bluuebunny/crossref_metadata_2025 huggingface dataset:
Are meal kits health promoting? Nutritional analysis of meals from an Australian meal kit service
Authors: Moores Carly J , Bell Lucinda K , Buckingham Michael J , Dickinson Kacie M
Published: August 2020

Meal kits are popular for consumers seeking greater convenience in preparing meals at home. The market share for meal kit subscription services (MKSSs) is growing in developed nations including Australia, however, literature about their health promoting qualities, e.g. nutritional composition, is scarce. This study aimed to assess the characteristics and nutritional composition of meals offered from an MKSS over 12 months. Nutritional data were extracted from recipes available to order from HelloFresh in Australia from 1 July 2017 to 30 June 2018. In total, 346 (251 unique) recipes were retrieved. Per serve (median size 580 g), meals contained a median of 2840 kJ (678 kcal) of energy, 58 g carbohydrate (14 g sugar), 44 g protein, 28 g total fat (8 g saturated fat) and 839 mg sodium. Median energy from macronutrients was total fat (38%), carbohydrates (34%), protein (25%) and saturated fat (11%). This paper is the first to describe characteristics of recipes available from an MKSS over a 12-month period of time. With their growing popularity, meal kit delivery services have the capacity to influence consumer food behaviours, diets and subsequently population health. MKSSs may function to promote health though education, training, and enabling home cooking behaviours, and may be a powerful commitment device for home cooking behaviour change. However, it is important for health professionals, including dietitians and nutritionists, to understand the nutritional risks, benefits and suitability of this contemporary mealtime option before recommending them to clients and members of the public as part of health promotion.

Lay summary

Meal kit delivery services are growing in popularity in developed countries, complementing busy lifestyles with pre-measured ingredients and recipe instructions delivered to the home. These meal kits have the ability to influence consumer diets and population health, and may support health promoting diet behaviours, e.g. eating vegetables, and enable home cooking. In this study, we reviewed a years’ worth of recipes from a popular meal kit service. We report that a typical recipe contained approximately nine different ingredients, comprising three vegetables and required three ingredients from the home pantry. Meals took ∼35 min to prepare and were found to be relatively high in energy from fat and protein, and relatively low in energy from carbohydrates. The level of sodium varied widely and some meals exceeded the Australian Suggested Dietary Target for sodium (<2000 mg). Meal kit recipes were found to have health promoting qualities, frequently including vegetable ingredients, however, improvements to recipes would make these meal kits more health promoting. Current diet intakes and the nutritional composition of meal kits recipes should be reviewed before being recommended by health professionals.
The implementation process of the Confident Birth method in Swedish antenatal education: opportunities, obstacles and recommendations
Authors: Jansson Sofia , Farahshoor Sepideh , Linden Karolina , Bogren Malin
Published: August 2020

Antenatal clinics in western Sweden have recently invested in a birth method called Confident Birth. In this study, we investigate midwives’ and first line managers’ perceptions regarding the method, and identify opportunities and obstacles in its implementation. Semi-structured individual interviews were conducted with ten midwives and five first line managers working in 19 antenatal clinics in western Sweden. The Consolidated Framework for Implementation Research was used in a directed content analysis approach. Intervention Characteristics—such as perceptions about the Confident Birth method—were found to have equipped the midwives with coping strategies that were useful for expecting parents during birth. Outer Setting—the method was implemented to harmonize the antenatal education, and provided a mean for a birth companionship of choice. Inner setting—included time-consuming preparations and insufficient information at all levels, which affected the implementation. Characteristics of individuals—, such as knowledge and believes in the method, where trust in the method was seen as an opportunity, while long experience of teaching other birth preparatory methods, affected how the Confident Birth method was perceived. Process—such as no strategy for ensuring that the core of the method remained intact or plans for guiding its implementation were major obstacles to successful implementation. The findings speak to the importance of adequate planning, time, information and communication throughout the process to have a successful implementation. Based on lessons learned from this study, we have developed recommendations for successful implementation of interventions, such as the Confident Birth, in antenatal care settings.
Results of a mixed methods evaluation of the Make Healthy Normal campaign
Authors: Kite James , Thomas Margaret , Grunseit Anne , Li Vincy , Bellew William , Bauman Adrian
Published: August 2020

The Make Healthy Normal obesity prevention mass media campaign was implemented in New South Wales, Australia from 2015 to 2018. This study evaluated Phase 2 (2017–18) of that campaign, using three cross-sectional online surveys with men aged 18–54 years (n = 4352) and six focus groups with men aged 35–54 years and parents with children aged 5–12 years (n = 38), reflecting the campaign’s target audiences. We used linear and logistic regressions to examine changes over time in key outcomes, consistent with the campaign’s theorized hierarchy of effects. Focus group data were analysed thematically and integrated with survey results at the interpretation stage. Survey results showed reasonable prompted recognition, although unprompted recall remained low, and there were no consistent, positive shifts in other outcomes, including behaviour. Focus group results suggested that this was because the campaign’s messages, while considered clear and relevant, did not address the constraints participants experienced that made change difficult. Hence, the campaign by itself was unlikely to lead to behaviour change. We need to reconsider the role of campaigns in addressing multi-determined and complex problems. Evaluations should reconsider metrics of success, as they may not immediately result in behaviour change, especially in the absence of complementary policy and environmental strategies.
‘I will welcome this one 101%, I will so embrace it’: a qualitative exploration of the feasibility and acceptability of HIV self-testing among men who have sex with men (MSM) in Lagos, Nigeria
Authors: Dirisu Osasuyi , Sekoni Adekemi , Vu Lung , Adebajo Sylvia , Njab Jean , Shoyemi Elizabeth , Ogunsola Sade , Tun Waimar
Published: August 2020

