bluuebunny/crossref_metadata_2025 huggingface dataset:
The biomarker macrophage migration inhibitory factor as a predictor of no-reflow phenomenon and other adverse events in patients with ST-segment elevation myocardial infarction
Authors: Vishnevskaya I , Kopytsya M P , Storozhenko T Y E
Published: October 2021

Major adverse cardiovascular events (MACE) in patients with ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) may be caused by the “no-reflow” phenomenon. Biomarkers for the “no-reflow” phenomenon prediction is being actively studied. Proinflammatory cytokine macrophage migration inhibitory factor (MIF) is one of the promising biomarkers.

Purpose

To estimate the role of MIF in the prediction of early reperfusion myocardial injury and MACE in patients with STEMI.

Methods

The study involved 341 STEMI patients (78.6% male and 21.4% female) with an average age of 59.08±9.65 years. Control group of 12 healthy volunteers included. All patients were made to undergo a baseline investigation. In addition, the level of MIF and soluble suppression of tumorigenicity-2 (sST2) determined twice during the first 12 hours of STEMI, before the PCI and 24 hours after the procedure. Coronary blood flow evaluated using TIMI flow grade and myocardial blush grade (MBG). All patients had epicardial blood flow TIMI 3. The criteria for “no-reflow” diagnosis were myocardial perfusion at MBG 0 or MBG 1 level with complete recovery of epicardial blood flow or ST-segment resolution (rST) of less than 70% from baseline within 2 hours after PCI. All patients were divided into two groups according to MBG and rST after PCI more and less than 70%: 147 patients in the first group with MBG stage 0–1, 182 patients with MBG stage 2–3.

Results

The level of MIF biomarker determined before PCI was significantly higher in the group of patients with MBG 0–1 in comparison to MBG 2–3. (4386,750±676 pg/ml vs 2935±350 pg/ml; p=0,05). Also, the level of sST2, left ventricular mass index and blood glucose were significantly higher in the group of MBG 0–1 (p=0.03, p=0.006 and p=0.0085, respectively). The difference in left ventricle posterior wall thickness and early to late diastolic transmitral flow velocity (p=0.045) was found between two groups. In the group of MBG 0–1 and rST<70% these parameters were significantly lower (p=0,04 and p=0,05, respectively).

Using the multivariate regression analysis, the dependency of the biomarker MIF on the parameters of the reperfusion myocardial injuries were obtained. MIF measured before revascularization was an independent predictor of MBG 0–1 and rST less than 70% (coefficients Beta 0,00057; odd ratio 1,0; 95%confidential interval (CI) 1,0–1,001; p=0,038). The Kaplan-Meier survival analysis showed that long-term adverse outcomes rate after STEMI was significantly higher in patient with the level of MIF determined during the first 12 hours after the event more than 2988 pg/ml (Log-rank = −4,891, p=0.014).

Conclusions

Biomarkers MIF has a capacity as predictive tool for MACE and “no-reflow” phenomenon in STEMI patients.

Funding Acknowledgement

Type of funding sources: None.
Lifelong dietary omega-3 fatty acid reverses cardiac and vascular dysfunction via MMP-2 modulation in aged mice
Authors: Saeedi Saravi S S , Bonetti N R , Vukolic A , Liberale L , Vdovenko D , Luscher T F , Camici G G , Beer J H
Published: October 2021

Background

Aging has a remarkable effect on the cardiovascular system, and negatively causes structural and functional changes in the heart including diastolic/systolic dysfunction and left ventricular (LV) dyssynchrony, as well as, arterial stiffness which may develop to heart failure with preserved ejection fraction (HFpEF) in aged adults. We recently showed that the plant-derived omega-3-fatty-acid α-linolenic-acid (ALA) has emerged to confer potential protective effects against cardiovascular disease. Since cardiovascular aging is a chronic process, we hypothesized that a lifelong effective dietary supplementation with ALA will reverse or prevent age-related diastolic and arterial dysfunction during aging.

Purpose

Here, we test the hypotheses that (1) lifelong dietary ALA will prevent LV diastolic and arterial dysfunction in aged mice and that (2) lifelong dietary ALA will prevent the age-related cardiovascular dysfunction through modiulation of matrix-metalloproteinase-2 (MMP-2) in the heart and arteries.

