data from level-3 NICUs participating in Canadian Neonatal Network (CNN). The primary outcome was a composite of death in the first week after birth and/or stage 3 HIE (Sarnat and Sarnat). Secondary outcomes included rate and severity of HIE among admitted neonates, overall mortality, brain injury on magnetic resonance imaging (MRI), neonates requiring resuscitation, organ dysfunction, and therapeutic hypothermia (TH) usage. We included 1591 neonates with gestational age ≥ 36 weeks with HIE during the specified periods: pandemic cohort from April 1st to December 31st of 2020; pre-pandemic cohort between April 1st and December 31st of 2017, 2018, and 2019. We calculated the odds ratio (OR) and confidence intervals (CI)., Results: We observed no significant difference in the primary outcome (15% vs. 16%; OR 1.08; 95%CI 0.78-1.48), mortality in the first week after birth (6% vs. 6%; OR 1.10, 95%CI 0.69-1.75), neonates requiring resuscitation, organ dysfunction, TH usage, or rate of brain injury. In the ad hoc analysis, per 1000 live births, there was an increase in the rate of infants with HIE and TH use., Conclusions: Severity of HIE, associated morbidities, and mortality were not significantly different during the pandemic lockdown compared to a pre-pandemic period in Canada. Anticipated risks and difficulties in accessing healthcare have not increased the mortality and morbidities in neonates with HIE in Canada., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sox17 gene expression is essential for both endothelial and endodermal cell differentiation. To better understand the genetic basis for the expression of multiple Sox17 mRNA forms, we identified and performed CRISPR/Cas9 mutagenesis of two evolutionarily conserved promoter regions (CRs). The deletion of the upstream and endothelial cell-specific CR1 caused only a modest increase in lympho-vasculogenesis likely via reduced Notch signaling downstream of SOX17. In contrast, the deletion of the downstream CR2 region, which functions in both endothelial and endodermal cells, impairs both vascular and endodermal development causing death by embryonic day 12.5. Analyses of 3D chromatin looping, transcription factor binding, histone modification, and chromatin accessibility data at the Sox17 locus and surrounding region further support differential regulation of the two promoters during the development., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

During mitosis, individual microtubules make attachments to chromosomes via a specialized protein complex called the kinetochore to faithfully segregate the chromosomes to daughter cells. Translocation of kinetochores on the lateral surface of the microtubule has been proposed to contribute to high fidelity chromosome capture and alignment at the mitotic midzone, but has been difficult to observe in vivo because of spatial and temporal constraints. To overcome these barriers, we used total internal reflection fluorescence (TIRF) microscopy to track the interactions between microtubules, kinetochore proteins, and other microtubule-associated proteins in lysates from metaphase-arrested Saccharomyces cerevisiae . TIRF microscopy and cryo-correlative light microscopy and electron tomography indicated that we successfully reconstituted interactions between intact kinetochores and microtubules. These kinetochores translocate on the lateral microtubule surface toward the microtubule plus end and transition to end-on attachment, whereupon microtubule depolymerization commences. The directional kinetochore movement is dependent on the highly processive kinesin-8, Kip3. We propose that Kip3 facilitates stable kinetochore attachment to microtubule plus ends through its abilities to move the kinetochore laterally on the surface of the microtubule and to regulate microtubule plus end dynamics., Competing Interests: JT, JW, DS, AM, DD, GB No competing interests declared, (© 2022, Torvi, Wong et al.)

Peripheral T-cell lymphoma (PTCL) is a rare, heterogenous malignancy with dismal outcomes at relapse. Hypomethylating agents (HMA) have an emerging role in PTCL, supported by shared mutations with myelodysplasia (MDS). Response rates to azacitidine in PTCL of follicular helper cell origin are promising. Guadecitabine is a decitabine analogue with efficacy in MDS. In this phase II, single-arm trial, PTCL patients received guadecitabine on days 1-5 of 28-day cycles. Primary end points were overall response rate (ORR) and safety. Translational sub-studies included cell free plasma DNA sequencing and functional genomic screening using an epigenetically-targeted CRISPR/Cas9 library to identify response predictors. Among 20 predominantly relapsed/refractory patients, the ORR was 40% (10% complete responses). Most frequent grade 3-4 adverse events were neutropenia and thrombocytopenia. At 10 months median follow-up, median progression free survival (PFS) and overall survival (OS) were 2.9 and 10.4 months respectively. RHOA G17V mutations associated with improved PFS (median 5.47 vs. 1.35 months; Wilcoxon p = 0.02, Log-Rank p = 0.06). 4/7 patients with TP53 variants responded. Deletion of the histone methyltransferase SETD2 sensitised to HMA but TET2 deletion did not. Guadecitabine conveyed an acceptable ORR and toxicity profile; decitabine analogues may provide a backbone for future combinatorial regimens co-targeting histone methyltransferases., (© 2022. The Author(s).)

This study explores the natural history of vestibular, trigeminal and lower cranial nerve schwannomas (VS, TS, LCNS) in patients with Neurofibromatosis type 2 (NF2), to understand how pathogenic variants (PVs) of the NF2 gene affect tumour burden and growth rate, via a retrospective analysis of a UK NF2 centre database and imaging. VS, TS and LCNS location and size were measured in accordance with a standardised protocol. PVs were categorised in accordance with the UK NF2 Genetic Severity Score (GSS). 153 patients (age 5-82) had 458 schwannomas, of which 362 were previously untreated comprising: 204 VS, 93 TS, and 65 LCNS (IX, X, XI). 322 schwannomas had sequential imaging allowing growth rate analysis with a mean follow-up of 45 months. VS were universally present, and bilateral in 146/153 cases. 65% of tumours grew >2 mm during the study period at mean rate 2.0 mm/year. Significant association was found between increasing GSS and growth rate. TS occurred in 66/153 patients (bilateral in 27/153); 31% of tumours showed growth (mean 1.8 mm/yr). Significant increase in tumour prevalence was noted with increasing GSS. LCNS were found in 47/153 patients (bilateral in 19/153); 27% of tumours showed growth (mean 1.9 mm/yr). The trend for increased prevalence with increasing GSS did not reach significance. VS growth rate was significantly influenced by GSS and they were much more likely to grow than TS and LCNS. TS prevalence also correlated with increasing GSS., (© 2022. The Author(s), under exclusive licence to European Society of Human Genetics.)

