bluuebunny/crossref_metadata_2025 huggingface dataset:
The Path to Eldership: Results From a Contemporary Indigenous Australian Community
Authors: Eades Owen , Toombs Maree R , Cinelli Renata , Easton Caitlin , Hampton Ron , Nicholson Geoffrey C , McCabe Marita P , Busija Lucy
Published: May 2021

Background and Objectives

Traditionally, Elders have held a unique social position within Indigenous Australian communities. This study aimed to identify the characteristics of Indigenous Elders that distinguish them from other people in their community.

Research Design and Methods

Using a community-based participatory research approach, the study was conducted in a regional Indigenous community in Southeast Queensland. The design and data collection methods were informed through a community forum, known as a “Yarning Circle.” One-on-one semistructured interviews and focus groups with community members were carried out by Indigenous researchers. Data were analyzed in NVivo software, using thematic analysis (TA), with themes derived directly from data.

Results

Fifty individuals participated in the study. The participants’ median age was 45 years (range 18–76 years) and 31 (62%) were female. TA identified 3 overarching themes related to Elders’ attributes: (a) distinguishing characteristics of Elders (subthemes of respect, leadership, reciprocity, life experience, approachability, connection to traditional culture, and transmitting knowledge through generations); (b) how one becomes an Elder (earnt eldership, permanency of eldership, mentors and role models, age); and (c) threats to Elders’ influence (intergenerational gap, community disconnect, and cultural trauma).

Discussion and Implications

Our results build a greater understanding of the contemporary role of Indigenous Australian Elders, which will inform the development of future interventions directed at strengthening Elders’ role in their communities.
Is diminished ovarian reserve a risk factor for miscarriage? Results of a systematic review and meta-analysis
Authors: Busnelli Andrea , Somigliana Edgardo , Cirillo Federico , Levi-Setti Paolo Emanuele
Published: May 2021

BACKGROUND

Anti-Müllerian hormone (AMH) serum concentration and antral follicle count (AFC), as measured by transvaginal ultrasonography, accurately reflect the antral follicle pool. However, AMH and AFC association with fertility surrogates (i.e. age at menopause, probability of conceiving naturally and ART success rate) is questioned. Miscarriage is often considered an alternative measure of reproductive capacity. Nonetheless, the impact of diminished ovarian reserve (DOR) on miscarriage incidence remains an understudied and unresolved issue.

OBJECTIVE AND RATIONALE

The aim of this systematic review and meta-analysis was to elucidate associations between DOR and miscarriage risk, both in women who conceived naturally and in those who achieved pregnancy through ART.

SEARCH METHODS

Relevant studies were identified by a systematic search in PubMed, MEDLINE, Embase and Scopus, from database inception to 1 March 2021. Studies were included only if all the following conditions were met: DOR was defined using serum AMH concentration or AFC; miscarriage rate was reported separately for different groups of women categorized according to the AMH and/or AFC level; authors reported either the rate of intrauterine pregnancy loss before 22 weeks of gestation or enough data were available to calculate it.

OUTCOMES

From a total of 347 publications initially identified, 16 studies were included. Pooled results from 13 retrospective studies focusing on ART pregnancies showed a significantly higher rate of miscarriage in women with a low AMH, as compared to women with a medium or high serum AMH concentration (12 042 women, random effects model, odds ratio (OR) 1.35; 95% CI, 1.10–1.66; P = 0.004; I2=50%). The only prospective study on ART pregnancies failed to show any association (61 women, risk ratio (RR) 2.95; 95% CI, 0.66–3.18; P = 0.16). Data from two prospective studies, which included naturally conceived pregnancies, showed a significantly increased miscarriage risk for women with low serum AMH. However, these data could not undergo meta-analysis owing to differing study designs. Using three retrospective studies, we observed an association between low AFC and miscarriage incidence (three retrospective studies on ART pregnancies, random effects model, OR 1.81; 95% CI, 1.02–3.21; P = 0.04; I2=64%).

WIDER IMPLICATIONS

Our meta-analysis findings suggest that within the DOR patient subgroup, serum AMH and AFC biomarker levels may correlate with both the quantitative and qualitative aspects of ovarian reserve. However, owing to study limitations, the aetiology of this effect remains unclear and we are unable to define a causal relationship between DOR and increased miscarriage or to provide clinical recommendations based on this information. However, if confirmed by future well-designed studies, these findings would be profoundly informative for guiding women in family planning decisions.
Sectarian securitization in the Middle East and the case of Israel
Authors: Del Sarto Raffaella A
Published: May 2021

