bluuebunny/crossref_metadata_2025 huggingface dataset:
P596 Trough concentration of ustekinumab was a useful biomarker for the prediction of treatment-effects in patients with Crohn’s Diseases
Authors: Kato S , Yamaga N , Ishibashi A , Kani K , Yakabi K , Nagoshi S
Published: May 2021

Background

Ustekinumab, anti-IL12/23 antibody have contributed to the good prognosis in patients with Crohn’s disease (CD). However, good biomarkers for the prediction of treatment- effects of ustekinumab (UST) are not clear. We elucidated whether trough concentration of UST could predict the clinical remission and seronegative inflammation in CD patients in clinical practice.

Methods

This was a single-centre prospective observational study approved by the institutional review board of our hospital. Forty CD patients treated by administration of intravenous UST 6 mg/kg and subcutaneous UST 90mg every 8 weeks were enrolled in this study. CDAI, serum CRP and plasma UST trough concentration were evaluated at every visit. All data were examined in total patients, patients with UST induction at remission state after pretreatment (Induction at remission group) and patients with UST induction at active state after pretreatment (Induction at non-remission group). Endpoints were time course changes of clinical remission rate, CDAI, CRP and UST trough concentration until week 40.

Results

In total, 40 participants were included in the final analysis. The mean age and disease duration of the participants were 41.3 and 11.7 years. Of the participants, 65% (26/40) were male, 25% (10/40) used thiopurine, and 30% (12/40) used steroids. TNF-failure of the patients were 65.0% (26/40). Remission rate of total patients significantly increased at week 8 (30, 60, 68, 78, 78, and 73% at every 8 weeks from baseline). Both CDAI and CRP significantly decreased from baseline at week 8. Remission rate of Induction at remission group (n=12) did not significantly decrease from baseline (100, 92, 92, 92, 92, and 83% at every 8 weeks from baseline). Remission rate of Induction at non-remission group (n=28) significantly increased until week 24 from baseline (0, 46, 57, 71, 71, and 68% at every 8 weeks from baseline). Trough concentrations of total patients at week 8, 16, 24 were 3.54, 1.57 and 1.43 μg/mL, respectively. Trough at each week was not significantly different between Induction at remission and at non-remission groups. Immunomodulator use did not affect trough concentration. Cut-off values of prediction for remission at week 8, 16, and 24 were 2.80, 1.28* and 1.12* μg/mL, respectively. Cut-off values of prediction for normal CRP at week 8, 16, and 24 were 3.27, 1.24* and 1.24* mg/mL, respectively (*: Each factor significantly could be detected).

Conclusion

UST trough concentration at subcutaneous injection could predict clinical remission and normal CRP. Pretreatment did not affect UST trough concentration.
P618 Treatment outcomes of patients with Crohn’s disease and complex perianal fistula in five European countries: the PREFACE retrospective study
Authors: Ferrante M , Siproudhis L , Poggioli G , Reinshagen M , Milicevic S , Roset M , Bent-Ennakhi N , D’Ambrosio R , Fernandez-Nistal A , Panes J
Published: May 2021

Background

Presence of fistulas in Crohn’s disease (CD) is an indicator of poor prognosis; 20% of CD patients suffer from perianal fistula. There are few studies specifically designed to assess treatment outcomes in complex perianal fistula (CPF) in CD. This retrospective chart review study describes the outcomes of patients with CPF in CD in five European countries after medical and/or surgical treatment.

Methods

Adult patients with CD receiving treatment for a new episode of CPF during the eligibility period (September 2011 to September 2014), in Belgium, France, Germany, Italy and Spain, were included. Index date was defined as date of any medical or surgical CPF treatment initiation. Data was collected from CD diagnosis to at least 3 years after index date (except for deceased or lost to follow-up patients) to describe patient characteristics and treatments used for all CPF episodes since CD diagnosis. Effectiveness outcomes were measured as remission rates based on Fistula Drainage Assessment (FDA) recorded in medical charts for fistula reported at index date (index fistula). Remission rates are expressed as percentage rates on patient level after 6- and 12-months follow-up period. For calculation of treatment outcomes, the most recent FDA prior to the respective timepoint was used.

Results

A total of 372 patients (51% male) with a mean (SD) age of 38 (13) were included by 31 sites. Median time since CD diagnosis was 7 years, and median length of follow-up was 6 years. A total of 498 CPFs were presented at index date and during FU period. Out of the 498 CPFs, 94% were treated with at least one surgical intervention (most frequent: 61% long-term seton placement, 51% surgical drainage) and 82% with at least one medical treatment (most frequent: 40% anti-TNFs, 33% antibiotics, 16% immunosuppressants). After 6 months the remission rate at patient level for index fistula was 28% and after 12 months 35%.

Conclusion

Current standards of care achieved remission in one third of patients with CPF in CD over a period of one year. Improved therapeutic strategies and new treatment options are required to improve outcomes in this manifestation of CD.
P627 Change in urgency among ulcerative colitis patients: Analyses from the SPARC IBD
Authors: Lewis J , Shan M , Xhou X , Naegeli A , Hunter T
Published: May 2021

Background

The objective of this study was to assess the changes in prevalence and severity of fecal urgency in Ulcerative Colitis (UC) patients at 6-months from their enrollment visit.