Objective: To compare short term respiratory outcomes in preterm infants treated with bovine lipid extract surfactant or poractant alfa., Study Design: Prospective comparative effectiveness cohort study of infants <32 weeks' gestational age requiring surfactant in thirteen centers. Each center provided bovine lipid extract surfactant for a set period of time in the year 2019 and then changed to poractant alfa for the remainder of the year. The primary outcome was total duration of respiratory support., Result: 968 infants were included. 494 received bovine lipid extract surfactant and 474 received poractant alfa. No difference was observed in the total duration of respiratory support (mechanical ventilation or non-invasive) (median 38 vs 40.5 days), need to re-dose surfactant, bronchopulmonary dysplasia, survival to discharge, or length of admission., Conclusion: In this pragmatic study, we did not identify any difference in short term outcomes between the groups based on the type of surfactant received., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

In the past decades, considerable attention has been directed toward anaerobic digestion (AD), which is an effective biological process for converting diverse organic wastes into biogas, volatile fatty acids (VFAs), biohydrogen, etc. The microbial bioprocessing takes part during AD is of substantial significance, and one of the crucial approaches for the deep and adequate understanding and manipulating it toward different products is process microbiology. Due to highly complexity of AD microbiome, it is critically important to study the involved microorganisms in AD. In recent years, in addition to traditional methods, novel molecular techniques and meta-omics approaches have been developed which provide accurate details about microbial communities involved AD. Better understanding of process microbiomes could guide us in identifying and controlling various factors in both improving the AD process and diverting metabolic pathway toward production of selective bio-products. This review covers various platforms of AD process that results in different final products from microbiological point of view. The review also highlights distinctive interactions occurring among microbial communities. Furthermore, assessment of these communities existing in the anaerobic digesters is discussed to provide more insights into their structure, dynamics, and metabolic pathways. Moreover, the important factors affecting microbial communities in each platform of AD are highlighted. Finally, the review provides some recent applications of AD for the production of novel bio-products and deals with challenges and future perspectives of AD.

Objectives: People experiencing homelessness are at increased risk of SARS-CoV-2 infection. This study reports the point prevalence of SARS-CoV-2 infection during testing conducted at sites serving people experiencing homelessness in Toronto during the first wave of the COVID-19 pandemic. We also explored the association between site characteristics and prevalence rates., Methods: The study included individuals who were staying at shelters, encampments, COVID-19 physical distancing sites, and drop-in and respite sites and completed outreach-based testing for SARS-CoV-2 during the period April 17 to July 31, 2020. We examined test positivity rates over time and compared them to rates in the general population of Toronto. Negative binomial regression was used to examine the relationship between each shelter-level characteristic and SARS-CoV-2 positivity rates. We also compared the rates across 3 time periods (T1: April 17-April 25; T2: April 26-May 23; T3: May 24-June 25)., Results: The overall prevalence of SARS-CoV-2 infection was 8.5% (394/4657). Site-specific rates showed great heterogeneity with infection rates ranging from 0% to 70.6%. Compared to T1, positivity rates were 0.21 times lower (95% CI: 0.06-0.75) during T2 and 0.14 times lower (95% CI: 0.04-0.44) during T3. Most cases were detected during outbreak testing (384/394 [97.5%]) rather than active case finding., Conclusion: During the first wave of the pandemic, rates of SARS-CoV-2 infection at sites for people experiencing homelessness in Toronto varied significantly over time. The observation of lower rates at certain sites may be attributable to overall time trends, expansion of outreach-based testing to include sites without known outbreaks, and/or individual site characteristics., (© 2021. The Author(s).)

The hepatitis C virus (HCV) is a common cause of chronic liver disease and liver cancer worldwide. Despite advances in curative therapies for HCV, the incidence of new infections is not decreasing at the expected rate to hit the World Health Organization (WHO) target for the elimination of HCV by 2030. In fact, there are still more new cases of infection in the United States and worldwide than are being cured. The reasons for the rise in new cases include poor access to care and the opioid epidemic. The clinical burden of HCV requires a multimodal approach to eradicating the infection. Vaccination would be an excellent tool to prevent incidence of new infections; however, the genetic diversity of HCV and its ability to generate quasispecies within an infected host make creating a broadly reactive vaccine difficult. Multiple vaccine candidates have been identified, but to date, there has not been a target that has led to a broadly reactive vaccine, though several of the candidates are promising. Additionally, the virus is very difficult to culture and testing candidates in humans or chimpanzees is ethically challenging. Despite the multiple barriers to creating a vaccine, vaccination still represents an important tool in the fight against HCV.

Bronchopulmonary dysplasia (BPD) is the most prevalent and clinically significant complication of prematurity. Accurate identification of at-risk infants would enable ongoing intervention to improve outcomes. Although postnatal exposures are known to affect an infant's likelihood of developing BPD, most existing BPD prediction models do not allow risk to be evaluated at different time points, and/or are not suitable for use in ethno-diverse populations. A comprehensive approach to developing clinical prediction models avoids assumptions as to which method will yield the optimal results by testing multiple algorithms/models. We compared the performance of machine learning and logistic regression models in predicting BPD/death. Our main cohort included infants <33 weeks' gestational age (GA) admitted to a Canadian Neonatal Network site from 2016 to 2018 ( n = 9,006) with all analyses repeated for the <29 weeks' GA subcohort ( n = 4,246). Models were developed to predict, on days 1, 7, and 14 of admission to neonatal intensive care, the composite outcome of BPD/death prior to discharge. Ten-fold cross-validation and a 20% hold-out sample were used to measure area under the curve (AUC). Calibration intercepts and slopes were estimated by regressing the outcome on the log-odds of the predicted probabilities. The model AUCs ranged from 0.811 to 0.886. Model discrimination was lower in the <29 weeks' GA subcohort (AUCs 0.699-0.790). Several machine learning models had a suboptimal calibration intercept and/or slope (k-nearest neighbor, random forest, artificial neural network, stacking neural network ensemble). The top-performing algorithms will be used to develop multinomial models and an online risk estimator for predicting BPD severity and death that does not require information on ethnicity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Khurshid, Coo, Khalil, Messiha, Ting, Wong and Shah.)