Focusing on the politics of sectarianism in the Middle East after the Arab uprisings, this article advances two main claims. First, it identifies the current climate of insecurity in the region amid major geopolitical shifts as a key condition that allows political leaders to present sectarian identities as being under (existential) threat. However, a heightened sense of insecurity not only acts as an enabling condition but is also the outcome of these sectarian securitization strategies. The ‘politics of fear’ may thus trigger a self-sustaining mechanism, or a vicious cycle. Second, as sectarian securitization has intensified in Israel since the early 2000s, the article discusses the vicious cycle of securitized sectarianism in the case of Israel in a comparative perspective. By drawing the attention to insecurity (or the sense thereof) as a key enabling condition against the backdrop of major disruptive events, and by bringing the case of Israel into the picture, the article contributes to our understanding of the current structure of regional politics in the Middle East. It concludes by reflecting on the impact of sectarian securitization on the region's conflict potential and the comparability of the Israeli case with those of other states in the region.
Enforcing copyright through antitrust? The strange case of news publishers against digital platforms
Authors: Colangelo Giuseppe
Published: May 2021

The emergence of the multi-sided platform business model has had a profound impact on the news publishing industry. By acting as gatekeepers to news traffic, large online platforms appear to be unavoidable trading partners for news businesses and may exert substantial bargaining power in their dealings. Concerns have been raised that this bargaining power imbalance may threaten the viability of publishers’ businesses. Notably, digital infomediaries are accused of capturing a huge share of the advertising revenue by free-riding on the investments made in producing news content. Moreover, by affecting the monetization of news, the dominance of some online platforms is deemed to have contributed to the decline of trustworthy sources of news. Against this background, governments have been urged to intervene in order to ensure the sustainability of the publishing industry. The EU has decided to address publishers’ concerns by introducing an additional layer of copyright as a means to encourage cooperation between press publishers and online services. And the French Competition Authority has recently accused Google of adopting a display policy aimed at frustrating the objective of the domestic law implementing the EU legislation, hence requiring Google to conduct negotiations in good faith with publishers and news agencies on the remuneration for the reuse of their protected content. The Australian Competition and Consumer Commission has instead embraced a regulatory approach, developing a mandatory bargaining code. The aim of this article is to analyse the different solutions advanced in order to assess their economic and legal justifications as well as their effectiveness.
Agency, Free Will, Self-Constitution: New Concepts for Historians of German-Jewish History between 1914 and 1938?
Authors: Kauders Anthony D
Published: May 2021

This article discusses recent work on German-Jewish agency between 1914 and 1938. To find out whether ‘agency’ might be a helpful category for examining the crises facing Central European Jewry in this period, the article addresses the subject from the perspectives of individual and collective agency, applying classifications that philosophers have employed to make sense of human conduct. As I hope to show, these delimitations are only a preliminary step in trying to determine the explanatory power of agency. Whether the latter can serve as a tool in future work on modern German-Jewish history depends on the suitability of more specific philosophies of agency. Here the work of Christine Korsgaard and especially Michael Bratman may prove helpful in reflecting both on the self-understanding of German Jews in the first decades of the twentieth century and on their ‘freedom of action’ once this self-understanding was called into question. There is reason to see planning structures—grounded in the diachronic organization of our temporally extended selves—as basic to our individual and collective agency. Without ‘planning agency’, I will argue, ‘agency’ refers to mere action or choice.
Successful Use of Telemedicine Infectious Diseases Consultation With an Antimicrobial Stewardship-Led Staphylococcus aureus Bacteremia Care Bundle
Authors: Meredith Jacqueline , Onsrud Jennifer , Davidson Lisa , Medaris Leigh Ann , Kowalkowski Marc , Fischer Kristin , Priem Jennifer , Leonard Michael , McCurdy Lewis
Published: May 2021

Background

Telemedicine (TM) programs can be implemented to deliver specialty care through virtual platforms and overcome geographic/resource constraints. Few data exist to describe outcomes associated with TM-based infectious diseases (ID) management. The purpose of this study was to compare outcomes associated with TM and onsite standard-of-care (SOC) ID consultation after implementation of an antimicrobial stewardship (AMS)-led Staphylococcus aureus bacteremia (SAB) bundle.

Methods

A retrospective cohort study was conducted on the effects of a SAB bundle comparing ID consult delivery (SOC or TM) at 10 US hospitals within Atrium Health in adult patients admitted from September 2016 through December 2017. The type of ID consult provided was based on the admitting hospital; no hospital had both modalities. Bundle components included the following: (1) ID consult, (2) appropriate antibiotics, (3) repeat blood cultures until clearance, (4) echocardiogram obtainment, and (5) appropriate antibiotic duration. The AMS facilitated bundle initiation and compliance. The primary outcome was bundle adherence between groups. Differences in clinical outcomes were also assessed.

Results

We evaluated 738 patients with SAB (576 with SOC, 162 with TM ID). No differences were observed in overall bundle adherence (SOC 86% vs TM 89%, P = .33). In addition, no significant differences resulted between groups for hospital mortality, 30-day SAB-related readmission, persistent bacteremia, and culture clearance. Groups did not differ in 30-day mortality when controlling for demographics, bacteremia source, and physiological measures with multivariable logistic regression.