Methods and results

6-month-old (young) wild-type C57BL/6J mice were fed a low (0.03%), as control, or high ALA (7.3%) diet for more than 12 months. Our results show that aged (>18 months) mice on low ALA diet recapitulate major hallmarks of HFpEF, including diastolic dysfunction with preserved left ventricular ejection fraction, cardiac interstitial fibrosis, impaired acetylcholine-induced relaxation of aortic segments, and arterial stiffness. Intriguingly, we revealed that lifelong ALA-rich diet prevents diastolic dysfunction, vascular relaxation capacity, reduced pulse wave velocity, interstitial fibrosis, and coincident hemodynamic abnormalities in aged mice. Lifelong dietary ALA-in the prevention strategy-was associated with remarkably reduced cardiac and aortic MMP-2 and COX-2 expression, lower levels of pro-inflammatory cytokine TNF-α, and increased isocitrate dehydrogenase 2 (Idh2) expression, decreased function of which has previously been associated with cardiac dysfunction.

Conclusions

Our data support that lifelong ALA-rich diet restores normal cardiac and vascular function in aged mice with LV diastolic and arterial dysfunction and prevents development of age-related cardiovascular dysfunction through the modulation of MMP-2 signaling.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): 1. Swiss National Science Foundation (number 324730_182328)2. the Kardio Stiftung, Baden, Switzerland
A pro-resolving phenotype underpins the anti-inflammatory effects of inorganic nitrate
Authors: Primus C , Masucci M , Whitear C , Montalvo Moreira S A , Ajit Kumar N , Chhetri I , Rathod K S , Khambata R , Kapil V , Ahluwalia A
Published: October 2021

Introduction

Increasing evidence highlights the critical role of chronic inflammation in cardiovascular disease (CVD). Targeting inflammatory pathways in patients with CVD has been associated with improved CV function in pre-clinical (Gee, 2017), early clinical (Yndestad, 2006; Velmurugan 2013; Jones, 2016) and large phase III studies (Ridker, 2017).

The resolution of inflammation is an active process and its failure has also been proposed to contribute to CVD progression. At least one mechanism thought to underlie this failure is dysfunction of the canonical pathway for anti-inflammatory nitric oxide (NO) production. Restoring NO through provision of inorganic nitrate (NO3-) and subsequent bioactivation via the non-canonical pathway may offer therapeutic benefit.

Aim

To test whether dietary NO3–derived NO accelerates resolution of inflammation.

Methods

Randomised, double-blind, placebo-controlled, parallel limb study of 8–10mmol dietary NO3- supplementation versus NO3–deplete placebo beetroot juice in 36 healthy male volunteers (NCT03183830). Using a cantharadin-induced skin blister model (Day, 2001), acute (24h) and chronic (72h)-phase blisters were harvested pre- and post-treatment. Blister exudate was analysed for leucocyte activation state (CD11b, CD62L, CD162) by flow cytometry and cytokine/chemokine composition by ELISA. Ozone chemiluminescence established NO3-/NO2- levels in key biological matrices: plasma, urine and saliva.

Results

9.3mmol inorganic NO3- led to a significant rise (versus placebo, p<0.001) of NO3-/NO2- in plasma, saliva and urine NO2- (p<0.02). No differences were seen in blister volumes, cell counts or markers of systemic inflammation. Whilst no differences were seen in the proportions of cellular infiltrate in 24h blisters, there were significant reductions of neutrophil (p=0.017) and intermediate monocyte proportions (p=0.001) and cellular adhesion molecules across inflammatory, intermediate and resolving monocytes at 72h (Figure 1). Generally, no differences in blister cytokine/chemokine profile was evident except for borderline significant suppression of TNFα at 24hrs with dietary NO3- treatment (P=0.057).

Conclusion

Whilst dietary inorganic NO3- does not impair the essential host defence response it does accelerate resolution: enhanced pro- to anti-inflammatory monocyte subtype switching and curtailed neutrophil recruitment, likely via attenuated TNFα production. These actions offer a novel, easy to administer, approach to influence inflammatory responses without impairing host defence.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Derek Willoughby Trust and British Heart Foundation
The endothelial-enriched lncRNA LINC01235 regulates hypoxia response via HIF-3a
Authors: Gimbel A , Koziarek S , Pham T P , Dimmeler S , Maegdefessel L , Boon R A
Published: October 2021

Background

Cardiovascular diseases (CVDs) remain the leading cause of death worldwide. Hypoxia induces significant changes in cardiovascular control mechanisms potentially resulting in pathophysiology. Recently, an increasing number of long non-coding RNAs (lncRNAs) was reported to participate in the regulation of Hypoxia-inducible factors (HIF). Analysis of single-cell RNA-sequencing of human Abdominal Aortic Aneurysms pinpointed the endothelial-enriched lncRNA LINC01235. LINC01235 was previously correlated with tumour progression in gastric cancer and worse patient prognosis in breast cancer. Globally, the role of LINC01235 in the cardiovascular system remains unknown.