Men who have sex with men (MSM) are disproportionately affected by HIV in Nigeria. A key strategy in reducing transmission is to increase HIV testing uptake and linkage to treatment for those who test positive. HIV self-testing (HIVST) is an innovative strategy with the potential to increase uptake of HIV testing among key populations at higher risk for HIV. We conducted 23 in-depth-interviews with MSM and two focus group discussions with key opinion leaders to explore perceptions about the feasibility and acceptability of oral HIVST among MSM in Lagos, Nigeria. HIVST was highly acceptable because it was considered convenient to use, painless, private and addressed concerns about stigma. Concerns cited by participants included comprehensibility of instructions to perform and interpret results correctly, as well as lack of support mechanisms to facilitate post-test follow-up and linkage to care. Provision of adequate pre-test information was considered vital as part of the kit distribution process to ensure seamless use of HIVST kits. One-on-one peer-to-peer distribution strategies and retail outlets that facilitate anonymous pick-up are potential distribution channels identified in this study. Overall, our findings suggest that an HIVST program that incorporates these considerations would improve access to HIV testing among MSM in Nigeria.
Peri-implantation intercourse does not lower fecundability
Authors: Stanford Joseph B , Hansen Jared L , Willis Sydney K , Hu Nan , Thomas Alun
Published: August 2020

STUDY QUESTION

Does sexual intercourse in the implantation time window (5–9 days after ovulation) reduce fecundability?

SUMMARY ANSWER

After adjustment for intercourse in the fecund window and clustering by couple, there was no association between intercourse in the implantation time window and fecundity.

WHAT IS KNOWN ALREADY

Previous research has suggested an association between intercourse in the peri-implantation time window (5–9 days after estimated ovulation) and reduced fecundability.

STUDY DESIGN, SIZE, DURATION

We used data from the FERTILI study, a prospective observational study conducted in five European countries, with data collected from 1992 to 1996.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Women who were experienced in fertility awareness tracking kept a daily diary of cervical mucus observations, basal body temperature measurements, coitus and clinically identified pregnancy. We estimated the day of ovulation as cycle length minus 13 days. From 661 women, 2606 cycles had intercourse during the fecund window (from 5 days before to 3 days after the estimated day of ovulation), resulting in 418 pregnancies (conception cycles). An established Bayesian fecundability model was used to estimate the fecundability ratio (FR) of peri-implantation intercourse on fecundability, while adjusting for each partner’s age, prior pregnancy, the couple’s probability of conception and intercourse pattern(s). We conducted sensitivity analyses estimating ovulation as cycle length minus 12 days, or alternatively, as the peak day of estrogenic cervical mucus.

MAIN RESULTS AND THE ROLE OF CHANCE

There was no effect of peri-implantation intercourse on fecundability: adjusted FR for three or more acts of peri-implantation intercourse versus none: 1.00, 95% credible interval: 0.76–1.13. Results were essentially the same with sensitivity analyses. There was an inverse relationship between frequency of intercourse in the fecund window and intercourse in the peri-implantation window.

LIMITATIONS, REASONS FOR CAUTION

Women with known subfertility were excluded from this study. Many couples in the study were avoiding pregnancy during much of the study, so 61% of otherwise eligible cycles in the database were not at meaningful risk of pregnancy and did not contribute to the analysis. Some couples may not have recorded all intercourse.

WIDER IMPLICATIONS OF THE FINDINGS

We believe the current balance of evidence does not support a recommendation for avoiding intercourse in the peri-implantation period among couples trying to conceive.

STUDY FUNDING/COMPETING INTEREST(S)

No external funding. The authors have no potential competing interests.

TRIAL REGISTRATION NUMBER

N/A.
The effect of Day 3 cell number on pregnancy outcomes in vitrified-thawed single blastocyst transfer cycles
Authors: Wu Jiayi , Zhang Jie , Kuang Yanping , Chen Qiuju , Wang Yun
Published: August 2020

STUDY QUESTION

Does cell number on Day 3 have an impact on pregnancy outcomes in vitrified-thawed single blastocyst transfer cycles?

SUMMARY ANSWER

A low Day 3 cell number (≤5 cells) was independently associated with decreased live birth rate (LBR) during single blastocyst transfer cycles in young women.

WHAT IS KNOWN ALREADY

Day 3 cell number is an effective predictor of IVF success rates when transferring cleavage stage embryos. However, the association between Day 3 blastomere number and pregnancy outcomes after blastocyst transfer is still unknown.

STUDY DESIGN, SIZE, DURATION

A retrospective cohort study of 3543 patients who underwent frozen-thawed single blastocyst transfers from January 2013 to June 2018 at a tertiary-care academic medical center.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Patients were grouped into six groups according to the Day 3 cell number: ≤4 cells, 5 cells, 6 cells, 7 cells, 8 cells and >8 cells. The primary outcome measure was LBR. A logistic regression analysis was performed to explore the independent association between Day 3 blastomere number and LBR after adjustment for some potential confounders.