Conclusions

Our findings provide evidence to support effective use of TM ID consultation and AMS-led care bundles for SAB management in resource-limited settings.
Development of a new wideband heterodyne receiver system for the Osaka 1.85 m mm–submm telescope: Receiver development and the first light of simultaneous observations in 230 GHz and 345 GHz bands with an SIS-mixer with 4–21 GHz IF output
Authors: Masui Sho , Yamasaki Yasumasa , Ogawa Hideo , Kondo Hiroshi , Yokoyama Koki , Matsumoto Takeru , Minami Taisei , Okawa Masanari , Konishi Ryotaro , Kawashita Sana , Konishi Ayu , Nakao Yuka , Nishimoto Shimpei , Yoneyama Sho , Ueda Shota , Hasegawa Yutaka , Fujita Shinji , Nishimura Atsushi , Kojima Takafumi , Uemizu Kazunori , Kaneko Keiko , Sakai Ryo , Gonzalez Alvaro , Uzawa Yoshinori , Onishi Toshikazu
Published: May 2021

We have developed a wideband receiver system for simultaneous observations in CO lines of J = 2–1 and J = 3–2 transitions using the Osaka 1.85 m mm–submm telescope. As a frequency separation system, we developed multiplexers that connect three types of diplexers, each consisting of branch-line couplers and high-pass filters. The radio frequency (RF) signal is eventually distributed into four frequency bands, each of which is fed to a superconductor–insulator–superconductor (SIS) mixer. The RF signal from the horn is divided into two frequency bands by a wideband diplexer with a fractional bandwidth of $56\%$, and then each frequency band is further divided into two bands by each diplexer. The developed multiplexers were designed, fabricated, and characterized using a vector network analyzer. The measurement results showed good agreement with the simulation. The receiver noise temperature was measured by connecting the SIS-mixers, one of which has a wideband 4–21 GHz intermediate frequency (IF) output. The receiver noise temperatures were measured to be ∼70 K in the 220 GHz band, ∼100 K in the 230 GHz band, 110–175 K in the 330 GHz band, and 150–250 K in the 345 GHz band. This receiver system has been installed on the 1.85 m telescope at the Nobeyama Radio Observatory. We succeeded in simultaneous observations of six CO isotopologue lines with the transitions of J = 2–1 and J = 3–2 toward the Orion KL as well as on-the-fly mappings toward the Orion KL and W 51.
The Atiyah–Patodi–Singer index theorem from the axial anomaly
Authors: Kobayashi Shun K , Yonekura Kazuya
Published: May 2021

We give a very simple derivation of the Atiyah–Patodi–Singer (APS) index theorem and its small generalization by using the path integral of massless Dirac fermions. It is based on Fujikawa’s argument for the relation between the axial anomaly and the Atiyah–Singer index theorem, and only a minor modification of that argument is sufficient to show the APS index theorem. The key ingredient is the identification of the APS boundary condition and its generalization as physical state vectors in the Hilbert space of the massless fermion theory. The APS $\eta$-invariant appears as the axial charge of the physical states.
ACTIVITY CONCENTRATION ESTIMATION IN AUTOMATED KIDNEY SEGMENTATION BASED ON CONVOLUTION NEURAL NETWORK METHOD FOR 177LU–SPECT/CT KIDNEY DOSIMETRY
Authors: Khan Jehangir , Rydèn Tobias , Van Essen Martijn , Svensson Johanna , Bernhardt Peter
Published: May 2021

For 177Lu-DOTATATE treatments, dosimetry based on manual kidney segmentation from computed tomography (CT) is accurate but time consuming and might be affected by misregistration between CT and SPECT images. This study develops a convolution neural network (CNN) for automated kidney segmentation that accurately aligns CT segmented volume of interest (VOI) to the kidneys in SPECT images. The CNN was trained with SPECT/CT images performed over the abdominal area of 137 patients treated with 177Lu-DOTATATE. Activity concentrations in automated and manual segmentations were strongly correlated for both kidneys (r > 0.96, p < 0.01) in the testing cohort (n = 20). The Bland–Altman analyses demonstrated higher accuracy for the CNN segmentation compared to the manual segmented kidneys without VOI adjustment. The CNN demonstrated a potential for accurate kidney segmentation. The CNN was a fast and robust approach for assessment of activity concentrations in SPECT images, and performed equally well as the manual segmentation method.
Shrink, weighing accuracy, and weighing precision of mineral supplement in five commercial dairies in the Western United States
Authors: Arce-Cordero J A , Archibeque S L , Faciola A P
Published: May 2021