Methods

Data from patients in the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD) were analyzed. UC patients that had an enrollment visit and 6-month visit were included in these analyses. Fecal urgency at each visit was assessed on a scale ranging from 0 (none) to 4 (severe). The change in urgency status from enrollment visit to 6-months is categorized as Improvement (decrease of 1–3 points), No Change, or Worsening (increase of 1–3 points). Descriptive statistics and contingency tables were created to summarize baseline characteristics by fecal urgency group. Chi-square tests, Fisher’s exact tests, ANOVA and Wilcoxon rank sum tests were conducted to compare the distribution of baseline characteristics between change in urgency groups, with Bonferroni corrections used for multiple comparisons.

Results

Data from 272 UC patients were included in this analysis. 25% of UC patients had an improvement in urgency, 54.4% had no change, 20.6% had a worsening of urgency at 6-months from their enrollment visit.

When compared to patients that had no change in urgency at 6-months, UC patients that had improvement in urgency were more likely to have a higher baseline UCDAI (p<0.0001), mean daily bowel movements (p<0.0001), mean daily liquid bowel movements (P<0.0001), elevated stool frequency relative to their normal when well (p<0.0001), liquid stool consistency (p=0.0418), blood in stools (p=0.0001), abdominal pain (p=0.0065), moderate/severe fecal urgency (p<0.0001), worse general well-being (p<0.0001), moderate/severe Physician Global Assessment (PGA) (p=0.0013), and steroid use (p=0.0287) (Table 1). When compared to patients with worsening urgency at 6-months, UC patients that had an improvement in urgency at 6-months were more likely to have a higher baseline UCDAI (p<0.0001), mean daily bowel movements (p<0.0001), mean daily liquid bowel movement (P<0.0001), more stool frequency relative to their normal when well (p<0.0001), moderate/severe fecal urgency (p<0.0001), worse general well-being (p=0.0053), and moderate/severe PGA (p=0.0022). There were no statistically significant differences in baseline characteristics between UC patients that had a worsening or no change in urgency at 6-months.

Conclusion

Fecal urgency is a common symptom among UC patients. Urgency is not a stable symptom, with nearly 50% experiencing either worsening or improvement over 6-months. Worse disease activity at enrollment in the cohort was associated with improved fecal urgency symptoms over 6-months.
P684 Multiplex Gastrointestinal Pathogen Panel Testing is Associated with Higher Rates of Inflammatory Bowel Disease Therapy Escalation in Patients Hospitalised with Flare
Authors: Verma A , Axelrad J
Published: May 2021

Background

Although the role of Clostridioides difficile infection (CDI) testing in inflammatory bowel disease (IBD) flare is well established, the function of additionally testing for non-CDI enteric infections (EI) via multiplex gastrointestinal pathogen polymerase chain reaction (GI panel) stool tests remains unclear. Patients with PCR-confirmed EI are less likely to have IBD therapy escalated; however, it is unknown whether performing testing itself affects IBD-related decision-making and outcomes. This is vital given the similar clinical presentations of flare and EI. We examined differences in IBD outcomes among patients who – in addition to testing for CDI – were and were not co-tested for EI during hospitalisation for flare.

Methods

We conducted a retrospective cohort study of IBD patients hospitalised with flare and tested for CDI at an urban academic medical centre. We collected data on demographics, IBD disease severity, IBD therapy, and antibiotic therapy. Patients were cohorted by co-testing for EI using a GI panel. The primary outcome was escalation of IBD therapy within 24 hours of emergency department presentation. Each IBD therapy was also studied separately. Secondary outcomes were antibiotic therapy, length of stay, and colectomy.

Results

Of 134 patients, 66 (49.3%) were co-tested and 7 (10.6%) had an EI detected. Disease severity and CDI rates were comparable between groups (Table 1). Co-tested patients were more likely to receive a new IBD therapy (92.4% vs. 75.0%, p=0.006), specifically intravenous (IV) steroids (89.4% vs. 36.8%, p=<0.001; Table 2). Patients who were not co-tested were more likely to have their existing IBD therapy continued on admission. Co-tested patients were less likely to undergo colonoscopy during admission and had lower rates of prolonged antibiotic therapy (>10 days; 4.5% vs. 14.7%, p=0.047), although prolonged antibiotic use was comparable between groups after excluding patients treated for CDI (5.1% co-tested vs. 1.8% not co-tested, p=0.276). Colectomy rates and length of stay were comparable between groups.

Conclusion

Co-testing for non-CDI enteric pathogens by GI panel was associated with a greater degree of inpatient IBD flare management – especially IV steroids. Patients not co-tested were more likely to stay on their existing IBD therapy regimen despite similar flare severities at presentation. Given the low pathogen detection rates, early negative testing for EI may promote provider confidence in intensifying IBD therapy. Early clinical improvement after therapy escalation may obviate the need for colonoscopy in these patients. Use of the GI panel may affect IBD decision-making during relapse, and should be considered in all IBD patients hospitalised with flare.
Ultrasound-guided genicular nerves block: an analgesic alternative to local infiltration analgesia for total knee arthroplasty
Authors: Pietrantoni Pierangela , Cuñat Tomás , Nuevo-Gayoso Montserrat , Martín Nuria , Tió Montserrat , Basora Misericordia , Sastre Sergi , Sala-Blanch Xavier
Published: May 2021

BACKGROUND

Standard analgesic strategies for total knee arthroplasty employ local infiltration analgesia. Blockade and radiofrequency ablation of the genicular nerves are effective treatments for patients with chronic pain because of knee osteoarthritis.

OBJECTIVE

To test the noninferiority of the analgesic effect of genicular nerves block in comparison with local infiltration analgesia after 24 h of total knee arthroplasty.

DESIGN

Prospective cohort study.

SETTING

Perioperative setting.