Competing Interests: The authors report no conflicts of interest.

Ultrashort echo time (UTE) sequences can image tissues with transverse T  2 /T  2 * relaxations too short to be efficiently observed on routine clinical MRI sequences, such as the vertebral body cartilaginous endplate (CEP). Here, we describe a 3D adiabatic inversion-recovery-prepared fat-saturated ultrashort echo time (3D IR-FS-UTE) sequence to highlight the CEP of vertebral bodies in comparison to the intervertebral disc (IVD) and bone marrow fat (BF) at 3 T. The IR-FS-UTE sequence used a 3D UTE sequence combined with an adiabatic IR preparation pulse centered in the middle of the water and fat peaks, while a fat saturation module was used to suppress the signal from fat. A slab-selective half pulse was used for signal excitation, and a 3D center-out cones trajectory was used for more efficient data sampling. The 3D IR-FS-UTE sequence was applied to an ex vivo human spine sample, as well as the spines of six healthy volunteers and of three patients with back pain. Bright continuous lines representing signal from CEP were found in healthy IVDs. The measured contrast-to-noise ratio was 18.5 ± 4.9 between the CEP and BF, and 20.3 ± 4.15 between the CEP and IVD for the six volunteers. Abnormal IVDs showed CEP discontinuity or irregularity in the sample and patient studies. In conclusion, the proposed 3D IR-FS-UTE sequence is feasible for imaging the vertebral body's CEP in vivo with high contrast., (© 2021 John Wiley & Sons, Ltd.)

Competing Interests: The authors declare that they have no conflict of interest.

Objective: The causes of protein malnutrition and body composition changes in chronic kidney disease (CKD) are poorly understood. Alterations to metabolic rate caused by CKD may be a contributor. Using the doubly labeled water technique and indirect calorimetry, we set out to determine whether reduced glomerular filtration rate is associated with alterations to total energy expenditure (TEE) and resting energy expenditure (REE). We also aimed to determine whether TEE in patients with CKD can be easily predicted from a physical activity questionnaire., Methods: In a prospective, observational study we evaluated 80 patients (52 men; mean age 56.7 ± 16.2 years) with CKD ranging from stage 1 to stage 5 with estimated glomerular filtration rate (eGFR) calculated by the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). TEE was measured using doubly labeled water isotope excretion over 14 days (TEE DLW ), REE by indirect calorimetry (REE IndirectCal ) and physical activity level using the Stanford 7-day recall questionnaire., Results: eGFR did not correlate with TEE DLW and REE IndirectCal . Findings with weight-adjusted energy measures were similar. REE IndirectCal and TEE DLW were significantly lower in patients whose eGFR was <50 mL/min/1.73 m 2 and those with higher levels. There were similar findings with respect to weight-adjusted energy measures. In multivariable analysis, age, sex, and weight were independent predictors of TEE DLW and REE IndirectCal . eGFR did not predict TEE or REE in either of these models., Conclusion: There was no direct relationship between reduced renal function and metabolic rate. Differences in energy metabolism at lower levels of glomerular filtration rate are more likely to be due to factors such as age, body composition, and physical activity., (Copyright © 2020. Published by Elsevier Inc.)

A catalyst-controlled enantiodivergent bromolactonization of olefinic acids has been developed. Quinine-derived amino-amides bearing the same chiral core but different achiral aryl substituents were used as the catalysts. Switching the methoxy substituent in the aryl amide system from meta - to ortho -position results in a complete switch in asymmetric induction to afford the desired lactone in good enantioselectivity and yield. Mechanistic studies, including chemical experiments and density functional theory calculations, reveal that the differences in steric and electronic effects of the catalyst substituent alter the reaction mechanism.

Introduction: Transfer of infants for magnetic resonance imaging (MRI) from the neonatal intensive care unit (NICU) requires exposure to unfamiliar environments and involve multiple complex human and system interactions, which can compromise patient safety. In situ simulation (ISS) offers an opportunity to identify latent safety threats (LSTs) that may occur during this high-risk procedure. Our primary aim was to use ISS to identify modifiable LSTs during the MRI procedure: involving neonatal transport to/from NICU to the MRI and the MRI scan. Secondarily, we compared the overall performance and needs of specialized versus nonspecialized transport personnel., Methods: In situ simulations of the MRI procedure (transport and scan) were performed for 9 months involving specialized and nonspecialized transport personnel. Two simulation scenarios were used, one involving an intubated infant and one nonintubated infant. After each simulation, participants underwent a standardized debriefing and answered questionnaires on safety threats and team function. The results were then used to identify and implement mitigation strategies., Results: Among 10 simulations completed, 7 were by specialized and 3 by nonspecialized teams. In total, 116 LSTs were identified (22 involving medication, 12 equipment, and 82 resources/system issues). Preprocedure deliberation with anticipation/preparedness for patient deterioration, and the need for clinical checklists and protocols were identified as important requirements. After completion of the project, protocols (ie, sedation), checklists (ie, pretransport), and policies (ie, environmental orientation) were adapted to address the gaps., Conclusions: In situ simulations were able to identify important safety risks during transport of neonatal patients from the NICU to the MRI suite, informing changes in MRI transport policy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Society for Simulation in Healthcare.)