MAIN RESULTS AND THE ROLE OF CHANCE

In women <35 years old, the LBR varied significantly according to Day 3 cell number, with the rate of 31.2%, 34.4%, 41.9%, 45.1%, 48.1% and 48.2% for the ≤4-cell, 5-cell, 6-cell, 7-cell, 8-cell and >8-cell groups, respectively (P < 0.001). This significant difference was also observed in the high- and low-quality blastocyst subgroups of young women. However, for women ≥35 years old, the rate of live birth was similar between groups. Furthermore, after accounting for confounding factors, the LBR was significantly decreased in the ≤4-cell (adjusted odds ratio (aOR): 0.62, 95% CI: 0.48–0.80, P < 0.001) and 5-cell (aOR: 0.73, 95% CI: 0.57–0.92, P = 0.009) groups as compared to the 8-cell group. Likewise, the blastocysts arising from ≤4-cell (aOR: 0.73, 95% CI: 0.57–0.93, P = 0.010) or 5-cell (aOR: 0.77, 95% CI: 0.61–0.97, P = 0.024) embryos were associated with lower clinical pregnancy rate than those from 8-cell embryos. No significant differences were observed in biochemical pregnancy rate and miscarriage rate.

LIMITATIONS, REASONS FOR CAUTION

A limitation of the current study was its retrospective design. Future prospective studies are needed to confirm our findings.

WIDER IMPLICATIONS OF THE FINDINGS

Our observations suggested that a low Day 3 cell number was related to decreased LBR after blastocyst transfer in young women, which provided vital information for clinicians in selecting blastocyst during IVF treatment.

STUDY FUNDING/COMPETING INTEREST(S)

This study was supported by the National Natural Science Foundation of China (NSFC) (31770989 to Y.W.; 81671520 to Q.C.) and the Shanghai Ninth People’s Hospital Foundation of China (JYLJ030 to Y.W.). The authors have no conflicts of interest to declare.

TRIAL REGISTRATION NUMBER

N/A.
Functional Morphology of Gliding Flight I: Modeling Reveals Distinct Performance Landscapes Based on Soaring Strategies
Authors: Waldrop Lindsay D , He Yanyan , Hedrick Tyson L , Rader Jonathan A
Published: August 2020

Synopsis

The physics of flight influences the morphology of bird wings through natural selection on flight performance. The connection between wing morphology and performance is unclear due to the complex relationships between various parameters of flight. In order to better understand this connection, we present a holistic analysis of gliding flight that preserves complex relationships between parameters. We use a computational model of gliding flight, along with analysis by uncertainty quantification, to (1) create performance landscapes of gliding based on output metrics (maximum lift-to-drag ratio, minimum gliding angle, minimum sinking speed, and lift coefficient at minimum sinking speed) and (2) predict what parameters of flight (chordwise camber, wing aspect ratio [AR], and Reynolds number) would differ between gliding and nongliding species of birds. We also examine performance based on the soaring strategy for possible differences in morphology within gliding birds. Gliding birds likely have greater ARs than non-gliding birds, due to the high sensitivity of AR on most metrics of gliding performance. Furthermore, gliding birds can use two distinct soaring strategies based on performance landscapes. First, maximizing distance traveled (maximizing lift-to-drag ratio and minimizing gliding angle) should result in wings with high ARs and middling-to-low wing chordwise camber. Second, maximizing lift extracted from updrafts should result in wings with middling ARs and high wing chordwise camber. Following studies can test these hypotheses using morphological measurements.
Rare indications for a lung transplant. A European Society of Thoracic Surgeons survey
Authors: Nosotti Mario , D’Ovidio Frank , Leiva-Juarez Miguel , Keshavjee Shaf , Rackauskas Mindaugas , Van Raemdonck Dirk , Ceulemans Laurens J , Krueger Thorsten , Koutsokera Angela , Schiavon Marco , Rea Federico , Iskender Ilker , Moreno Paula , Alvarez Antonio , Luzzi Luca , Paladini Piero , Rosso Lorenzo , Bertani Alessandro , Venuta Federico , Pecoraro Ylenia , Al-Kattan Khaled , Kubisa Bartosz , Inci Ilhan
Published: August 2020

OBJECTIVES

The European Society of Thoracic Surgeons Lung Transplantation Working Group promoted a survey to evaluate overall survival in a large cohort of patients receiving lung transplants for rare pulmonary diseases.

METHODS

We conducted a retrospective multicentre study. The primary end point was overall survival; secondary end points were survival of patients with the most common diagnoses in the context of rare pulmonary diseases and chronic lung allograft dysfunction (CLAD)-free survival. Finally, we analysed risk factors for overall survival and CLAD-free survival.

RESULTS

Clinical records of 674 patients were extracted and collected from 13 lung transplant centres; diagnoses included 46 rare pulmonary diseases. Patients were followed for a median of 3.1 years. The median survival after a lung transplant was 8.5 years. The median CLAD-free survival was 8 years. The multivariable analysis for mortality identified CLAD as a strong negative predictor [hazard ratio (HR) 6.73)], whereas induction therapy was a protective factor (HR 0.68). The multivariable analysis for CLAD occurrence identified induction therapy as a protective factor (HR 0.51). When we stratified patients by CLAD occurrence in a Kaplan–Meier plot, the survival curves diverged significantly (log-rank test: P < 0.001). Patients with rare diseases who received transplants had chronic rejection rates similar to those of the general population who received transplants.

CONCLUSIONS

We observed that overall survival and CLAD-free survival were excellent. We support the practice of allocating lungs to patients with rare pulmonary diseases because a lung transplant is both effective and ethically acceptable.
Human corpse model for video-assisted thoracoscopic lobectomy simulation and training
Authors: Dell’Amore Andrea , Boscolo-Berto Rafael , Schiavon Marco , Pangoni Alessandro , Porzionato Andrea , Macchi Veronica , De Caro Raffaele , Rea Federico
Published: August 2020

OBJECTIVES

Minimally invasive surgery simulation is an integral part of surgical education and skills acquisition. Our goal was to present a new video-assisted thoracic surgery simulation model based on the human corpse as an alternative to animal models.