PATIENTS

Thirty-five patients scheduled for total knee arthroplasty were prospectively included in the study and compared with 35 patients in a retrospective cohort.

INTERVENTION

Genicular nerve blocks in the prospective cohort were compared with local infiltration analgesia in the retrospective cohort.

MAIN OUTCOME MEASURES

The pain numeric rating scale and the cumulative opioid consumption in oral morphine equivalents during the first 24 h.

RESULTS

We conducted propensity score-matched analyses of patients using acute postoperative pain-related risk covariates. After one-to-one propensity score matching, 21 patients were included in the local infiltration analgesia group and 21 in the genicular nerve block group. The median difference in numeric rating score at rest at 24 h was −0.99 [95% confidence interval (CI), −1.99 to 0.5, P = 0.012] on the unmatched cohort and −1.9 (95% CI, −2 to 0, P = 0.002) on the matched cohort (meeting the noninferiority criteria, Δ=1). The median difference in cumulative opioid consumption was 2.5 mg (95% CI, −13.5 to 2.5, P < 0.001) for the unmatched cohort and 4.99 mg (95% CI, −11.5 to 2.5, P < 0.001) on the matched group (meeting the noninferiority criteria, Δ = 21 mg).

CONCLUSION

Local infiltration analgesia and genicular nerve block are comparable in terms of analgesic results. Therefore, genicular nerves block is an alternative to local infiltration analgesia in patients undergoing total knee arthroplasty.

TRIAL REGISTRATION

Clinicaltrials.gov identifier: NCT04024319.
Trends in combat casualty care following the publication of clinical practice guidelines
Authors: Nadler Roy , Tsur Avishai M. , Lipsky Ari M. , Benov Avi , Sorkin Alex , Glassberg Elon , Chen Jacob
Published: May 2021

BACKGROUND

The current study explores the trends in the application of combat casualty care following the publication of clinical practice guidelines (CPGs) in five domains for 13 years.

METHODS

The Israel Defense Forces Trauma Registry was used to assess practice and adherence to guidelines in five domains: (a) crystalloid transfusions, (b) tranexamic acid use, (c) freeze-dried plasma use, (d) chest decompression, and (e) airway management. All patients injured between January 2006 and December 2018 were included in the analysis. Trends were analyzed and presented monthly using linear regression and were compared using the Chow test.

RESULTS

The mean ± SD crystalloid volume transfused decreased from 1,179 ± 653 mL in 2006 to 466 ± 202 mL in 2018 (B = 0.016, 0.006–0.044). The proportion of patients with an indication treated with tranexamic acid dropped from 8% (238 of 2,979 patients) to 2.5% (60 of 2,356 patients) following the stricter guideline's publication. Freeze-dried plasma administration in indicated casualties rose from 12.5% in 2013 to 48% in 2018 (B = 1.63, 1.3–2.05). The overall proportion of casualties undergoing chest decompression rose from 1% (61 of 6,036 casualties) to 1.5% (155 of 10,493 casualties) following the release of a new CPG in 2012 (p = 0.013). There were no significant trends in intubation ratios before (B = 0.987, 0.953–1.02) or after 2012 (B = 10.2, 0.996–1.05).

CONCLUSION

Some aspects demonstrate the desired trends in response to new CPGs; in others, initial improvement is achieved but followed by stagnation. In some medical care aspects, completely unexpected and undesirable trends are observed. Every change and update in CPGs should be based on reliable data. The effect of every change must be monitored carefully to ensure adequate adherence to lifesaving guidelines.

LEVEL OF EVIDENCE

Epidemiological study, level IV.
Safety and efficacy of low-titer O whole blood resuscitation in a civilian level I trauma center
Authors: Kemp Bohan Phillip M. , McCarthy Patrick M. , Wall Morgan E. , Adams Alexandra M. , Chick Robert C. , Forcum Jason E. , Radowsky Jason S. , How Remealle A. , Sams Valerie G.
Published: May 2021

BACKGROUND

Military experience has shown low-titer O whole blood (LTOWB) to be safe and beneficial in the resuscitation of hemorrhaging trauma patients. However, few civilian centers use LTOWB for trauma resuscitation. We evaluated the early experience and safety of a LTOWB program at a level 1 civilian trauma center.

METHODS

We retrospectively reviewed our trauma registry from January 2018 to June 2020 for patients admitted in shock (defined as ≥1 of the following: heart rate, >120 beats per minute; systolic blood pressure, <90 mm Hg; or shock index, >0.9) who received blood products within 24 hours. Patients were grouped by resuscitation provided: LTOWB (group 1), component therapy (CT; group 2), and LTOWB-CT (group 3). Safety, outcomes, and variables associated with LTOWB transfusion and mortality were analyzed.

RESULTS

216 patients were included: 34 in Group 1, 95 in Group 2, and 87 in Group 3. Patientsreceiving LTOWB were more commonly male (p<0.001) and had a penetrating injury (p=0.005). Groups 1 and 3 had higher median ISS scores compared to Group 2 (19 and 20 vs 17; p=0.01). Group 3 received more median units of blood product in the first 4h (p<0.001) and in the first 24h (p<0.001). There was no difference between groups in 24h mortality or transfusion-related complications (all p>0.05). Arrival ED SBP was associated with LTOWB transfusion (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.95-1.00, p=0.03). ED lactate was independently associated with 24h mortality. (OR 1.27, CI 1.02-1.58, p=0.03). LTOWB transfusion was not associated with mortality (p=0.49). Abstract.