Purpose

The objective of this study is to unravel the function of LINC01235 in endothelial cells (ECs).

Methods and results

LINC01235 levels were elevated in human umbilical vein ECs (7.66 fold, p<0.05), human aortic ECs (16.84 fold, p<0.05) and human dermal microvascular ECs (639.73 fold, p<0.05) over other human cardiovascular cells like vascular smooth muscle cells, aortic fibroblasts and cardiomyocytes. Severe hypoxia (0.2% O2 for 24h) reduced LINC01235 expression significantly (0.33 fold, p<0.05). SiRNA-mediated LINC01235 silencing in HUVECs (0.12, p<0.05) resulted in decreased proliferation (0.76 fold, p<0.05) and vascular endothelial growth factor A (VEGFA)-stimulated angiogenic sprouting (0.39 fold, p<0.05). Loss of LINC01235 did not affect apoptosis, metabolism or barrier function. Analysis of RNA-sequencing data revealed that many hypoxia-responsive genes were downregulated after knockdown of LINC01235 (siCtrl vs. siLINC01235). These included HIF-3α (0.24 fold, p<5.86e-28) as a potential key regulator of the cellular feedback to hypoxia. Phenotypically, knockdown of HIF3A using siRNAs (0.07 fold, p<0.05) resulted in decreased proliferation (0.82 fold, p<0.05) and VEGFA-stimulated angiogenic sprouting (0.50 fold, p<0.05). Accordingly, hypoxia response and LINC01235 knockdown exhibit a negative correlation based on transcriptomics data (R=−0.157, p<2.2e-16), further emphasizing a role of LINC01235 in hypoxia response.

Conclusion

In summary, the EC-enriched lncRNA LINC01235 is likely required for the suppression of hypoxia-induced gene expression under normoxic conditions potentially mediated by HIF-3α. Functionally, loss of LINC01235 decreased proliferation and VEGFA-stimulated angiogenic sprouting without an effect on cell death, metabolism or barrier integrity.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): DFG - TRR267
Platelet-specific deletion of acetyl-CoA carboxylase 1 decreases phospholipid content and impairs platelet functions
Authors: Octave M , Pirotton L , Ginion A , Robaux V , Lepropre S , Kautbally S , Senis Y , Nagy Z , Ambroise J , Guigas B , Giera M , Bertrand L , Beauloye C , Horman S
Published: October 2021

Background

Acetyl-CoA carboxylase (ACC), the first enzyme regulating lipid synthesis, promotes thrombus formation by increasing platelet phospholipid content and thromboxane A2 generation.

Purpose

Our study sought to evaluate whether ACC1 platelet-specific deletion may affect platelet functions by decreasing phospholipid content.

Methods

We generated a new Cre transgenic mouse strain that allows megakaryocyte/platelet specific ACC1 deletion (GpIbCre+/− x ACC1 flx/flx mouse). In vitro, platelet functions were assessed by aggregometry and flow cytometry. In vivo, hemostasis was assessed via the measurement of bleeding time. Lipidomics analysis was carried out on the commercial Lipidyzer platform. Thromboxane A2 secretion was evaluated by ELISA.

Results

As expected, ACC1 deletion was restricted to the megakaryocytic lineage. Hematological parameters in platelet-specific ACC1 knockout mice showed a decrease in platelet count by 30% and an increase in platelet volume by 31%, compared to ACC1 flx/flx platelets. In vitro, platelets from platelet-specific ACC1 knockout mice displayed a decrease in thrombin and CRP-induced platelet aggregation, associated with impaired dense granules secretion. In contrast, ADP-induced platelet aggregation was higher in the absence of ACC1. In vivo, platelet-specific ACC1 knockout mice showed a normal bleeding time. In agreement with our hypothesis, lipidomics analyses showed that ACC1 deletion in platelets was associated with a significant decrease in arachidonic acid-contaning phosphatidylethanolamine plasmalogen, and subsequently with a reduced production of thromboxane A2 upon thrombin or CRP stimulation.