Shrink, accuracy, and precision of ingredient weighing are critical factors of efficiency in TMR-fed dairy systems. Those factors have been evaluated for major feeds; however, we are not aware of any reports for mineral supplement. Farms commonly mix mineral supplement with other low-inclusion ingredients into a premix which is used later as a single ingredient for TMR formulation. Our objectives were to evaluate shrink, weighing accuracy, and weighing precision of mineral supplement during premix formulation, and variation in concentration of minerals in mineral supplement and TMR, in five large dairies in the Western United States. We used the automated weight-tracking system at each farm to account for all the mineral supplement loaded into the mixing-wagon and collected samples of mineral supplement and TMR from time of mineral supplement delivery at the farm until 100% of it was consumed. Mean, standard deviation and coefficient of variation (CV) for each variable were calculated with SAS 9.4. Average shrink was estimated at 2.0% for mineral supplement during storage and loading, ranging from 0.37% to 3.25%. Mineral supplement weighing deviation from the targeted amount was 1.54% on average for the five dairies with a 95% CV. Mineral composition of mineral supplements averaged 11.3%, 0.27%, and 3.16% for Ca, P, and Mg, and 215, 881, and 1533 ppm for Cu, Mn, and Zn, respectively. Mineral compositions in TMR averaged 0.84%, 0.41%, and 0.37% for Ca, P, and Mg, respectively; and 15.1, 71, and 94.5 ppm for Cu, Mn, and Zn, respectively. The CV of all minerals except Ca, were larger for mineral supplement than TMR, and with the exception of P in mineral supplement, CV of trace minerals were larger than CV values for macro minerals. Our shrink estimates for mineral supplement represent an initial approximation to this issue. Results of our weighing deviation analysis suggest some room for improvement on the precision of weighing mineral supplement at the time when premix is prepared at the farm, which could improve consistency in chemical composition of the premix and consequently reduce the variation (CV values) of mineral concentrations in TMR.
Radial stem growth dynamics and phenology of a multi-stemmed species (Corylus avellanaL.) across orchards in the Northern and Southern hemispheres
Authors: Pasqualotto Gaia , Ascari Lorenzo , Bicego Giovanni , Carraro Vinicio , Huerta Eloy Suarez , De Gregorio Tommaso , Siniscalco Consolata , Anfodillo Tommaso
Published: May 2021

Climate change and the global economy impose new challenges in the management of food-producing trees and require studying how to model plant physiological responses, namely growth dynamics and phenology. Hazelnut (Corylus avellana L.) is a multi-stemmed forest species domesticated for nut production and now widely spread across different continents. However, information on stem growth and its synchronization with leaf and reproductive phenology is extremely limited. This study aimed at (i) defining the sequencing of radial growth phases in hazelnut (onset, maximum growth and cessation) and the specific temperature triggering stem growth; and (ii) combining the stem growth phases with leaf and fruit phenology. Point dendrometers were installed on 20 hazelnut trees across eight orchards distributed in the Northern and Southern hemisphere during a period of three growing seasons between 2015 and 2018. The radial growth variations and climatic parameters were averaged and recorded every 15 min. Leaf and reproductive phenology were collected weekly at each site. Results showed that stem radial growth started from day of year 84 to 134 in relation to site and year but within a relatively narrow range of temperature (from 13 to 16.5 °C). However, we observed a temperature-related acclimation in the cultivar Tonda di Giffoni. Maximum growth always occurred well before the summer solstice (on average 35 days) and before the maximum annual air temperatures. Xylogenesis developed rapidly since the time interval between onset and maximum growth rate was about 3 weeks. Importantly, the species showed an evident delay of stem growth onset with respect to leaf emergence (on average 4–6 weeks) rarely observed in tree species. These findings represent the first global analysis of radial growth dynamics in hazelnut, which is an essential step for developing models on orchard functioning and management on different continents.
PthAW1, a Transcription Activator-Like Effector ofXanthomonas citrisubsp.citri, Promotes Host-Specific Immune Responses
Authors: Teper Doron , Xu Jin , Pandey Sheo Shankar , Wang Nian
Published: May 2021

Citrus canker disease caused by Xanthomonas citri subsp. citri is one of the most destructive diseases in citrus. X. citri subsp. citri pathotypes display different host ranges. X. citri subsp. citri strain A (XccA) causes canker disease in most commercial citrus varieties, whereas strain AW (XccAW), which is genetically similar to XccA, infects only lime and alemow. Understanding the mechanism that determines the host range of pathogens is critical to investigating and utilizing host resistance. We hypothesized that XccAWwould undergo mutations in genes that restrict its host range when artificially inoculated into incompatible citrus varieties. To test this hypothesis, we used an experimental evolution approach to identify phenotypic traits and genetic loci associated with the adaptation of XccAWto incompatible sweet orange. Repeated inoculation and reisolation cycles improved the ability of three independent XccAWstrains to colonize sweet orange. Adapted XccAWstrains displayed increased expression of type III secretion system and effector genes. Genome sequencing analysis indicated that two of the adapted strains harbored mutations in pthAW1, a transcription activator-like effector (TALE) gene, that corresponded to the removal of one or two repeats from the central DNA-binding repeat region. Introduction of the original but not the adapted pthAW1 variants into XccAabolished its ability to cause canker symptoms in sweet orange, Meyer lemon, and clementine but not in other XccAW-resistant citrus varieties. The original pthAW1, when expressed in XccA, induced ion leakage and the expression of pathogenesis-related genes but had no effect on CsLOB1 expression in sweet orange. Our study has identified a novel host-specific avirulence TALE and demonstrated active adaptive rearrangements of the TALE repeat array during host adaptation.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Genomics- and Machine Learning-Accelerated Discovery of Biocontrol Bacteria
Authors: Biggs Matthew B. , Craig Kelly , Gachango Esther , Ingham David , Twizeyimana Mathias
Published: May 2021