CONCLUSION

Severely injured patients received LTOWB-CT and more overall product units but had similar 24 h mortality when compared with the LTOWB or CT groups. No increase in transfusion-related complications was seen after LTOWB transfusion. Low-titer O whole blood should be strongly considered in the resuscitation of trauma patients at civilian centers.

LEVEL OF EVIDENCE

Retrospective, therapeutic, level IV.
Inequity in discharge pain management for trauma patients with limited English proficiency
Authors: Schwartz Hope E.M. , Matthay Zachary A. , Menza Rebecca , Fernández Alicia , Mackersie Robert , Stein Deborah M. , Bongiovanni Tasce
Published: May 2021

INTRODUCTION

Pain management is critical for optimal recovery after trauma. Previous work at our institution revealed differences in pain assessment by patient language, which may impact management. This study aimed to understand differences in discharge opioid prescribing for trauma patients with limited English proficiency (LEP).

METHODS

We conducted a cross-sectional study of adult trauma patients discharged to the community from a diverse, urban level 1 trauma center in 2018. Opioid prescriptions were obtained from discharge pharmacy records and converted to standard oral morphine equivalents (OMEs). Multivariable logistic and quantile regression was used to examine the relationship between LEP, opioid prescriptions, and OMEs at discharge, controlling for demographic and clinical characteristics.

RESULTS

Of 1,419 patients included in this study, 83% were English proficient (EP) and 17% were LEP. At discharge, 56% of EP patients received an opioid prescription, compared with 41% of LEP patients. In multivariable models, EP patients were 1.63 times more likely to receive any opioid prescription (95% CI, 1.17–2.25; p = 0.003). Mean OME was 147 for EP and 94 for LEP patients. In multivariable models, the difference between EP and LEP patients was 40 OMEs (95% CI, 21.10–84.22; p = 0.004). In adjusted quantile regression models, differences in total OMEs increased with the amount of OMEs prescribed. There was no difference in OMEs at the 20th and 40th percentile of total OMEs, but LEP patients received 26 fewer OMEs on average at the 60th percentile (95% CI, −3.23 to 54.90; p = 0.081) and 45 fewer OMEs at the 80th percentile (95% CI, 5.48–84.48; p = 0.026).

CONCLUSION

Limited English proficiency patients with traumatic injuries were less likely to receive any opioid prescription and were prescribed lower quantities of opiates, which could contribute to suboptimal pain management and recovery. Addressing these disparities is an important focus for future quality improvement efforts.

LEVEL OF EVIDENCE

Care Management, level IV.
Predeployment training of Army medics assigned to prehospital settings
Authors: Suresh Mithun R. , Valdez-Delgado Krystal K. , Staudt Amanda M. , Trevino Jennifer D. , Papalski Wayne N. , Greydanus Dominique J. , Twilligear Kaleb J. , Mann-Salinas Elizabeth A. , VanFosson Christopher A.
Published: May 2021

BACKGROUND

Medics have numerous responsibilities in the combat theater, which include performing lifesaving interventions, providing basic medical and nursing care, and caring for casualties in a variety of scenarios unique to the battlefield. An evaluation of the medic predeployment training paradigm is important and will help to understand its current state and identify areas for improvement. Therefore, the purpose of this study was to perform a focused assessment of Army medic predeployment training to identify patterns that might inform future medic training.

METHODS

A web-based survey was created using the Intelink.gov platform and sent by e-mail to Army medics who deployed since 2001. Medics were asked to reflect upon the predeployment training from their most recent deployment experience. There were multiple choice, Likert-type scale, and free-text response questions. Descriptive statistics were used to analyze the results.

RESULTS

There were 254 respondents who met the study inclusion criteria. Most of the respondents had their clinical competency evaluated (68.5%, n = 174). Respondents reported several acute trauma, basic nursing, and battlefield medicine skills as being critical but also felt that many of these same skills would have benefited from additional predeployment training. Most of the respondents felt very or fully confident and prepared to provide combat casualty care (74.8%, n = 190 and 74.8%, n = 190). There were 64 respondents (25.2%) who reported feeling not at all, slightly, or moderately confident, and 54 (84.4%) of these respondents described in a free-text question wanting additional training before deployment.

CONCLUSION

Respondents reported many skills as being critical to combat casualty care, but several of these skills would have benefited from additional predeployment training. Respondents with more deployment experience or completion of more predeployment training reported feeling more confident and prepared to provide combat casualty care. A common sentiment was the desire for more training of any form before deployment.

LEVEL OF EVIDENCE

Epidemiological, level IV.
Role of albumin on endothelial basement membrane and hemostasis in a rat model of hemorrhagic shock
Authors: Torres Luciana N. , Salgado Christi L. , Dubick Michael A. , Cap Andrew P. , Torres Filho Ivo P.
Published: May 2021

BACKGROUND

We sought to determine the extent of loss of endothelial basement membrane (BM), leukocyte recruitment, and changes in coagulation after hemorrhagic shock, followed by limited-volume resuscitation (LVR) with 5% albumin (ALB).

METHODS

Anesthetized rats were bled 40% of blood volume and assigned to treatment groups: untreated (n = 6), LVR with normal saline (NS; n = 8), or LVR with ALB (n = 8). Sham rats (n = 6) underwent all procedures except hemorrhage or resuscitation. Blood samples were assayed for active proteases, such as metalloproteinase 9 (MMP-9) and a disintegrin and metalloproteinase 10 (ADAM-10), BM-type heparan sulfate proteoglycan (perlecan), cell count, and coagulation function. Leukocyte transmigration was used to estimate the net efficiency of leukocyte recruitment in cremaster venules.