A facile, efficient, and chemoselective synthesis of allylic amides has been developed. Allyl bromides were used as the precursors activated by silver triflate. A Ritter-type reaction readily proceeded to give various allyl amides under mild conditions. The reaction protocol was also applicable to different nucleophilic partners to give a wide range of allyl-substituted products in the absence of a base.

Bromofunctionalizations of olefins are an important class of chemical transformations. N -Bromoimide reagents are commonly used in these reactions but catalysts and chlorinated solvents are often employed to achieve a reasonable reaction rate. In this report, we present a solvent and catalyst-free bromofunctionalization of olefins using mechanical force., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Competing Interests: The authors declare that they have no conflict of interest.

Magnetic properties of molecules such as magnetizabilities represent second order derivatives of the energy with respect to external perturbations. To avoid the need for analytic second derivatives and thereby permit evaluation of the performance of methods where they are not available, a new implementation of quantum chemistry calculations in finite applied magnetic fields is reported. This implementation is employed for a collection of small molecules with the aug-cc-pVTZ basis set to assess orbital optimized (OO) MP2 and a recently proposed regularized variant of OOMP2, called κ -OOMP2. κ -OOMP2 performs significantly better than conventional second order Møller-Plesset (MP2) theory, by reducing MP2's exaggeration of electron correlation effects. As a chemical application, we revisit an old aromaticity criterion called magnetizability exaltation. In lieu of empirical tables or increment systems to generate references, we instead use straight chain molecules with the same formal bond structure as the target cyclic planar conjugated molecules. This procedure is found to be useful for qualitative analysis, yielding exaltations that are typically negative for aromatic species and positive for antiaromatic molecules. One interesting species, N 2 S 2 , shows a positive exaltation despite having aromatic characteristics.

Conventional magnetic resonance imaging (MRI) is not capable of detecting signal from the deep cartilage due to its short transverse relaxation time (T2). Moreover, several quantitative MRI techniques are significantly influenced by the magic angle effect. The combinations of ultrashort echo time (UTE) MRI with magnetization transfer (UTE-MT) and Adiabatic T 1ρ (UTE-AdiabT 1ρ ) imaging allow magic angle-insensitive assessments of all regions of articular cartilage. The purpose of this study was to investigate the correlations between quantitative three-dimensional UTE MRI biomarkers and mechanical properties of human tibiofemoral cartilage specimens. In total, 40 human tibiofemoral cartilage specimens were harvested from three male and four female donors (64 ± 18 years old). Cartilage samples were scanned using a series of quantitative 3D UTE Cones T 2 * (UTE-T 2 *), T 1 (UTE-T 1 ), UTE-AdiabT 1ρ , and UTE-MT sequences in a standard knee coil on a clinical 3T scanner. UTE-MT data were acquired with a series of MT powers and frequency offsets to calculate magnetization transfer ratio (MTR), as well as macromolecular fraction (MMF) and macromolecular T 2 (T 2 mm) through modeling. Cartilage stiffness and Hayes elastic modulus were measured using indentation tests. Correlations of 3D UTE Cones MRI measurements in the superficial layer, deep layer, and global regions of interest (ROIs) with mechanical properties were investigated. Cartilage mechanical properties demonstrated highest correlations with UTE measures of the superficial layer of cartilage. AdiabT 1ρ , MTR, and MMF in superficial layer ROIs showed significant correlations with Hayes elastic modulus (p < 0.05, R = -0.54, 0.49, and 0.66, respectively). These UTE measures in global ROIs showed significant, though slightly lower, correlations with Hayes elastic modulus (p < 0.05, R = -0.37, 0.52, and 0.60, respectively). Correlations between other UTE MRI measurements (T 2 *, T 1 , and T 2 mm) and mechanical properties were non-significant. The 3D UTE-AdiabT 1ρ and UTE-MT sequences were highlighted as promising surrogates for non-invasive assessment of cartilage mechanical properties. MMF from UTE-MT modeling showed the highest correlations with cartilage mechanics., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: The purpose of this study was to investigate the feasibility of ultrashort echo time quantitative susceptibility mapping (UTE-QSM) for assessment of hemosiderin deposition in the joints of hemophilic patients., Methods: The UTE-QSM technique was based on three sets of dual-echo 3D UTE Cones data acquired with TEs of 0.032/2.8, 0.2/3.6, and 0.4/4.4 ms. The images were processed with iterative decomposition of water and fat with echo asymmetry and least-squares estimation to estimate the B 0 field map in the presence of fat. Then, the projection onto dipole field (PDF) algorithm was applied to acquire a local field map generated by tissues, followed by application of the morphology-enabled dipole inversion (MEDI) algorithm to estimate a final susceptibility map. Three healthy volunteers and three hemophilic patients were recruited to evaluate the UTE-QSM technique's ability to assess hemosiderin in the knee or ankle joint at 3T. One patient subsequently underwent total knee arthroplasty after the MR scan. The synovial tissues harvested from the knee joint during surgery were processed for histological analysis to confirm iron deposition., Results: UTE-QSM successfully yielded tissue susceptibility maps of joints in both volunteers and patients. Multiple regions with high susceptibility over 1 ppm were detected in the affected joints of hemophilic patients, while no localized regions with high susceptibility were detected in asymptomatic healthy volunteers. Histology confirmed the presence of iron in regions where high susceptibility was detected by UTE-QSM., Conclusion: The UTE-QSM technique can detect hemosiderin deposition in the joint, and provides a potential sensitive biomarker for the diagnosis and prognosis of hemophilic arthropathy., (© 2020 International Society for Magnetic Resonance in Medicine.)