Microorganisms with antimicrobial activity have been used to successfully control various plant pathogens. The discovery of organisms with protective activity depends on empirical screenings to assess microbial activity against pathogens of interest. Machine learning can accelerate the discovery process by making screening and, thus, discovery more efficient. We developed a novel machine-learning workflow to identify genomic features associated with fungicidal activity of bacteria, and leveraged those genomic features to discover additional bacteria with the desired activity. We applied our workflow to discover solutions to two problematic fungal diseases: sorghum anthracnose and black sigatoka of banana. These diseases are problematic worldwide, with a particularly devastating impact on small-holder farmers in Sub-Saharan Africa. We screened a total of 1,227 bacterial isolates for antifungal activity against these pathogens using detached-leaf methods and identified 72 taxonomically diverse isolates with robust activity against one or both of these pathogens. We identified biosynthetic gene clusters associated with activity against each pathogen. Machine learning improved the discovery rate of our screen by threefold, and led to the discovery of a taxonomic group in which fungicidal activity has never been reported. This work highlights the wealth of biocontrol mechanisms available in the microbial world for management of fungal pathogens, generates opportunities for future characterization of novel fungicidal mechanisms, and provides a set of genomic features and models for discovering additional bacterial isolates with activity against these two pathogens. Finally, our workflow generalizes to any discovery effort where genomic information is available to guide candidate selection.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Delivery of ERAS Care in an Academic Hospital
Authors: Roth Eve M. , Wong Daniel J. , Poylin Vitaliy Y. , Messaris Evangelos , Cataldo Thomas E.
Published: May 2021

Enhanced Recovery after Surgery (ERAS) pathways in colorectal surgery improve outcomes and reduce disparities, but pathway adherence rates are variable. Sustainability of adherence following initial implementation, particularly in academic settings with trainee involvement, is underexplored. This study measures and describes ERAS adherence for 163 consecutive patients undergoing elective colorectal resection in an academic colorectal surgery department with a well-established ERAS pathway. Providers, including residents and nursing staff, were surveyed regarding pathway knowledge and obstacles to adherence. Adherence was higher preoperatively (80%) and intraoperatively (93%) than postoperatively (61%). Opioid-sparing analgesia and bowel motility agents were underdosed on up to 63% of hospital days, without clinical rationale in ≥50% of cases. Providers cited peer teaching (71%) as the primary source of pathway knowledge and identified individual surgeon preferences as an obstacle to adherence. Formalized ERAS pathway education, communication, and coordination among attending physicians are needed to reduce provider-driven deviation in an academic setting.
Functional Outcomes and Their Association With Physical Performance in Mechanically Ventilated Coronavirus Disease 2019 Survivors at 3 Months Following Hospital Discharge: A Cohort Study
Authors: van Gassel Rob J. J. , Bels Julia , Remij Loes , van Bussel Bas C. T. , Posthuma Rein , Gietema Hester A. , Verbunt Jeanine , van der Horst Iwan C. C. , Olde Damink Steven W. M. , van Santen Susanne , van de Poll Marcel C. G.
Published: May 2021

OBJECTIVES:

We performed a comprehensive health assessment in mechanically ventilated coronavirus disease 2019 survivors to assess the impact of respiratory and skeletal muscle injury sustained during ICU stay on physical performance at 3 months following hospital discharge.

DESIGN:

Preregistered prospective observational cohort study.

SETTING:

University hospital ICU.

PATIENTS:

All mechanically ventilated coronavirus disease 2019 patients admitted to our ICU during the first European pandemic wave.

MEASUREMENTS AND MAIN RESULTS:

At 3 months after hospital discharge, 46 survivors underwent a comprehensive physical assessment (6-min walking distance, Medical Research Council sum score and handgrip strength), a full pulmonary function test, and a chest CT scan which was used to analyze skeletal muscle architecture. In addition, patient-reported outcomes measures were collected. Physical performance assessed by 6-minute walking distance was below 80% of predicted in 48% of patients. Patients with impaired physical performance had more muscle weakness (Medical Research Council sum score 53 [51–56] vs 59 [56–60]; p < 0.001), lower lung diffusing capacity (54% [44–66%] vs 68% of predicted [61–72% of predicted]; p = 0.002), and higher intermuscular adipose tissue area (p = 0.037). Reduced lung diffusing capacity and increased intermuscular adipose tissue were independently associated with physical performance.

CONCLUSIONS:

Physical disability is common at 3 months in severe coronavirus disease 2019 survivors. Lung diffusing capacity and intermuscular adipose tissue assessed on CT were independently associated with walking distance, suggesting a key role for pulmonary function and muscle quality in functional disability.
Thinking through the multimodal treatment of localized oesophageal cancer: the point of view of the surgeon
Authors: Pucher Philip H. , Wijnhoven Bas P.L. , Underwood Timothy J. , Reynolds John V. , Davies Andrew R.
Published: May 2021

Purpose of review

This review examines current developments and controversies in the multimodal management of oesophageal cancer, with an emphasis on surgical dilemmas and outcomes from the surgeon's perspective.