RESULTS

Hemorrhage significantly lowered red cell count, but white cell and platelet counts did not change (vs. sham). Ionized calcium in plasma was significantly reduced in untreated and remained so after NS. In contrast, ionized calcium was normalized after ALB. Plasma expansion after NS and ALB further reduced leukocyte and platelet counts. Metalloproteinase 9, ADAM-10, and perlecan were significantly higher in untreated rats (vs. sham). Albumin normalized MMP-9, ADAM-10, and perlecan levels, while NS further increased MMP-9, ADAM-10, and perlecan (vs. sham). Transmigrated leukocytes doubled in the untreated group and remained elevated after NS (vs. sham) but normalized after ALB. Albumin reduced every stage of the leukocyte recruitment process to sham levels.

CONCLUSION

Despite similar plasma expansion, NS weakened platelet function contrary to ALB. Plasma expansion with ALB resulted in restoration of BM integrity and attenuation of leukocyte recruitment to tissues, in contrast to NS. Albumin plays a critical role in restoring BM integrity, attenuating leukocyte recruitment to tissues, and optimizing hemostasis by increasing ionized calcium in plasma.
Measuring the exposure of primate reservoir hosts to mosquito vectors in Malaysian Borneo
Authors: Brown Rebecca , Salgado-Lynn Milena , Jumail Amaziasizamoria , Jalius Cyrlen , Chua Tock-Hing , Vythilingam Indra , Ferguson Heather M.
Published: May 2021

Several vector-borne pathogens of primates have potential for human spillover. An example is the simian malaria Plasmodium knowlesi which is now a major public health problem in Malaysia. Characterization of exposure to mosquito vectors is essential for assessment of the force of infection within wild primate populations, however few methods exist to do so. Here we demonstrate the use of thermal imaging and Mosquito Magnet Independence Traps (MMIT) to assess the abundance, diversity and infection rates in mosquitoes host seeking near long-tailed macaque (Macaca fasicularis) sleeping sites in the Lower Kinabatangan Wildlife Sanctuary, Malaysian Borneo. The primary Plasmodium knowlesi vector, Anopheles balabacensis, was trapped at higher abundance near sleeping sites than control trees. Although none of the An. balabacensis collected (n=15) were positive for P. knowlesi, two were infected with another primate malaria Plasmodium inui. Analysis of macaque stools from sleeping sites confirmed a high prevalence of Plasmodium infection, suspected to be P. inui. Plasmodium inui infections have not yet been reported in humans, but its presence in An. balabacensis here and previously in human-biting collections highlight its potential for spillover. We advocate the use of MMITs for non-invasive sampling of mosquito vectors that host seek on wild primate populations.
Capturing Global, Predicting Local for Controlling Antimicrobial Resistance: a retrospective multivariable analysis
Authors: Awasthi Raghav , Rakholia Vaidehi , Agarwal Samprati , Dhingra Lovedeep Singh , Nagori Aditya , Sethi Tavpritesh
Published: May 2021

Background

Antimicrobial resistance (AMR) is a complex multifactorial outcome of health, socio-economic and geopolitical factors. Therefore, tailored solutions for mitigation strategies could be more effective in dealing with this challenge. Knowledge-synthesis and actionable models learned upon large datasets are critical in order to diffuse the risk of entering into a post-antimicrobial era.

Objective

This work is focused on learning Global determinants of AMR and predicting the susceptibility of antibiotics at the isolate level (Local) for WHO (world health organization) declared critically important pathogens Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, Enterobacter cloacae, Staphylococcus aureus.

Methods

In this study, we used longitudinal data (2004-2017) of AMR having 633820 isolates from 70 Middle and High-income countries. We integrated AMR data with the Global burden of disease (GBD), Governance (WGI), and Finance data sets in order to find the unbiased and actionable determinants of AMR. We chose a Bayesian Decision Network (BDN) approach within the causal modeling framework to quantify determinants of AMR. Finally Integrating Bayesian networks with classical machine learning approaches lead to effective modeling of the level of AMR.

Results

From MAR (Multiple Antibiotic Resistance) scores, we found that developing countries are at higher risk of AMR compared to developed countries, for all the critically important pathogens. Also, Principal Components Analysis(PCA) revealed that governance, finance, and disease burden variables have a strong association with AMR. We further quantified the impact of determinants in a probabilistic way and observed that health system access and government effectiveness are strong actionable factors in reducing AMR, which was in turn confirmed by what-if analysis. Finally, our supervised machine learning models have shown decent performance, with the highest on Staphylococcus aureus. For Staphylococcus aureus, our model predicted susceptibility to Ceftaroline and Oxacillin with the highest AUROC, 0.94(with SE of 0.01%) and 0.89(with SE of 0.002%) respectively.
In vitro hepatotoxicity assessment of Lippia javanica (Burm.f.) Spreng. aqueous leaf extract
Authors: Swanepoel Bresler , Koekemoer Trevor C , Venables Luanne , Cloete Elsabe , Khumalo Nonhlanhla P , van de Venter Maryna
Published: May 2021