Aims: The aim of this study was to report the incidence of perioperative adverse events occurring in infants undergoing diode laser photocoagulation of retinopathy of prematurity and to identify clinical risk factors that may affect the incidence., Methods: This was a retrospective study of anesthetic and medical records of premature infants who were treated in the neonatal intensive care unit or an operating theater with laser photocoagulation in our institution between January 2014 and December 2019. Infants less than 38 weeks post-menstrual age or less than 2000 grams were considered high risk for complications. Electronic medical records were evaluated for clinical and demographic characteristics, comorbidities, and perioperative complications of anesthesia., Results: Sixty-one infants (39 males, 22 females) underwent 72 laser treatments. The mean gestational age was 25.3 weeks (SD 1.6), and mean birth weight was 730 grams (SD 202). At treatment, the mean postmenstrual age was 37.5 weeks (SD 2.7) and weight was 2320 g (SD 610). Laser therapy was performed in an operating theater in 66 procedures (91.7%) and in the neonatal unit in 6 cases (8.3%). Twenty-nine (40.3%) laser surgeries occurred outside normal week-day daytime operating hours. Intraoperative hypotension occurred in 12 procedures (16.7%) but was not significantly different in high-risk infants (16.1% vs 16.7% OR 0.94 P = .94) or in procedures performed in-hours (16.3% vs 17.2% OR 0.93 P = .91). Post-extubation apnea occurred in 21 procedures (29%) but was not significantly different in high-risk infants (29.0% vs 27.3% OR 0.98 P = .34) or in procedures performed in-hours (27.9% vs 31.1% OR 0.86 P = .77). Infants remained intubated at the end of the procedure in 58 (80.5%) cases and 29 (40.3%) remained ventilated more than 24 hours after the procedure., Conclusion: The incidence of perioperative adverse events was not associated with patient's age, current weight, timing, or location of the procedure. Extubating infants at the end of the procedure is however associated with a high rate of apneas and bradycardia, and consideration should be given to keeping low weight infants undergoing prolonged procedures out-of-hours intubated., (© 2020 John Wiley & Sons Ltd.)

Direct myelin imaging is promising for characterization of multiple sclerosis (MS) brains at diagnosis and in response to therapy. In this study, a 3D inversion recovery-prepared ultrashort echo time cones (IR-UTE-Cones) sequence was used for both morphological and quantitative imaging of myelin on a clinical 3 T scanner. Myelin powder phantoms with different myelin concentrations were imaged with the 3D UTE-Cones sequence and it showed a strong correlation between concentrations and UTE-Cones signals, demonstrating the ability of the UTE-Cones sequence to directly image myelin in the brain. Quantitative myelin imaging with multi-echo IR-UTE-Cones sequences show similar T 2 * values for a D 2 O-exchanged myelin phantom (T 2 * = 0.33 ± 0.04 ms), ex vivo brain specimens (T 2 * = 0.20 ± 0.04 ms) and in vivo healthy volunteers (T 2 * = 0.254 ± 0.023 ms), further confirming the feasibility of 3D IR-UTE-Cones sequences for direct myelin imaging in vivo. In ex vivo MS brain study, signal loss is observed in MS lesions, which was confirmed with histology. For the in vivo study, the lesions in MS patients also show myelin signal loss using the proposed direct myelin imaging method, demonstrating the clinical potential for MS diagnosis. Furthermore, the measured IR-UTE-Cones signal intensities show a significant difference between normal-appearing white matter in MS patients and normal white matter in volunteers, which cannot be found in clinical used T 2 -FLAIR sequences. Thus, the proposed 3D IR-UTE-Cones sequence showed clinical potential for MS diagnosis with the capability of direct myelin detection of the whole brain., (© 2020 John Wiley & Sons, Ltd.)

T-cell lymphoblastic lymphoma/T-cell acute lymphoblastic leukemia (T-LBL/T ALL) is an aggressive hematological malignancy arising from malignant transformation of T-cell progenitors with poor prognosis in adult patients. Outcomes are particularly dismal in the relapsed/refractory setting, and therapeutic options are limited in this context. Genomic profiling has shown frequent aberrations in the JAK-STAT pathway, including recurrent mutations in JAK3 (15%-20% of T-ALL cases), suggesting that JAK kinase inhibition may be a promising therapeutic approach. Activating JAK3 mutations are capable of transforming cytokine-dependent progenitor cells in vitro and causing T-ALL-like disease when expressed in hematopoietic progenitors in vivo. We describe a case of relapsed T-ALL in an adult patient, with two JAK3 activating mutations identified by whole-exome sequencing (WES), leading to hypothesis-based treatment with the JAK1 and JAK3 inhibitor, tofacitinib, following failure of salvage chemotherapy reinduction. Despite the molecularly targeted rationale, tofacitinib did not induce an objective clinical response. Our report suggests that the presence of activating JAK3 mutations does not necessarily confer sensitivity to pharmacological JAK3 inhibition., (© 2020 Wong et al.; Published by Cold Spring Harbor Laboratory Press.)

Competing Interests: None

Background: Point-of-care ultrasound (POCUS) is increasingly used in internal medicine, but a lack of trained faculty continues to limit the spread of POCUS education. Using a framework based on organizational change theories, this study sought to identify barriers and enablers for hospital-based practicing internists to learn and use POCUS in clinical practice., Methods: We invited practicing internists at six North American institutions to participate in an electronic survey on their opinions regarding 39 barriers and enablers., Results: Of the 342 participants invited, 170 participated (response rate 49.3%). The top barriers were lack of training (79%), lack of handheld ultrasound devices (78%), lack of direct supervision (65%), lack of time to perform POCUS during rounds (65%), and lack of quality assurance processes (53%). The majority of participants (55%) disagreed or strongly disagreed with the statement "My institution provides funding for POCUS training." In general, participants' attitudes towards POCUS were favourable, and future career opportunities and the potential for billing were not considered significant factors by our participants in the decision to learn or use POCUS., Conclusions: This survey confirms the perceived importance of POCUS to practicing internists. To assist in closing faculty development gap, interventions should address training, supervision, quality assurance processes, availability of handheld devices, as well as dedicated time to perform POCUS during clinical care.