Recent findings

Despite the advancement of oncological neoadjuvant treatments, there is still no consensus on what regimen is superior. The majority of patients may still fail to respond to neoadjuvant therapy and suffer potential harm without any survival advantage as a result. In patients who do not respond, adjuvant therapy is still often recommended after surgery despite any evidence for its benefit. We examine the implications of different regimens and treatment approaches for both squamous cell cancer and adenocarcinoma of the oesophagus.

The efficacy of neoadjuvant treatment is highly variable and likely relates to variability of tumour biology. Ongoing work to identify responders, or optimize treatment on an individual patient, should increase the efficacy of multimodal therapy and improve patient outcomes.
Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study
Authors: Shi Yuan-Kai , Hong Xiao-Nan , Yang Jian-Liang , Xu Wei , Huang Hui-Qiang , Xiao Xiu-Bin , Zhu Jun , Zhou Dao-Bin , Han Xiao-Hong , Wu Jian-Qiu , Zhang Ming-Zhi , Jin Jie , Ke Xiao-Yan , Li Wei , Wu De-Pei , Yang Shen-Miao , Du Xin , Jia Yong-Qian , Liu Ai-Chun , Liu Dai-Hong , Shen Zhi-Xiang , Zhang Lian-Sheng , James Leonard , Hellriegel Edward
Published: May 2021

Background:

Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment.

Methods:

This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR.

Results:

A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%–81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities.

Conclusion:

Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients.

Clinical trial registration:

ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621
Determining pediatric hypertension criteria: concordance between observed physician methods and guideline-recommended methods
Authors: Turer Christy B. , Doney Analise , Bowen Michael E. , Menzies Christopher , Gheen William T. , Bhat Deepa , Fish Jason , Barlow Sarah E. , Skinner Celette S. , Lehmann Christoph U.
Published: May 2021

Objective:

To determine and evaluate the accuracy of methods physicians use to detect diagnostic criteria for pediatric hypertension [hypertensive blood pressures (BPs) on three or more occasions] in electronic health records (EHRs).

Methods:

Methods used by pediatric-trained physicians (n = 12) to detect diagnostic criteria for hypertension in a simulation using a child's EHR data were directly observed, timed, and evaluated for accuracy. All physicians were given the same information regarding diagnostic criteria to eliminate knowledge gaps. Then, computer modeling and EHR data from 41 654 3–18-year-olds were used to simulate and compare the accuracy of detecting hypertension criteria using an observed-shorthand method vs. the guideline-recommended/gold-standard method.

Results:

No physician used the guideline-recommended method of determining multiple time-of-care hypertension thresholds for child age/height at the time of each BP measure. One physician estimated the child's BP diagnosis without computing thresholds; 11 of 12 physicians determined the child's hypertension threshold from age/height data at the time of a current visit and applied/imputed this threshold to BP measured at all visits (current-visit threshold used to assess historical-visit BPs) to detect three separate BP elevations. Physicians took 2.3 min (95% confidence interval, 1.5–3.0) to declare a diagnosis. Sensitivity was 83.1% when applying the current-visit threshold to detect the guideline-recommended-BP-threshold diagnosis using EHR data. Specificity and positive-predictive/negative-predictive values ranged from 98.5 to 99.9%.

Conclusion:

Physicians applied a shorthand method to evaluate pediatric BPs. Computer-simulated comparison of the shorthand and guideline methods using clinical data suggest the shorthand method could yield an inaccurate impression of a child's BP history in 17% of pediatric ambulatory visits.
Radon Concentrations in a Nuclear Reactor Center in Brazil
Authors: Cardoso da Silva Paulo Sergio , de Campos Marcia Pires , Mohamad El Hajj Thammiris , de Lima Reis Guilherme
Published: May 2021