Ethnopharmacological relevance: Lippia javanica leaves are popular in traditional food, medicine and for insecticidal uses in various Africa countries and North-East India. Anecdotal evidence suggests that it is safe to use but limited animal studies suggested potential toxicity at high dosages, including hepatotoxicity. Aim of the study: To screen for potential hepatotoxicity of L. javanica leaf extracts in vitro, thereby contributing to its toxicological profile for safe use in food and topical applications. Materials and methods: High content analysis techniques and fluorescent dyes were used to monitor C3A hepatocarcinoma cells for changes in morphological features that are associated with development of mitotoxicity, steatosis, oxidative stress, and lysosomal dysfunction. Results: No changes were observed in cell viability, reactive oxygen species or lysosomal content at concentrations up to 200 μg/ml in C3A cells. Mitochondrial membrane potential was reduced by approximately 10% but this effect was not dose-dependent nor was it accompanied by a reduction in mitochondrial content. A dose-dependent decrease was observed in neutral lipid content. Conclusion: The results from this in vitro study suggest that L. javanica leaf extracts is not anticipated to be hepatotoxic at concentrations in the range that is assumed for food or topical use.
Effect of δ-ferrite on susceptibility to hydrogen embrittlement of 304 austenitic stainless steel in high-pressure hydrogen atmosphere
Authors: Bao Fan , Zhang Kaiyu , Zhou Zhengrong , Zhang Wenli , Cai Xiao , Zhang Lin
Published: May 2021

Purpose

The purpose of this paper is to demonstrate the effect of δ-ferrite on the susceptibility to hydrogen embrittlement of type 304 stainless steel in hydrogen gas environment.

Design/methodology/approach

The mechanical properties of as-received and solution-treated specimens were investigated by the test of tensile and fatigue crack growth (FCG) in 5 MPa argon and hydrogen.

Findings

The presence of δ-ferrite reduced the relative elongation and the relative reduction area (H2/Ar) of 304 stainless steel, indicating that δ-ferrite increased the susceptibility of hydrogen embrittlement in 304 stainless steel. Moreover, δ-ferrite promoted the fatigue crack initiation and propagation at the interface between δ-ferrite and austenite. The FCG tests were used to investigate the effect of δ-ferrite on the FCG rate in hydrogen gas environment, and it was found that δ-ferrite accelerated the FCG rate, which was attributed to rapid diffusion and accumulation of hydrogen around the fatigue crack tip through δ-ferrite in high-pressure hydrogen gas environment.

Originality/value

The dependence of the susceptibility to hydrogen embrittlement on δ-ferrite was first investigated in type 304 steel in hydrogen environment with high pressures, which provided the basis for the design and development of a high strength, hydrogen embrittle-resistant austenitic stainless steel.
Differential responses of soil nitrogen‐oxide emissions to organic substitution for synthetic fertilizer and biochar amendment in a subtropical tea plantation
Authors: Han Zhaoqiang , Wang Jinyang , Xu Pinshang , Li Zhutao , Liu Shuwei , Zou Jianwen
Published: May 2021

Tropical and subtropical acidic soils have been well documented as hotspots of global soil nitrogen (N) oxide (i.e., nitrous oxide (N2O) and nitric oxide (NO) emissions). While the effectiveness of possible mitigation options has been extensively examined in croplands, little is known about their effectiveness in reducing N‐oxide emissions from acidic soils of rapidly expanding tea plantations in China. Here, we conducted a 2‐year field experiment to investigate how organic substitution for synthetic fertilizer and biochar amendment affect soil N‐oxide emissions from a subtropical tea plantation. Across the 2‐year measurement period, full organic substitution for synthetic fertilizer significantly increased N2O emissions by an average of 17% while had a lower NO emission compared to synthetic fertilizer alone. Our global meta‐analysis further revealed that full or partial organic fertilizer substitution resulted in a 29% (95% confidence interval: 5%–60%) increase of N2O emissions from acidic soils. In contrast, irrespective of fertilizer type, biochar amendment significantly reduced N2O emissions by 14% in the first but not second experimental year, suggesting a transient effect. The trade‐off effect of full organic substitution on N2O and NO emissions may be attributed to the favorable conditions for N2O production due to the stimulated activity of nitrifiers and denitrifiers. The suppression of N2O emission following biochar amendment was probably due to promoted further reduction of N2O to dinitrogen. The fertilizer‐induced emission factor (EF) of N2O (2.1%) in the tea plantation was greater than the current IPCC default value, but the EF of NO (0.8%) was comparable to the global estimate. Taken together, while biochar amendment could have mitigation potential, cautions are needed when applying organic substitution for synthetic fertilizer as mitigation options for acidic soils as hotspots of N‐oxide emissions.
The effect of ligation methods on biofilm formation in patients undergoing multi‐bracketed fixed orthodontic therapy – A systematic review
Authors: Skilbeck Michael G , Mei Li , Mohammed Hisham , Cannon Richard D , Farella Mauro
Published: May 2021

Background

Many modifications to fixed orthodontic appliances have been introduced to manage biofilm formation. The aim of this review was to investigate elastomeric ligation in comparison with stainless steel ligation and self‐ligation with regard to microbiological and clinical indicators of biofilm formation in patients wearing multi‐bracketed fixed orthodontic appliances.

Methods

The MEDLINE and the EMBASE databases were searched up to February 2021 and supplemented by additional manual searches of bibliographies. Parallel‐group and split‐mouth randomized controlled trials (RCTs) comparing different ligation methods were identified. The Cochrane Risk of Bias‐2 tool was applied to assess the quality of evidence.

Results

A total of 11 RCTs were included in this review. Nine RCTs compared self‐ligation and elastomeric ligation; two compared elastomeric ligation and stainless steel ligation. The included studies had either some concerns or were at a high risk of bias. Qualitative assessment of the studies identified that there were no significant differences in biofilm formation between elastomeric ligation and self‐ligation, but that stainless steel ligation was less susceptible to biofilm formation than elastomeric ligation.