METHODS

Selective cannulation of the cadaver heart was used to fill the pulmonary vessels with a gel to improve the visibility and tactile feedback of the vessels and to simulate any bleeding complications. During surgical simulation, the tutor fills out a questionnaire designed to evaluate the duration of the procedure, the correct completion of the surgical steps and the occurrence of complications. At the end of the simulation session, in order to compare the simulation to clinical practice, all the participants were asked to answer 5 questions using a scale from 1 to 10.

RESULTS

We have performed 2 hands-on sessions using 2 human corpses for each session. Each surgeon performed 1 lobectomy using video-assisted thoracoscopic surgery (VATS) first as the operator and at least 1 lobectomy as an assistant. The median operative time was 83 min in favour of surgeons who had previously performed more than 30 video-assisted lobectomies (P = 0.03). All the surgeons were able to complete all the steps of the procedure; surgeons who had performed fewer than 10 lobectomies required more support by the tutors than the other surgeons. The median total score was 40.5 (interquartile range 39–44.8).

CONCLUSIONS

We believe that this model includes most of the features necessary to validate a surgical simulator and allows realistic training for performing a VATS lobectomy. This model could be an effective alternative to anaesthetized animals for VATS lobectomy training and simulation.
Redo sternotomy versus left ventricular assist device explant as risk factors for early mortality following heart transplantation
Authors: Ribeiro Roberto Vanin Pinto , Alvarez Juglans Souto , Fukunaga Naoto , Yu Frank , Adamson Mitchell Brady , Foroutan Farid , Cusimano Robert James , Yau Terrence , Ross Heather , Alba Ana Carolina , Billia Filio , Badiwala Mitesh Vallabh , Rao Vivek
Published: August 2020

OBJECTIVES

There is an increasing proportion of patients with a previous sternotomy (PS) or durable left ventricular assist device (LVAD) undergoing heart transplantation (HT). We hypothesized that patients with LVAD support at the time of HT have a lower risk than patients with PS and may have a comparable risk to patients with a virgin chest (VC).

METHODS

This is a single-centre retrospective cohort study of all adults who underwent primary single-organ HT between 2002 and 2017. Multivariable Cox regression analyses were performed to compare 30-day and 1-year mortality between transplanted patients with a VC (VC-HT), a PS (PS-HT) or an LVAD explant (LVAD-HT).

RESULTS

Three hundred seventy-nine patients were analysed (VC-HT: 196, PS-HT: 94, LVAD-HT: 89). A larger proportion of patients in the LVAD-HT group were males (83%), had blood group O (52%), non-ischaemic aetiology (70%) and sensitization (67%). The PS-HT group had a higher frequency of patients with congenital heart disease (30%) and PSs compared to LVAD-HT patients (P < 0.001). PS-HT and LVAD-HT patients required a longer bypass time (P < 0.001) and showed a greater estimated blood loss (P < 0.001). Postoperatively, LVAD-HT required haemodialysis more frequently than the VC-HT group (P = 0.031). Multivariable analyses found that PS-HT patients had increased 30-day mortality compared to VC-HT [hazard ratio (HR) 2.63, 95% confidence interval (CI) 1.15–6.01; P = 0.022] while LVAD-HT did not (HR 2.17, 95% CI 0.96–4.93; P = 0.064). At 1-year, neither PS-HT nor LVAD-HT groups were significantly associated with increased mortality compared to VC-HT.

CONCLUSIONS

Transplants in recipients with PS-HT demonstrated increased early mortality compared to VC-HT patients. Although LVAD explant is often technically challenging, this population demonstrated similar mortality compared to those VC-HT patients. The chronic and perioperative support provided by the LVAD may play a favourable role in early patient outcomes compared to other redo sternotomy patients.
When Law Forgets: Coherence and Memory in the Determination of Stateless Palestinian Refugee Claims in Canada
Authors: Blum Joshua
Published: August 2020

This article highlights the incoherence in Canada’s treatment of many Palestinian refugee claims, and argues that this state of affairs is best understood as a failure of legal memory. The drafters of the Refugee Convention recognized both Palestinian refugees’ collective entitlement to protection, and the distinct protection needs of stateless persons. Canadian refugee law, however, contains no trace of this history. As a result, refugee determination in Canada does not account for the persecution that caused and maintains Palestinian statelessness, and holds an often-misplaced focus on where a stateless person ‘habitually resided’ at the expense of where they are actually at risk. This article charts the path to the present legal regime for stateless Palestinian refugee claimants in Canada, and identifies three problematic trends in the application of the Convention refugee definition to Palestinian claims. Alternative interpretations of the law are then offered to restore recognition of the collective nature of the persecution of Palestinian refugees, and the distinct human rights problem of statelessness.
A finite element error analysis for axisymmetric mean curvature flow
Authors: Barrett John W , Deckelnick Klaus , Nürnberg Robert
Published: August 2020

We consider the numerical approximation of axisymmetric mean curvature flow with the help of linear finite elements. In the case of a closed genus-1 surface we derive optimal error bounds with respect to the $L^2$- and $H^1$-norms for a fully discrete approximation. We perform convergence experiments to confirm the theoretical results and also present numerical simulations for some genus-0 and genus-1 surfaces, including for the Angenent torus.
The Exceptional Locus in the Bertini Irreducibility Theorem for a Morphism
Authors: Poonen Bjorn , Slavov Kaloyan
Published: August 2020