Radiation workers are normally exposed to doses resulting from their day-to-day activities. Besides that, background radiation, such as radon, can contribute to the exposure rates. The radionuclide 222Rn is a noble gas belonging to the uranium series, and its indoor concentration in the air depends on the exhalation from surrounding soil and the exhalation from building materials. Radon exhaling from porous building materials containing high uranium concentrations can become a significant exposure factor in areas with limited ventilation. The objective of this study was to evaluate the 222Rn concentrations in the radiochemistry and radiometric laboratories in the nuclear reactor building of the Nuclear Reactor Center (CERPq) located in the Institute of Nuclear and Energy Research (IPEN), São Paulo, Brazil. Measurements were done using a Radon Gas Monitor, model RAD7, equipped with a solid-state alpha detector. A passive method (SSNTD) was also used, consisting of square pieces of C-39 foils (2.5 cm × 2.5 cm) placed within small diffusion chambers. The CR-39 detectors were etched in KOH 30% solution at 80 °C for 5.5 h in a constant-temperature bath. After etching, the detectors were washed, dried, and scanned using a microscope to obtain the track density measurements. The activity concentrations measured with both techniques varied from 52 to 103 Bq m−3 in the studied areas of the CERPq. These values may be compared to the reference level of 100 Bq m−3 established by the World Health Organization to ensure safety environments.
Postmortem Study of Cause of Death Among Children Hospitalized With Respiratory Illness in Kenya
Authors: Njuguna Henry N. , Zaki Sherif R. , Roberts Drucilla J. , Rogena Emily A. , Walong Edwin , Fligner Corinne L. , Keating M. Kelly , Gachii Andrew K. , Maleche-Obimbo Elizabeth , Irimu Grace , Mathaiya John , Orata Noelle , Lopokoiyit Rosemarie , Michuki Jackson , Emukule Gideon O. , Onyango Clayton O. , Gikunju Stella , Owuor Collins , Muturi Peter K. , Bunei Milka , Gloria Carvalho Maria , Fields Barry , Mott Joshua A. , Widdowson Marc-Alain , Chaves Sandra S.
Published: May 2021

Background:

In resource-limited settings, acute respiratory infections continue to be the leading cause of death in young children. We conducted postmortem investigations in children <5 years hospitalized with a clinical diagnosis of respiratory disease at Kenya’s largest referral hospital.

Methods:

We collected respiratory and other tissues postmortem to examine pathologic processes using histology, molecular and immunohistochemistry assays. Nasopharyngeal, trachea, bronchi and lung specimens were tested using 21-target respiratory pathogen real-time reverse transcription polymerase chain reaction assays deployed on Taqman Array Cards. Expert panels reviewed all findings to determine causes of death and associated pathogens.

Results:

From 2014 to 2015, we investigated 64 pediatric deaths (median age 7 months). Pneumonia was determined as cause of death in 70% (42/52) of cases where death was associated with an infectious disease process. The main etiologies of pneumonia deaths were respiratory syncytial virus (RSV) (n = 7, 19%), Pneumocystis jirovecii (n = 7, 19%), influenza A (n = 5, 14%) and Streptococcus pneumoniae (n = 5, 14%)—10% of cases had multi-pathogen involvement. Among the other 10 deaths associated with a nonpneumonia infectious process, 4 did not have an etiology assigned, the others were associated with miliary tuberculosis (2), cerebral thrombosis due to HIV (1), Enterobacteriaceae (1), rotavirus (1), and 1 case of respiratory infection with severe hypokalemia associated with RSV.

Conclusions:

In spite of well-established vaccination programs in Kenya, some deaths were still vaccine preventable. Accelerated development of RSV monoclonal antibodies and vaccines, introduction of seasonal influenza vaccination, and maintenance or improved uptake of existing vaccines can contribute to further reductions in childhood mortality.
The Physician Assistant Student Experience: Diversity, Stress, and School Membership
Authors: Frias Dominique , Yuen Cynthia X.
Published: May 2021

Purpose

This article investigates whether students' stress and psychological sense of school membership (PSSM), which influence their ability to navigate the rigors of PA education, vary by their demographic characteristics.

Methods

In 2017, 4050 matriculating and 2718 graduating PA students reported their demographics and feelings of stress. Graduating students also reported their PSSM. Multiple regressions explored whether students' demographics were associated with their stress and PSSM. Stress analyses controlled for student type (ie, matriculating versus graduating).

Results

Female, underrepresented minority (URM), and graduating students reported more stress when compared to male, non-URM, and matriculating students. URM students reported lower PSSM relative to non-URMs.

Conclusion

URM students' experiences from entering a profession that is predominantly non-Hispanic White may increase stress and reduce PSSM, possibly contributing to lower educational satisfaction and on-time completion rates identified in previous research.
Cardiac Troponin-T Release After Sport and Differences by Age, Sex, Training Type, Volume, and Intensity: A Critical Review
Authors: Cantinotti Massimiliano , Clerico Aldo , Giordano Raffaele , Assanta Nadia , Franchi Eliana , Koestenberger Martin , Marchese Pietro , Storti Simona , D'Ascenzi Flavio
Published: May 2021

Background:

Postexercise release of cardiac troponin (cTn) is a well-known phenomenon, although the influence of various confounders remains unclear. The aim of this critical review was to analyze the postexercise release of cTn according to age, sex, different types of sport, exercise intensity and duration, and training level.

Data Sources:

A literature search was performed within the National Library of Medicine using the following keywords: cTn, peak, release, and exercise. The search was further refined by adding the keywords athletes, children/adolescents, and sport.

Main Results:

For final analysis, 52 studies were included: 43 adult studies, 4 pediatric studies, and 5 with a mixed population of adults and children. Several studies have investigated the kinetics of cTn response after exercise with different biomarkers. The current evidence suggests that sport intensity and duration have significant effects on postexercise cTn elevation, whereas the influence of the type of sport, age, and sex have been not completely defined yet. Most data were obtained during endurance races, whereas evidence is limited (or almost absent), particularly for mixed sports. Data on young adults and professional athletes are limited. Finally, studies on women are extremely limited, and those for non-White are absent.