Conclusions

There were no significant differences between self‐ligation and elastomeric ligation for biofilm formation in patients wearing multi‐bracketed fixed orthodontic appliances. Stainless steel ligation may accumulate less biofilm than elastomeric ligation; however, the clinical significance of the difference could not be evaluated. Further high‐quality studies are required in order to determine which ligation method is better for managing biofilm formation in patients wearing multi‐bracketed fixed orthodontic appliances.
ENERGY-EFFICIENT POWER ALLOCATION FOR IMPERFECT CSI DOWNLINK NOMA SYSTEM
Authors: Aldebes Reem , Dimyati Kaharudin , Hanafi Effariza
Published: May 2021

The fifth generation (5G) networks must provide the massively increased number of users by thousand times higher data rate at lower power consumption. Thus, optimizing the energy efficiency (EE) becomes an essential issue that has to be researched from the green communication perspective. Non-orthogonal multiple access (NOMA) is considered one of the high potential techniques in fifth-generation systems. This technology is favorable to maximize the energy efficiency and the spectrum efficiency by composing different signals at the same time on the same carrier at different power levels. In this paper, a low complexity power allocation algorithm is proposed in imperfect channel state information (CSI) downlink NOMA cellular system, where obtaining full CSI at the base station is considered a challenge. The proposed algorithm relies on the fact that the allocated power is inversely proportional to the channel strength of the user to implement the successive interference cancellation (SIC) technique at the user terminal to reconstruct the desired signal. The performance of the system is analyzed in terms of energy efficiency and outage probability and compared to the conventional orthogonal multiple access (OMA) system. Results show that the proposed algorithm increases the energy efficiency by about 50% compared to the conventional OMA technology, and an improvement in the outage probability has been achieved. Furthermore, the effect of the error in the channel estimation on the energy efficiency in imperfect CSI NOMA system is evaluated. The simulation shows that the energy efficiency reduces when the channel estimation error increases; and the best performance is achieved in the perfect CSI case where the channel estimation error is zero.
EXPERIMENTAL INVESTIGATION OF AN ACOUSTIC METAMATERIAL BARRIER DESIGN COMPOSED OF A SQUARE PRISM WITHIN A HEXAGONAL RECESS
Authors: Mu Luo , Zulkefli Zamir Aimaduddin , Abdul Jalil Nawal Aswan , Putra Azma , Othman Muhammad Nur , Raja Ahmad Raja Mohd Kamil
Published: May 2021

This paper presents an experimental investigation of an acoustic barrier composed out of an acousticmetamaterial unit cell. The design of the unit cell consists of a square prism, acting as a resonator,within a hexagonal recess manufactured out of a single material. Two materials were used tomanufacture the unit cell: PolyMide Polycarbonate and Polylite Polylactic Acid. The acousticperformance of the unit cell was quantified for both materials using the acoustic absorptioncoefficient and acoustic transmission loss values for frequencies between 100 Hz and 5,000Hz. Theexperimental results indicate that the design reduced the peak absorption coefficient for bothmaterials while also introducing two additional peaks at around 1,500 Hz and at 4,000 Hz. Changesto the absorption coefficient values were observed for frequencies above 1,000 Hz while minimalchanges were observed for frequencies below 1,000 Hz. These results indicate that the proposeddesign, is able to widen the effective frequency band, or stop band for acoustic absorption forfrequencies above 1,000 Hz compared to the absorption coefficient of the material. The experimentalresults also indicate that the design increases the peak transmission loss by about 7 dB at 4,000 Hz.For sounds below 3,000 Hz, the design will only change the transmission loss by about 3 dB forfrequencies between 100 Hz to 3,000 Hz. These results indicate that the acoustic metamaterial design,consisting of resonator in a recess manufactured out of a single material, is able to broaden theeffective frequency range for sound absorption for frequencies between 1,000 Hz and 4,000 Hz andat increasing the transmission loss values for frequencies between 3,000 Hz and 5,000 Hz. It can beconcluded that the resonator in recess metamaterial design, manufactured out of a single material,can be used to increase the stop band for acoustic absorption for frequencies above 1,000 Hz and toincrease the transmission loss for frequencies above 3,000 Hz.
The Fear Domain of Iban Sebuyau, Sarawak Communities Euphemisms:	Metaphor Conceptual Analysis / Domain Ketakutan Bahasa Halus Masyarakat Iban Sebuyau, Sarawak: Satu Analisis Metafora Konseptual
Authors: Ringit Clinton , Abdul Wahab Hamidah , Gedat Remmy
Published: May 2021

This paper examines the use of subtle language or euphemisms in the fear domain of the Iban Sebuyau community, Sarawak. The data of this qualitative study was obtained through a field study, involving 10 Iban informants who are permanent residents in the district of Sebuyau, aged between 40-70 years. The study informants consisted of five males and five females. Structured interview method was conducted to obtain data from the fear domain, guided by questions related to the element of fear of a concrete and abstract entity. The five data analyzed in this paper are akar kayu’ (wood root), jelu sungkur (shovel animal), aki’ (grandfather), utai terebai (flying object), and bisi’ orang (the presence of people). The Conceptual Metaphor approach from the cognitive semantic framework applied in the data analysis of this study succeeded in unraveling the cognitive relationship based on the knowledge and experience of the speaker with the lexical euphemisms of Iban Sebuyau. This study provides an important contribution to the vocabulary of knowledge, in addition to explain the use of euphemisms in this domain as one of the forms of figurative language that is important and significant in the daily communication of the Iban Sebuyau community
Reviewer Acknowledgements
Authors: Brown Bennett
Published: May 2021