Background/aims: (1-3)-β-D glucans (BG) are cellular components of yeasts and fungi. Elevated blood levels may be an adjunct in diagnosing invasive fungal infection, though can be high in dialysis patients without fungaemia. BG can also induce false positive signals in endotoxin detection assays (Limulus Amoebocyte Lysate [LAL] assay). We explored the relationship between BG levels, renal impairment, endotoxaemia and inflammation., Methods: We measured serum BG levels, markers of inflammation and blood endotoxin levels in 20 controls, 20 with stages 1-3 chronic kidney disease (CKD), 20 with stages 4-5 CKD, 15 on peritoneal dialysis (PD) and 60 on haemodialysis (HD). Another 30 patients were studied before and after HD initiation., Results: BG levels increased with advancing CKD, being highest in HD patients, 22% of whom had elevated levels (> 80 pg/ml). Levels increased significantly following HD initiation. Levels also correlated positively with CRP, TNFα, IL-6 levels, independently of CKD stage. Blood endotoxin was detectable by LAL assays in 10-53% of the CKD cohort, being most prevalent in the HD group, and correlating positively with BG levels. Adding BG blocking agent to the assay reduced endotoxin detection confining it to only 5% of HD patients. Levels of inflammatory markers were higher in those with detectable endotoxin - whether false- or true positives., Conclusion: BG levels increased with decreasing renal function, being highest in dialysis patients. High BG levels were associated with false positive blood endotoxin signals, and with markers of inflammation, independently of CKD stage. The cause for high BG levels is unknown but could reflect increased gut permeability and altered mononuclear phagocytic system function.

Background: Providing safe and effective sedation to critically ill children is challenging. The assessment, prevention, and treatment of symptoms of iatrogenic withdrawal are critical aspects of sedation practice., Objective: To describe the use of sedative medications in critically ill children at McMaster Children's Hospital., Methods: This retrospective observational study included children admitted over a 12-month period who survived their illness and who received sedation and at least 48 h of invasive ventilation. We collected data from the time of admission to the pediatric intensive care unit to 3 days after discontinuation of sedation., Results: We included 67 children. The median age was 1.6 (interquartile range [IQR] 0.2-6.2) years, and respiratory illnesses were the most common reason for admission (41 [61%]). The children received invasive ventilation for a median of 7 (IQR 4-11) days and sedation for a median of 12 (IQR 6-20) days. Sixty-six children (99%) received an opioid, and all received a benzodiazepine, with median cumulative doses of 14 (IQR 5-27) mg/kg morphine equivalents and 15 (IQR 6-32) mg/kg midazolam equivalents. Dexmedetomidine was given to 31 children (46%), for a median of 8 (IQR 4-12) days. Most children (67%) received sedation after extubation (median duration 7 [IQR 4-14] days). In addition, 32 children (48%) continued to receive sedative medications after transfer to the ward, for a median of 6 (IQR 4-13) days. Forty-two children (63%) had at least one Withdrawal Assessment Tool-1 (WAT-1) score indicative of iatrogenic withdrawal. Children who experienced withdrawal were exposed to more opioids and more benzodiazepines, both per day and overall, and for longer periods., Conclusions: The children in this study were exposed to multiple sedatives, and many continued to receive these medications for an extended period after discontinuation of mechanical ventilation. Iatrogenic withdrawal was common and represents an important opportunity to improve children's recovery after critical illness., Competing Interests: Competing interests: None declared., (2020 Canadian Society of Hospital Pharmacists. All content in the Canadian Journal of Hospital Pharmacy is copyrighted by the Canadian Society of Hospital Pharmacy. In submitting their manuscripts, the authors transfer, assign, and otherwise convey all copyright ownership to CSHP.)

In this work, we have explored the use of a third species during chemical vapor deposition (CVD) to direct thin-film growth to occur exclusively on one surface in the presence of another. Using a combination of density functional theory (DFT) calculations and experiments, including in situ surface analysis, we have examined the use of 4-octyne as a coadsorbate in the CVD of ZrO 2 thin films on SiO 2 and Cu surfaces. At sufficiently high partial pressures of the coadsorbate and sufficiently low substrate temperatures, we find that 4-octyne can effectively compete for adsorption sites, blocking chemisorption of the thin-film precursor, Zr[N(CH 3 C 2 H 5 )] 4 , and preventing growth on Cu, while leaving growth unimpeded on SiO 2 . The selective dielectric-on-dielectric (DoD) process developed herein is fast, totally vapor phase, and does not negatively alter the composition or morphology of the deposited thin film. We argue that this approach to area-selective deposition (ASD) should be widely applicable, provided that suitable candidates for preferential binding can be identified.

Background Signal contamination from long T2 water is a major challenge in direct imaging of myelin with MRI. Nulling of the unwanted long T2 signals can be achieved with an inversion recovery (IR) preparation pulse to null long T2 white matter within the brain. The remaining ultrashort T2 signal from myelin can be detected with an ultrashort echo time (UTE) sequence. Purpose To develop patient-specific whole-brain myelin imaging with a three-dimensional double-echo sliding inversion recovery (DESIRE) UTE sequence. Materials and Methods The DESIRE UTE sequence generates a series of IR images with different inversion times during a single scan. The optimal inversion time for nulling long T2 signal is determined by finding minimal signal on the second echo. Myelin images are generated by subtracting the second echo image from the first UTE image. To validate this method, a prospective study was performed in phantoms, cadaveric brain specimens, healthy volunteers, and patients with multiple sclerosis (MS). A total of 20 healthy volunteers (mean age, 40 years ± 13 [standard deviation], 10 women) and 20 patients with MS (mean age, 58 years ± 8; 15 women) who underwent MRI between November 2017 and February 2019 were prospectively included. Analysis of variance was performed to evaluate the signal difference between MS lesions and normal-appearing white matter in patients with MS. Results High signal intensity and corresponding T2* and T1 of the extracted myelin vesicles provided evidence for direct imaging of ultrashort-T2 myelin protons using the UTE sequence. Gadobenate dimeglumine phantoms with a wide range of T1 values were selectively suppressed with DESIRE UTE. In the ex vivo brain study of MS lesions, signal loss was observed in MS lesions and was conformed with histologic analysis. In the human study, there was a significant reduction in normalized signal intensity in MS lesions compared with that in normal-appearing white matter (0.19 ± 0.10 vs 0.76 ± 0.11, respectively; P < .001). Conclusion The double-echo sliding inversion recovery ultrashort echo time sequence can generate whole-brain myelin images specifically with a clinical 3-T scanner. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Port in this issue.