Conclusions:

Postexercise release of cTn can be observed both in young and master athletes and usually represents a physiological phenomenon; however, more rarely, it may unmask a subclinical cardiac disease. The influence of different confounders (age, sex, sport type/intensity/duration, and training level) should be better clarified to establish individualized ranges of normality for postexercise cTn elevation.
Management of Adult Patients Supported with Venovenous Extracorporeal Membrane Oxygenation (VV ECMO): Guideline from the Extracorporeal Life Support Organization (ELSO)
Authors: Tonna Joseph E. , Abrams Darryl , Brodie Daniel , Greenwood John C. , RUBIO Mateo-Sidron Jose Alfonso , Usman Asad , Fan Eddy
Published: May 2021

Disclaimer: The use of venovenous extracorporeal membrane oxygenation (VV ECMO) in adults has rapidly increased worldwide. This ELSO guideline is intended to be a practical guide to patient selection, initiation, cannulation, management, and weaning of VV ECMO for adult respiratory failure. This is a consensus document which has been updated from the previous version to provide guidance to the clinician.
Methamphetamine Use, Syphilis, and Specific Online Sex Partner Meeting Venues Are Associated With HIV Status Among Urban Black Gay and Bisexual Men Who Have Sex Men
Authors: Jennings Jacky M. , Wagner Jessica , Tilchin Carla , Schumacher Christina M. , Thornton Nicole , Hamill Matthew M. , Rompalo Anne , Ruhs Sebastian , Rives Sarah , Ghanem Khalil G. , Latkin Carl
Published: May 2021

Background

In the context of increasing syphilis rates, particularly among Black men who have sex men (MSM), the objectives were to determine the associations between methamphetamine (meth) use and syphilis and HIV positivity, and to identify sex partner meeting venues as potential intervention access points among Black MSM in a mid-Atlantic US city.

Methods

This study is an ongoing longitudinal cohort study. Participants were recruited from clinical and nonclinical settings and included sexually active MSM aged 18 to 45 years. The baseline visit included a behavioral survey and testing for syphilis, HIV, gonorrhea, and chlamydia. Logistic regression analyses were used for hypothesis testing.

Results

Among 359 MSM completing baseline, 74.4% (268) Black MSM were included; 31% (84) were aged 24 to 29 years, 43.7% (117) reported unprotected anal intercourse at last sex, and 15.3% (41) reported meth use in the past 3 months. Sixteen percent (43) had syphilis, 46.6% (125) were living with HIV, and 19.0% (51) had gonorrhea and/or chlamydia. Meth use was associated with sexual and drug risk behaviors and HIV, but not syphilis. In adjusted analyses, meth use increased the odds of HIV positivity by 6.43 (95% confidence interval, 2.30–17.98) and syphilis positivity by 2.57 (95% confidence interval, 1.23–5.37). Four online sex partner meeting venues were associated with meth use and HIV, whereas syphilis was associated with one.

Conclusions

Among Black MSM, meth use and syphilis positivity were associated with more than 6-fold and almost 3-fold increased adjusted odds of HIV positivity, respectively. Four specific sex partner meeting venues may be important access points for HIV/sexually transmitted infection and substance use prevention.
Can Diagnostic Codes in Health Care Claims Data Identify Confirmed Chlamydial and Gonococcal Infections? A Retrospective Cohort Study, 2003 to 2017
Authors: Mauk Kerry C. , Torrone Elizabeth A. , Flagg Elaine W.
Published: May 2021

Background

Because most sources of administrative claims data do not contain laboratory result data, researchers rely on diagnosis codes to identify cases of disease. The validity of using diagnosis codes to identify chlamydial and gonococcal infections in administrative claims data remains largely uninvestigated.

Methods

We conducted a retrospective cohort analysis using OptumLabs Data Warehouse, which includes deidentified medical (inpatient and outpatient) claims and laboratory test results. Among males and females aged 15 to 39 years during the period 2003–2017, we identified chlamydia and gonorrhea test results and corresponding diagnosis codes. Using test results as the criterion standard, we calculated the sensitivity and specificity of chlamydia and gonorrhea diagnosis codes to identify laboratory-confirmed infections.

Results

We identified 9.7 million chlamydia and gonorrhea test results among 3.1 million enrollees. Of the 176,241 positive chlamydia test results, only 11,515 had a corresponding diagnosis code, for a sensitivity of 6.5 (95% confidence interval [CI], 6.4–6.7) and a specificity of 99.5 (95% CI, 99.5–99.5). Corresponding diagnosis codes were identified for 8056 of the 31,766 positive gonorrhea test results, for a sensitivity of 25.4 (95% CI, 24.9–25.8) and a specificity of 99.7 (95% CI, 99.7–99.7).

Conclusions

Our findings indicate that using only International Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification diagnosis codes to identify chlamydial and gonococcal infections substantially underestimates the burden of these diseases and inaccurately classifies laboratory-confirmed infections.