International Journal of Law and Public Administration (IJLPA) would like to acknowledge the following reviewers for their assistance with peer review of manuscripts for this volume. Many authors, regardless of whether IJLPA publishes their work, appreciate the helpful feedback provided by the reviewers. Their comments and suggestions were of great help to the authors in improving the quality of their papers. Each of the reviewers listed below returned at least one review for this volume.Reviewers for Volume 4, Number 1Adrian Cristian Moise, Spiru Haret University of Bucharest, RomaniaAndrea Kajcsa, University of Medicine, RomaniaAntonio Fortes Martín, Carlos III University of Madrid, SpainBranko Dimeski, St. Kliment Ohridski University, MacedoniaDragoljub Popović, Union University School of Law, SerbiaEncarnación Abad Arenas, National University of Distance Education (UNED), SpainIvan Kosnica, University of Zagreb, CroatiaJohn Mark R. Asio, Gordon College, PhilippinesJosé Sebastián Kurlat Aimar, University of Buenos Aires, ArgentinaRose Casimiro, Nueva Ecija University of Science and Technology, PhilippinesTatiana Bachvarova, Special Tribunal for Lebanon, BulgariaTaylisi de Souza Corrêa Leite, Anhanguera University, BrazilThomas Prehi Botchway, University of Education, Winneba, GhanaBennett BrownEditorial AssistantInternational Journal of Law and Public Administration--------------------------------------------------------------------Redfame Publishing9450 SW Gemini Dr. #99416Beaverton, OR 97008, USATel: 1-503-828-0536 ext. 511Fax: 1-503-828-0537E-mail: ijlpa@redfame.comURL: http://ijlpa.redfame.com
Solid-Phase Radioimmunoassay for Detecting Bovine (Neonatal Calf Diarrhea) Rotavirus Antibody
Authors: Babiuk Lorne A. , Acres Stephen D. , Rouse Barry T.
Published: May 2021

An indirect solid-phase microradioimmunoassay is described for detecting antibodies against rotaviruses. The test involved ethanol fixation of microcultures of bovine rotavirus-infected BSC-1 cells and reaction with bovine antirotavirus serum, followed by
125
I-labeled rabbit anti-bovine immunoglobulin G. The technique was shown to be virus specific and highly sensitive. The fixed microcultures could be stored at 4°C for at least 2 months without affecting the sensitivity of the test. The application of this system for the detection of rotavirus antibodies in humans is briefly discussed.
Serum antibody to Pseudomonas aeruginosa exotoxin measured by a passive hemagglutination assay
Authors: Pollack M , Taylor n s
Published: May 2021

A passive hemagglutination (PHA) assay for antibody to Pseudomonas aeruginosa exotoxin is described which utilizes chromic chloride-treated ovine erythrocytes coated with purified toxin. PHA antitoxin titers correlated well with those obtained by a cytotoxicity neutralization assay (r = 0.91, P less than 0.001), whereas the PHA assay was four to eight times as sensitive. The mean serum PHA titer of 16 patients convalescing from recent pseudomonas infections (log2 = 9.4 +/- 3.9) was significantly higher (P less than 0.001) than that of 17 healthy controls (2,7 +/- 2.6), and fourfold or greater rises were demonstrated in 5 of 7 patients examined sequentially. The lower levels of PHA antibody in sera from 11 of 17 controls suggested the acquisition of antitoxin secondary to asymptomatic infection.
Relationship of K1 antigen to biotype in clinical isolates of Escherichia coli
Authors: Myerowitz R L , Albers A C , Yee R B , Orskov F
Published: May 2021

Two hundred and ninety-four isolates of Escherichia coli, including 105 from blood cultures, 94 from stools of hospital inpatients, and 96 from rectal cultures of healthy young adults, were biotyped by using the API-20E system and tested for the presence of K1 antigen. The overall frequency of K1 strains was 14.2% and was similar among the three sources. Forty-eight biotypes were observed, but two-thirds of all isolates, including two-thirds of the K1 strains, belonged to only five biotypes. Among the five commonest biotypes, the distribution of K1 strains was nonrandom, since 23 of the 27 K1 strains belonged to only two biotypes. Analysis of the O and H antigens of K1 strains indicated that this correlation of biotype with K1 antigen was due to a restricted number of serovars ("clones") that were repeatedly isolated from the population studied. These serovas included O18:K1:H7, O1:121:H6 and O16:K1:H6. Although a statistically significant correlation between biotype and K1 antigen was observed, the correlation was not sufficiently great to alow biotyping to be of significant predictive value as a marker for the K1 antigen.
Growth of cell wall-defective variants of Escherichia coli: comparison of aerobic and anaerobic induction frequencies
Authors: Huber T W , Brinkley A W
Published: May 2021

A method for quantitating the conversion of Escherichia coli to colony-forming, cell wall-defective (CWD) bacteria has been developed. The induction frequency, i.e., the percentage of the population recovered as CWD colonies was determined for 20 randomly selected clinical isolates of E. coli under aerobic and anaerobic incubation conditions. Penicillin (1,000 U/ML) was the inducing agent. The 20 strains segregated into three groups. Group I organisms produced CWD colonies with high frequency both aerobically and anaerobically. Grout II organisms showed a much higher induction frequency anaerobically than aerobically. Group III organisms were poor inducers. Thirty percent of the strains were group I, 50% were group II, and 20% were group III organisms. These data indicate that anaerobic conditions enhance the induction and growth of CWD E. coli in the research laboratory and suggest that anaerobic incubation may be important in recovery of medically significant CWD bacteria.