We introduce a novel approach to Bertini irreducibility theorems over an arbitrary field, based on random hyperplane slicing over a finite field. Extending a result of Benoist, we prove that for a morphism $\phi \colon X \to{\mathbb{P}}^n$ such that $X$ is geometrically irreducible and the nonempty fibers of $\phi $ all have the same dimension, the locus of hyperplanes $H$ such that $\phi ^{-1} H$ is not geometrically irreducible has dimension at most ${\operatorname{codim}}\ \phi (X)+1$. We give an application to monodromy groups above hyperplane sections.
Central Limit Theorem for Mesoscopic Eigenvalue Statistics of the Free Sum of Matrices
Authors: Bao Zhigang , Schnelli Kevin , Xu Yuanyuan
Published: August 2020

We consider random matrices of the form $H_N=A_N+U_N B_N U^*_N$, where $A_N$ and $B_N$ are two $N$ by $N$ deterministic Hermitian matrices and $U_N$ is a Haar distributed random unitary matrix. We establish a universal central limit theorem for the linear eigenvalue statistics of $H_N$ on all mesoscopic scales inside the regular bulk of the spectrum. The proof is based on studying the characteristic function of the linear eigenvalue statistics and consists of two main steps: (1) generating Ward identities using the left-translation invariance of the Haar measure, along with a local law for the resolvent of $H_N$ and analytic subordination properties of the free additive convolution, allows us to derive an explicit formula for the derivative of the characteristic function; (2) a local law for two-point product functions of resolvents is derived using a partial randomness decomposition of the Haar measure. We also prove the corresponding results for orthogonal conjugations.
PBW Property for Associative Universal Enveloping Algebras Over an Operad
Authors: Khoroshkin Anton
Published: August 2020

Given a symmetric operad $\mathcal{P}$ and a $\mathcal{P}$-algebra $V$, the associative universal enveloping algebra ${\textsf{U}_{\mathcal{P}}}$ is an associative algebra whose category of modules is isomorphic to the abelian category of $V$-modules. We study the notion of PBW property for universal enveloping algebras over an operad. In case $\mathcal{P}$ is Koszul a criterion for the PBW property is found. A necessary condition on the Hilbert series for $\mathcal{P}$ is discovered. Moreover, given any symmetric operad $\mathcal{P}$, together with a Gröbner basis $G$, a condition is given in terms of the structure of the underlying trees associated with leading monomials of $G$, sufficient for the PBW property to hold. Examples are provided.
Evaluation of Serological Tests for SARS-CoV-2: Implications for Serology Testing in a Low-Prevalence Setting
Authors: Bond Katherine , Nicholson Suellen , Lim Seok Ming , Karapanagiotidis Theo , Williams Eloise , Johnson Douglas , Hoang Tuyet , Sia Cheryll , Purcell Damian , Mordant Francesca , Lewin Sharon R , Catton Mike , Subbarao Kanta , Howden Benjamin P , Williamson Deborah A
Published: August 2020

Background

Robust serological assays are essential for long-term control of the COVID-19 pandemic. Many recently released point-of-care (PoCT) serological assays have been distributed with little premarket validation.

Methods

Performance characteristics for 5 PoCT lateral flow devices approved for use in Australia were compared to a commercial enzyme immunoassay (ELISA) and a recently described novel surrogate virus neutralization test (sVNT).

Results

Sensitivities for PoCT ranged from 51.8% (95% confidence interval [CI], 43.1%–60.4%) to 67.9% (95% CI, 59.4%–75.6%), and specificities from 95.6% (95% CI, 89.2%–98.8%) to 100.0% (95% CI, 96.1%–100.0%). ELISA sensitivity for IgA or IgG detection was 67.9% (95% CI, 59.4%–75.6%), increasing to 93.8% (95% CI, 85.0%–98.3%) for samples >14 days post symptom onset. sVNT sensitivity was 60.9% (95% CI, 53.2%–68.4%), rising to 91.2% (95% CI, 81.8%–96.7%) for samples >14 days post symptom onset, with specificity 94.4% (95% CI, 89.2%–97.5%).

Conclusions

Performance characteristics for COVID-19 serological assays were generally lower than those reported by manufacturers. Timing of specimen collection relative to onset of illness or infection is crucial in reporting of performance characteristics for COVID-19 serological assays. The optimal algorithm for implementing serological testing for COVID-19 remains to be determined, particularly in low-prevalence settings.
SARS-CoV-2–Specific Antibody Detection for Seroepidemiology: A Multiplex Analysis Approach Accounting for Accurate Seroprevalence
Authors: den Hartog Gerco , Schepp Rutger M , Kuijer Marjan , GeurtsvanKessel Corine , van Beek Josine , Rots Nynke , Koopmans Marion P G , van der Klis Fiona R M , van Binnendijk Robert S
Published: August 2020

Background

The COVID-19 pandemic necessitates better understanding of the kinetics of antibody production induced by infection with SARS-CoV-2. We aimed to develop a high-throughput multiplex assay to detect antibodies to SARS-CoV-2 to assess immunity to the virus in the general population.

Methods

Spike protein subunits S1 and receptor binding domain, and nucleoprotein were coupled to microspheres. Sera collected before emergence of SARS-CoV-2 (n = 224) and of non-SARS-CoV-2 influenza-like illness (n = 184), and laboratory-confirmed cases of SARS-CoV-2 infection (n = 115) with various severities of COVID-19 were tested for SARS-CoV-2–specific IgG concentrations.