Purpose: Management of eosinophilic esophagitis (EoE) varies from center to center. In this study, we evaluated the effectiveness of a dairy-free diet (DFD) and the 6-Food Elimination Diet (SFED) as initial therapies for the treatment of EoE in our practice., Methods: This was a retrospective study of children who had been treated for EoE at Connecticut Children's Medical Center, Hartford, CT, USA. Pre- and post-treatment endoscopy findings and histology results of patients treated with DFD or SFED were examined., Results: One hundred fifty-two patients (age 9.2±5.2 years, 76.3% male, 69.7% caucasian) met the inclusion criteria for initial treatment with DFD (n=102) or SFED (n=50). Response for DFD was 56.9% and for SFED was 52.0%. Response based on treatment duration (<10, 10-12, and >12 weeks) were 81.8%, 50.0%, and 55.1% for DFD, and 68.8%, 50.0%, and 40.0% for SFED. Response based on age (<6, 6-12, and >12 years) were 59.3%, 42.9%, and 67.5% for DFD, and 36.4%, 58.8%, and 72.7% for SFED. In patients treated with DFD, concomitant proton pump inhibitor (PPI) administration resulted in improved outcomes ( p =0.0177). Bivariate regression analysis showed that PPI with diet is the only predictor of response ( p =0.0491), however, there were no significant predictors on multiple regression analysis., Conclusion: DFD and SFED are effective first line therapies for EoE. DFD should be tried first before extensive elimination diets. Concomitant therapy with PPI's may be helpful., Competing Interests: Conflicts of Interest: The authors have no financial conflicts of interest., (Copyright © 2020 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition.)

To be time and resource efficient in neonatal research and to answer clinically relevant questions with validity and generalizability, large numbers of infants from multiple hospitals need to be included. Multijurisdictional research in Canada is currently fraught with research ethics review process hurdles that lead to delays, administrative costs, and possibly termination of projects. We describe our experience applying for ethics review to 13 sites in 7 provinces for a project comparing two standard of care therapies for preterm born infants with respiratory distress syndrome. We welcome the current opportunity created by the Institute of Human Development Child and Youth Health and the Institute for Genetics, to collaboratively identify practical solutions that would benefit Canadian researchers, Research Ethics Boards, and children and families., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The primary aim of the present article was to review the effect and the clinical significance of abutment dis- and reconnection on the peri-implant marginal bone levels., Materials and Methods: English articles published from 2009 to April 2019 were identified on the MEDLINE, Cochrane Library, and PubMed databases, according to the PRISMA guidelines. Comparative in vivo studies on humans were included., Results: A total of 4 studies with different levels of bias were included in this review. A significant heterogeneity of the reported data was observed, which limited the comparison of the findings. The only parameter that was homogenous throughout all 4 studies was the marginal bone level measurement., Conclusion: Within the limitations of the present review, it can be suggested that minimizing the number of abutment dis- and reconnections would be beneficial to ensure minimal disruption to the peri-implant tissue and marginal bone level. However, the clinical significance of the marginal bone level changes is still inconclusive.

Management practices in early-stage (I/II) follicular lymphoma (FL) are variable and include radiation (RT), systemic therapy, or combined modality therapy (CMT). There is a paucity of data regarding maintenance rituximab in this cohort. We conducted an international retrospective study of patients with newly diagnosed early-stage FL staged with positron emission tomography (PET)-computed tomography and bone marrow biopsy. Three hundred sixty-five patients (stage I, n = 221), median age 63 years, treated from 2005-2017 were included, with a median follow-up of 45 months. Management included watchful waiting (WW; n = 85) and active treatment (n = 280). The latter consisted of RT alone (n = 171) or systemic therapy (immunochemotherapy [n = 63] or CMT [n = 46]). Forty-nine systemically treated patients received maintenance rituximab; 72.7% of stage I patients received RT alone, compared to 42.6% with stage II ( P < .001). Active therapies yielded comparable overall response rates ( P = .87). RT alone and systemic therapy without maintenance rituximab yielded similar progression-free survival (PFS) (hazard ratio [HR], 1.32; 95% confidence interval [CI], 0.77-2.34; P = .96). Maintenance rituximab improved PFS (HR, 0.24; 95% CI, 0.095-0.64; P = .017). The incidence of transformation was lower with systemic therapy compared to RT or WW (HR, 0.20; 95% CI, 0.070-0.61; P = .034). Overall survival was similar among all practices, including WW ( P = .40). In the largest comparative assessment of management practices in the modern era, variable practices each resulted in similar excellent outcomes. Randomized studies are required to determine the optimal treatment in early-stage FL., (© 2019 by The American Society of Hematology.)