Conclusion

Platelet-specific ACC1 deletion led to a decrease in phospholipid content which, in turn, decreased platelet thromboxane A2 generation, dense granules secretion and aggregation upon thrombin and CRP, but not ADP stimulation. Further studies are needed to elucidate the impact of ADP on platelet functions

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): Fonds pour la formation à la Recherche dans l'Industrie et l'Agriculture (FRIA)
Chromosome-Level Genome Assembly of Nephotettix cincticeps (Uhler, 1896) (Hemiptera: Cicadellidae: Deltocephalinae)
Authors: Yan Bin , Yu Xiaofei , Dai Renhuai , Li Zizhong , Yang Maofa
Published: October 2021

The green rice leafhopper, Nephotettix cincticeps (Uhler), is an important rice pest and a vector of the rice dwarf virus in Asia. Here, we produced a high-quality chromosome-level genome assembly of 753.23 Mb using PacBio (∼110×) and Hi-C data (∼94×). It contained 163 scaffolds and 950 contigs, whose scaffold/contig N50 lengths reached 85.36/2.57 Mb. And 731.19 Mb (97.07%) of the assembly was anchored into eight pseudochromosomes. Genome completeness was attained to 97.0% according to the insect reference Benchmarking Universal Single-Copy Orthologs (BUSCO) gene set (n = 1,367). We masked 347.10 Mb (46.08%) of the genome as repetitive elements. Nine hundred sixty-two noncoding RNAs were identified and 14,337 protein-coding genes were predicted. We also assigned GO term and KEGG pathway annotations for 10,049 and 9,251 genes, respectively. Significantly expanded gene families were primarily involved in immunity, cuticle, digestion, detoxification, and embryonic development. This study provided a crucial genomic resource for better understanding on the biology and evolution in family Cicadellidae.
IPIP27A cooperates with OCRL to support endocytic traffic in the zebrafish pronephric tubule
Authors: Oltrabella Francesca , Jackson-Crawford Anthony , Yan Guanhua , Rixham Sarah , Starborg Tobias , Lowe Martin
Published: October 2021

Endocytosis is a fundamentally important process through which material is internalized into cells from the extracellular environment. In the renal proximal tubule, endocytosis of the abundant scavenger receptor megalin and its co-receptor cubilin play a vital role in retrieving low molecular weight proteins from the renal filtrate. Although we know much about megalin and its ligands, the machinery and mechanisms by which the receptor is trafficked through the endosomal system remain poorly defined. In this study, we show that inositol phosphatase interacting protein of 27 kDa (Ipip27A), an interacting partner of the Lowe syndrome protein oculocerebrorenal syndrome of Lowe (OCRL), is required for endocytic traffic of megalin within the proximal renal tubule of zebrafish larvae. Knockout of Ipip27A phenocopies the endocytic phenotype seen upon loss of OCRL, with a deficit in uptake of both fluid-phase and protein cargo, which is accompanied by a reduction in megalin abundance and altered endosome morphology. Rescue and co-depletion experiments indicate that Ipip27A functions together with OCRL to support proximal tubule endocytosis. The results therefore identify Ipip27A as a new player in endocytic traffic in the proximal tubule in vivo and support the view that defective endocytosis underlies the renal tubulopathy in Lowe syndrome and Dent-2 disease.
¿A quién le pertenece el Sistema Interamericano? Llamado a nuevas perspectivas sociojurídicas en la investigación académicaTo whom does the Inter-american System belong? A call for new socio-legal perspectives
Authors: Huneeus Alexandra
Published: October 2021

Over the past decade, scholarship on the Inter-American System of Human Rights has moved beyond the tradition of doctrinal scholarship to examine the political dynamics of the Inter-American System. Through this line of inquiry, we have gained insights into issues of compliance, resistance and backlash, as well as the dynamics of judicial dialogue and cross-court influence. But there is a blind spot in scholarship on the Inter-American Human Rights system, and it is hindering our ability to understand its evolution in the 21st century. This brief essay is a call for more studies with a socio-legal sensibility, with a hat tip to those who have already begun to inquire in this direction. It is time to focus not only on state actors but also on civil society, and not only on the organs of the Inter-American System of Human Rights as institutional actors, but also the individual actors within those institutions.
Ensuring medication safety for consumers from ethnic minority backgrounds: The need to address unconscious bias within health systems
Authors: Chauhan Ashfaq , Walpola Ramesh Lahiru
Published: October 2021