Results

Our assay discriminated SARS-CoV-2–induced antibodies and those induced by other viruses. The assay specificity was 95.1%–99.0% with sensitivity 83.6%–95.7%. By merging the test results for all 3 antigens a specificity of 100% was achieved with a sensitivity of at least 90%. Hospitalized COVID-19 patients developed higher IgG concentrations and the rate of IgG production increased faster compared to nonhospitalized cases.

Conclusions

The bead-based serological assay for quantitation of SARS-CoV-2–specific antibodies proved to be robust and can be conducted in many laboratories. We demonstrated that testing of antibodies against multiple antigens increases sensitivity and specificity compared to single-antigen–specific IgG determination.
Fc receptor-like 4 and 5 define human atypical memory B cells
Authors: Li Huifang , Dement-Brown Jessica , Liao Pei-Jyun , Mazo Ilya , Mills Frederick , Kraus Zachary , Fitzsimmons Sean , Tolnay Mate
Published: August 2020

Atypical memory B cells accumulate in chronic infections and autoimmune conditions, and commonly express FCRL4 and FCRL5, respective IgA and IgG receptors. We characterized memory cells from tonsils on the basis of both FCRL4 and FCRL5 expression, defining three subsets with distinct surface proteins and gene expression. Atypical FCRL4+FCRL5+ memory cells had the most discrete surface protein expression and were enriched in cell adhesion pathways, consistent with functioning as tissue-resident cells. Atypical FCRL4−FCRL5+ memory cells expressed transcription factors and immunoglobulin genes that suggest poised differentiation into plasma cells. Accordingly, the FCRL4−FCRL5+ memory subset was enriched in pathways responding to endoplasmic reticulum stress and IFN-γ. We reconstructed ongoing B-cell responses as lineage trees, providing crucial in vivo developmental context. Each memory subset typically maintained its lineage, denoting mechanisms enforcing their phenotypes. Classical FCRL4−FCRL5− memory cells were infrequently detected in lineage trees, suggesting the majority were in a quiescent state. FCRL4−FCRL5+ cells were the most represented memory subset in lineage trees, indicating robust participation in ongoing responses. Together, these differences suggest FCRL4 and FCRL5 are unlikely to be passive markers but rather active drivers of human memory B-cell development and function.
From intensive care to step-down units: Managing patients throughput in response to COVID-19
Authors: AGNOLETTI Vanni , RUSSO Emanuele , CIRCELLI Alessandro , BENNI Marco , BOLONDI Giuliano , MARTINO Costanza , SANTONASTASO Domenico P , BROGI Etrusca , PRATICÒ Beniamino , COCCOLINI Federico , FUGAZZOLA Paola , ANSALONI Luca , GAMBERINI Emiliano
Published: August 2020

Quality problem or issue

The on-going COVID-19 pandemic may cause the collapse of healthcare systems because of unprecedented hospitalization rates.

Initial assessment

A total of 8.2 individuals per 1000 inhabitants have been diagnosed with COVID-19 in our province. The hospital predisposed 110 beds for COVID-19 patients: on the day of the local peak, 90% of them were occupied and intensive care unit (ICU) faced unprecedented admission rates, fearing system collapse.

Choice of solution

Instead of increasing the number of ICU beds, the creation of a step-down unit (SDU) close to the ICU was preferred: the aim was to safely improve the transfer of patients and to relieve ICU from the risk of overload.

Implementation

A nine-bed SDU was created next to the ICU, led by intensivists and ICU nurses, with adequate personal protective equipment, monitoring systems and ventilators for respiratory support when needed. A second six-bed SDU was also created.

Evaluation

Patients were clinically comparable to those of most reports from Western Countries now available in the literature. ICU never needed supernumerary beds, no patient died in the SDU, and there was no waiting time for ICU admission of critical patients. SDU has been affordable from human resources, safety and economic points of view.

Lessons learned

COVID-19 is like an enduring mass casualty incident. Solutions tailored on local epidemiology and available resources should be implemented to preserve the efficiency and adaptability of our institutions and provide the adequate sanitary response.
Pharmacokinetics and renal safety of tenofovir alafenamide with boosted protease inhibitors and ledipasvir/sofosbuvir
Authors: Brooks Kristina M , Castillo-Mancilla Jose R , Morrow Mary , MaWhinney Samantha , Blum Joshua , Wyles David L , Rowan Sarah E , Ibrahim Mustafa E , Zheng Jia-Hua , Johnson Bethany , Gomez Joe , Choi Ye Ji , Cendali Francesca , Haas Hannah , Roon Laura , Bushman Lane R , Anderson Peter L , Kiser Jennifer J
Published: August 2020

Background

Ledipasvir/sofosbuvir increases tenofovir plasma exposures by up to 98% with tenofovir disoproxil fumarate (TDF), and exposures are highest with boosted PIs. There are currently no data on the combined use of the newer tenofovir prodrug, tenofovir alafenamide (TAF), boosted PIs and ledipasvir/sofosbuvir.

Objectives

To compare the plasma and intracellular pharmacokinetics and renal safety of TAF with ledipasvir/sofosbuvir when co-administered with boosted PIs.