Introduction: The gastrointestinal tract is a potential source of inflammation in dialysis patients. In vitro studies suggest breakdown of the gut barrier in uraemia leading to increased intestinal permeability and it is hypothesised that haemodialysis exacerbates this problem due to mesenteric ischaemia induced by blood volume changes during treatment., Method: The effect of haemodialysis on intestinal permeability was studied in ten haemodialysis patients and compared with five controls. Intestinal permeability was assessed by measuring the differential absorption of four orally administered sugar probes which provides an index of small and whole bowel permeability. A multi-sugar solution (containing lactulose, rhamnose, sucralose and erythritol) was orally administered after an overnight fast. Plasma levels of all sugar probes were measured hourly for 10 h post-administration. In haemodialysis patients, the procedure was carried out twice - once on a non-dialysis day and once immediately after haemodialysis., Results: Area under curve (AUC) for lactulose:rhamnose (L:R) ratio and sucralose:erythritol (S:E) ratio was similar post-dialysis and on non-dialysis days. AUC for L:R was higher in haemodialysis patients compared with controls (0.071 vs. 0.034, P =0.001), AUC for S:E ratio was not significantly different. Levels of lactulose, sucralose and erythritol were elevated and retained longer in haemodialysis patients compared with controls due to dependence of sugars on kidney function for clearance., Conclusion: We found no significant acute changes in intestinal permeability in relation to the haemodialysis procedure. Valid comparison of intestinal permeability between controls and haemodialysis patients was not possible due to the strong influence of kidney function on sugar levels., (© 2019 The Author(s).)

An environmentally benign and highly versatile catalytic protocol has been successfully applied in the intermolecular bromoesterification between various olefins and carboxylic acids. The use of a highly lipophilic indole catalyst and 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) as the bromine source allows the reaction to proceed in heptane via a solid-liquid phase transfer mechanism, affording the corresponding bromoester products in good-to-excellent yields.

Pelvic floor disorders negatively impact millions of women worldwide. Although there is a strong epidemiological association with childbirth, the mechanisms leading to the dysfunction of the integral constituents of the female pelvic floor, including pelvic floor skeletal muscles, are not well understood. This is in part due to the constraints associated with directly probing these muscles, which are located deep in the pelvis. Thus, experimental models and non-invasive techniques are essential for advancing knowledge of various phenotypes of pelvic floor muscle injury and pathogenesis of muscle dysfunction, as well as developing minimally invasive approaches for the delivery of novel therapeutics. The most widely used animal model for pelvic floor disorders is the rat. However, the radiological anatomy of rat pelvic floor muscles has not been described. To remedy this gap, the current study provides the first detailed description of the female rat pelvic floor muscles' radiological appearance on MR and ultrasound images, validated by correlation with gross anatomy and histology. We also demonstrate that ultrasound guidance can be used to target rat pelvic floor muscles for possible interventional therapies., (© 2019 Anatomical Society.)

Background:: Dyspnea is distressing in palliative patients with end-stage heart failure and many are hospitalized to optimize this symptom. We hoped to conduct a pilot study to determine whether the administration of intranasal fentanyl would decrease activity-induced dyspnea in this patient population., Methods:: Patients performed two 6-minute walk tests with and without the administration of 50 μg of intranasal fentanyl. Vital signs were recorded before and after each walk, as were participant reported dyspnea and adverse events scores., Results:: Twenty-four patients were screened, 13 were deemed eligible, and 6 completed the study. Dyspnea scores changed from a mean of 6.00 immediately after the walk without fentanyl to a mean of 3.83 after the walk with fentanyl ( P = .048). Mean respiratory rate decreased from 21.0 to 18.7 ( P = .034) breaths per minute and was considered a favorable outcome by the participants. Distance walked did not significantly increase with the fentanyl pretreatment (136.0-144.2 m; P = .283), although the participants reported feeling better while walking a similar distance., Conclusions:: In this pilot study, the preadministration of intranasal fentanyl prior to activity in palliative, end-stage hospitalized heart failure patients, safely reduced tachypnea, and the feeling of shortness of breath. This approach may help palliate advanced heart failure patients by alleviating symptoms brought on by exertional activities.

The electrochemical reduction of CO and CO 2 over Cu produces a variety of multicarbon products. Interestingly, recent isotope experiments have suggested that the oxygen atoms contained in the multicarbon alcohols produced over Cu are derived from solvent water. This observation has brought into question many of the proposed reaction mechanisms by which these multicarbon alcohols are produced over Cu. However, these surprising experimental observations are likely the result of isotopic scrambling between transiently produced carbonyl-containing intermediate reaction products, such as acetaldehyde, with solvent water and not another mechanism. The existence of such carbonyl-containing intermediate reaction products is supported by both experimental and theoretical studies. Furthermore, theoretical calculations support the notion that the reversible hydration of these carbonyl-containing species is facile in the vicinity of the Cu surface.

Background: Acquired hypogammaglobulinaemia secondary to haematological malignancies is associated with increased infection risk. Immunoglobulin (Ig) replacement reduces major infections but not mortality, and is costly. No prospective randomised trials have compared Ig replacement with prophylactic antibiotics., Aims: To identify variation in current practice regarding management of secondary hypogammaglobulinaemia in Australia and New Zealand, to identify barriers to best practice, and to inform the development of a clinical trial assessing antibiotic prophylaxis in secondary hypogammaglobulinaemia., Methods: We conducted an online survey of current clinical practice regarding management of secondary hypogammaglobulinaemia among haematologists in Australia and New Zealand., Results: Seventy-two haematologists responded; 89% of whom reported commencing Ig replacement for secondary hypogammaglobulinaemia in the setting of recurrent or severe infection. Most monitored trough immunoglobulin G levels, most often 3 monthly. Criteria for stopping Ig replacement varied. Most respondents recommended influenza and pneumococcal vaccination, while only 21% reported using antibiotic prophylaxis. Few respondents (3%) reported prescribing prophylactic antibiotics before commencing Ig replacement. Most reported an interest in recruiting patients to a clinical trial comparing Ig replacement with prophylactic antibiotics., Conclusion: In comparison to limited international data, this survey finds variation in practice, which may be due to differences in local policies governing access to Ig. These findings highlight the need for research into the indications for Ig commencement and cessation, and will inform design of prospective trials of infection prevention in secondary hypogammaglobulinaemia., (© 2018 Royal Australasian College of Physicians.)