Methods

Persons with HIV between 18 and 70 years and on a boosted PI with TDF were eligible. The study was comprised of four phases: (1) TDF 300 mg with boosted PI; (2) TAF 25 mg with boosted PI; (3) TAF 25 mg with boosted PI and ledipasvir/sofosbuvir; and (4) TAF 25 mg with boosted PI. Pharmacokinetic sampling, urine biomarker collection [urine protein (UPCR), retinol binding protein (RBP) and β2 microglobulin (β2M) normalized to creatinine] and safety assessments occurred at the end of each phase. Plasma, PBMCs and dried blood spots were collected at each visit.

Results

Ten participants were enrolled. Plasma tenofovir exposures were 76% lower and tenofovir-diphosphate (TFV-DP) concentrations in PBMCs increased 9.9-fold following the switch to TAF. Neither of these measures significantly increased with ledipasvir/sofosbuvir co-administration, nor did TAF plasma concentrations. No significant changes in estimated glomerular filtration rate or UPCR occurred, but RBP:creatinine and β2M:creatinine improved following the switch to TAF.

Conclusions

Ledipasvir/sofosbuvir did not significantly increase plasma tenofovir or intracellular TFV-DP in PBMCs with TAF. These findings provide reassurance that the combination of TAF, boosted PIs and ledipasvir/sofosbuvir is safe in HIV/HCV-coinfected populations.
β-Lactam antimicrobial pharmacokinetics and target attainment in critically ill patients aged 1 day to 90 years: the ABDose study
Authors: Lonsdale Dagan O , Kipper Karin , Baker Emma H , Barker Charlotte I S , Oldfield Isobel , Philips Barbara J , Johnston Atholl , Rhodes Andrew , Sharland Mike , Standing Joseph F
Published: August 2020

Background

The pharmacokinetics of β-lactam antibiotics in critical illness remain poorly characterized, particularly in neonates, children and the elderly. We undertook a pharmacokinetic study of commonly used β-lactam antibiotics in critically ill patients of all ages. The aims were to produce a whole-life β-lactam pharmacokinetic model and describe the extent to which standard doses achieve pharmacokinetic/pharmacodynamic targets associated with clinical cure.

Patients and methods

A total of 212 critically ill participants with an age range from 1 day (gestational age 24 weeks) to 90 years were recruited from a UK hospital, providing 1339 pharmacokinetic samples. Population pharmacokinetic analysis was undertaken using non-linear mixed-effects modelling (NONMEM) for each drug. Pooled data were used to estimate maturation and decline of β-lactam pharmacokinetics throughout life.

Results

Pharmacokinetic models for eight drugs were described, including what is thought to be the first benzylpenicillin model in critically ill adults. We estimate that 50% of adult β-lactam clearance is achieved by 43 weeks post-menstrual age (chronological plus gestational age). Fifty percent of decline from peak adult clearance occurs by 71 years. Paediatric participants were significantly less likely than adults to achieve pharmacokinetic/pharmacodynamic targets with standard antibiotic doses (P < 0.01).

Conclusions

We believe this to be the first prospective whole-life antibiotic pharmacokinetic study in the critically ill. The study provides further evidence that standard antibiotic doses fail to achieve pharmacokinetic/pharmacodynamic targets associated with clinical success in adults, children and neonates. Maturation and decline parameters estimated from this study could be adopted as a standard for future prospective studies.
Colonization with multiresistant bacteria in acute hospital care: the association of prior antibiotic consumption as a risk factor
Authors: Dualleh Nasra , Chanchiri Iman , Skjøt-Arkil Helene , Pedersen Andreas Kristian , Rosenvinge Flemming S , Johansen Isik Somuncu
Published: August 2020

Background

Antibiotic resistance poses a worldwide threat and knowledge concerning risk factors for colonization with multiresistant bacteria (MRB) is limited.

Objectives

To examine the impact of prior antibiotic consumption on MRB colonization, with focus on type of antibiotic and timeline between antibiotic prescription and MRB colonization.

Methods

A nationwide case–control study was conducted and adults visiting emergency departments were invited to participate. All patients were swabbed in the throat, nose and rectum, and analysed for colonization with ESBL-producing Enterobacteriaceae (ESBL-E), MRSA, carbapenemase-producing enterobacteria and VRE. Antibiotic history 2 years prior to enrolment was collected at an individual level through a national register. Multivariate analyses were performed to examine the association between antibiotic consumption and MRB status. A subgroup analysis of ESBL-E-colonized cases was made.

Results

We included 256 patients colonized with MRB and 4763 controls. In the 2 years prior to study inclusion, 77% of cases and 68% of controls had at least one antibiotic prescription (P = 0.002). We found a significant increase in risk of colonization with ESBL-E if penicillins (OR = 1.58–1.65) or fluoroquinolones (OR = 2.25–6.15) were prescribed. The analysis of all MRB-colonized patients showed similar results. An assessment of the timeline showed a significant increase in risk of colonization up to 2 years after exposure to penicillins, fluoroquinolones and macrolides.

Conclusions

The prevalence of ESBL-E colonization was related to fluoroquinolone, macrolide and penicillin consumption for at least 2 years after antibiotic treatment.
In vitroactivity of rifabutin against 293 contemporary carbapenem-resistantAcinetobacter baumanniiclinical isolates and characterization of rifabutin mode of action and resistance mechanisms
Authors: Trebosc Vincent , Schellhorn Birgit , Schill Julian , Lucchini Valentina , Bühler Jacqueline , Bourotte Marilyne , Butcher Jonathan J , Gitzinger Marc , Lociuro Sergio , Kemmer Christian , Dale Glenn E
Published: August 2020

Background

Rifabutin, an oral drug approved to treat Mycobacterium avium infections, demonstrated potent activity against Acinetobacter baumannii in nutrient-limited medium enabled by rifabutin cellular uptake through the siderophore receptor FhuE.

Objectives

To determine rifabutin in vitro activity and resistance mechanisms in a large panel of A. baumannii isolates.

Methods

Two hundred and ninety-three carbapenem-resistant A. baumannii clinical isolates collected from Europe, the USA and Asia during 2017–19 were used for MIC determination. Sequencing/genotyping of fhuE, rpoB and arr-2 genes in isolates with elevated rifabutin MIC combined with genetic engineering and gene expression quantification was used to characterize rifabutin’s mode of action and resistance mechanisms.

Results

Rifabutin showed excellent activity on the strain panel, with an MIC50/90 of 0.008/1 mg/L, and was superior to all other antibiotics tested, including colistin, tigecycline and cefiderocol (MIC90 of 8 mg/L). Rifabutin remained active on resistant subpopulations, including strains resistant to the siderophore–drug conjugate cefiderocol (MIC90 of 2 mg/L, n = 23). At least two independent resistance mechanisms were required to abolish rifabutin activity, which is in line with the dose-dependent mutational resistance frequency reaching 10−9 at rifabutin concentrations at or above 2 mg/L.

Conclusions

This study demonstrated the potent activity of rifabutin against carbapenem-resistant A. baumannii. We propose that FhuE-mediated active uptake of rifabutin enables activity against rifampicin-resistant isolates. To achieve clinically meaningful strain coverage and to avoid rapid resistance development, rifabutin concentrations ≥2 mg/L are required, something rifabutin oral formulations cannot deliver.
Time- and Site-Dependent Postmortem Redistribution of Antidepressants and Neuroleptics in Blood and Alternative Matrices
Authors: Brockbals Lana , Staeheli Sandra N , Gascho Dominic , Ebert Lars C , Kraemer Thomas , Steuer Andrea E
Published: August 2020

Postmortem redistribution (PMR) leads to challenges in postmortem case interpretation. Particularly antidepressants and neuroleptics are expected to undergo PMR based on their physico-chemical properties. For the current study, time- and site-dependent PMR of 20 antidepressants and neuroleptics were investigated in humans (authentic cases); five of which are discussed in detail (citalopram, mirtazapine, quetiapine, risperidone and venlafaxine) along with two metabolites (9-OH-risperidone and O-desmethylvenlafaxine). Blood [femoral (pB) and heart blood (HB)] and tissue biopsy samples (lung, kidney, liver, spleen, thigh muscle and adipose tissue) were collected upon admission to the institute utilizing a computed tomography-guided sample collection workflow (t1). Approximately 24 h later (t2; mean 23 ± 9.3 h), samples from the same body regions were collected manually. Liquid chromatography–tandem mass spectrometry was used for quantification. Most antidepressants and neuroleptics showed significant time-dependent concentration changes indicating the occurrence of PMR. For the first time, two phases of redistribution in pB for quetiapine were proposed (concentration decreases in the early postmortem phase, followed by concentration increases) and contrasting existing literature, both concentration increases and decreases in pB overtime were observed for risperidone and 9-OH-risperidone. Venlafaxine and its metabolite only showed minimal concentration changes, while citalopram exhibited a trend for concentration increases and mirtazapine for concentration decreases in pB overtime. Based on time-dependent tissue data, passive diffusion processes along the muscle-to-pB, liver-to-HB and lung-to-HB concentration gradients could be proposed along with bacterial degradation. Overall, no case interpretation had to be adjusted, which suggests that PMR changes of antidepressants and neuroleptics do not seem to be relevant for forensic case interpretation within the 24 h period that was investigated. However, limitations of the current study (e.g., temperature-controlled storage of the bodies) could have led to an underestimation of occurring postmortem changes, hence, interpretation of postmortem results should always be conducted with care, considering PMR phenomena and inter-individual variability.
Determining the Effect of Postharvest Cold Storage Treatment on the Survival of Immature Drosophila suzukii (Diptera: Drosophilidae) in Small Fruits
Authors: Kraft Laura J , Yeh D Adeline , Gómez Miguel I , Burrack Hannah J
Published: August 2020

We evaluated the effect of postharvest cold storage temperature (0.0–2.2°C) and duration (3–5 d) on pupal emergence of single life stage populations of laboratory-generated Drosophila suzukii (Matsumura) and mixed-age populations collected in the field from blackberries, blueberries, strawberries, and raspberries. For field-infested fruit, cold storage at any temperature and duration resulted in less pupal emergence compared with the control held at 20°C, but D. suzukii subjected to higher temperatures and shorter storage durations in caneberries had higher survival. When a single life stage of D. suzukii was exposed to cold storage, pupal emergence was significantly reduced across all fruit types held at 0°C and for most life stages and fruit types held at 1.5 and 2.2°C, dependent on the substrate. Freshly laid eggs exposed to cold storage produced the lowest pupal emergence. Our results suggest using cold storage treatment is an effective postharvest management strategy for small-fruit growers to use on-farm as part of an integrated program to manage D. suzukii infestation. An economic assessment was made to examine the profit implications of an investment in cold storage units to counter pest pressure. Results suggest that investment in a cold storage unit would breakeven in about 4 yr. On farms that already have cold storage installed, we estimated a $0.11/kg decrease in blueberry market price for holding fruit for 3 d. Together, this cost assessment will provide growers with the knowledge to make decisions based on infestation risk and the seasonal sale price of blueberries.