Medication safety remains a pertinent issue for health systems internationally, with patients from ethnic minority backgrounds recognized at increased risk of exposure to harm resulting from unsafe medication practices. While language and communication barriers remain a central issue for medication safety for patients from ethnic minority backgrounds, increasing evidence suggests that unconscious bias can alter practitioner behaviours, attitudes and decision-making leading to unsafe medication practices for this population. Systemwide, service and individual level approaches such as cultural competency training and self-reflections are used to address this issue, however, the effectiveness of these strategies is not known. While engagement is proposed to improve patient safety, the strategies currently used to address unconscious bias seem tokenistic. We propose that including consumers from ethnic minority backgrounds in design and delivery of the education programs for health professionals, allocating extra time to understand their needs and preferences in care, and co-designing engagement strategies to improve medication related harm with diverse ethnic minority groups are key to mitigating medication related harm arising as a result of unconscious bias.
Mathematical model of the cost-effectiveness of the BioFire FilmArray Blood Culture Identification (BCID) Panel molecular rapid diagnostic test compared with conventional methods for identification of Escherichia coli bloodstream infections
Authors: Mponponsuo Kwadwo , Leal Jenine , Spackman Eldon , Somayaji Ranjani , Gregson Daniel , Rennert-May Elissa
Published: October 2021

Background

Gram-negative pathogens, such as Escherichia coli, are common causes of bloodstream infections (BSIs) and increasingly demonstrate antimicrobial resistance. Molecular rapid diagnostic tests (mRDTs) offer faster pathogen identification and susceptibility results, but higher costs compared with conventional methods. We determined the cost-effectiveness of the BioFire FilmArray Blood Culture Identification (BCID) Panel, as a type of mRDT, compared with conventional methods in the identification of E. coli BSIs.

Methods

We constructed a decision analytic model comparing BCID with conventional methods in the identification and susceptibility testing of hospitalized patients with E. coli BSIs from the perspective of the public healthcare payer. Model inputs were obtained from published literature. Cost-effectiveness was calculated by determining the per-patient admission cost, the QALYs garnered and the incremental cost-effectiveness ratios (ICERs) where applicable. Monte Carlo probabilistic sensitivity analyses and one-way sensitivity analyses were conducted to assess the robustness of the model. All costs reflect 2019 Canadian dollars.

Results

The Monte Carlo probabilistic analyses resulted in cost savings ($27 070.83 versus $35 649.81) and improved QALYs (8.65 versus 7.10) in favour of BCID. At a willingness to pay up to $100 000, BCID had a 72.6%–83.8% chance of being cost-effective. One-way sensitivity analyses revealed length of stay and cost per day of hospitalization to have the most substantial impact on costs and QALYs.

Conclusions

BCID was found to be cost-saving when used to diagnose E. coli BSI compared with conventional testing. Cost savings were most influenced by length of stay and cost per day of hospitalization.
Bias in variance component estimation in swine crossbreeding schemes using selective genotyping and phenotyping strategies
Authors: See Garrett M , Mote Benny E , Spangler Matthew L
Published: October 2021

Selective genotyping of crossbred (CB) animals to include in traditionally purebred (PB) dominated genetic evaluations has been shown to provide an increase in the response to selection for CB performance. However, the inclusion of phenotypes from selectively genotyped CB animals, without the phenotypes of their non-genotyped cohorts, could cause bias in estimated variance components (VC) and subsequent estimated breeding values (EBV). The objective of the study was to determine the impact of selective CB genotyping on VC estimates and subsequent bias in EBV when non-genotyped CB animals are not included in genetic evaluations. A swine crossbreeding scheme producing 3-way CB animals was simulated to create selectively genotyped datasets. The breeding scheme consisted of three PB breeds each with 25 males and 450 females, F1 crosses with 1200 females and 12,000 CB progeny. Eighteen chromosomes each with 100 QTL and 4k SNP markers were simulated. Both PB and CB performance were considered to be moderately heritable (h2=0.4). Factors evaluated were, 1) CB phenotype and genotype inclusion of 15% (n=1800) or 35% (n=4200), 2) genetic correlation between PB and CB performance (rpc=0.1, 0.5 or 0.7) and 3) selective genotyping strategy. Genotyping strategies included: a) Random: random CB selection, b) Top: highest CB phenotype and c) Extreme: half highest and half lowest CB phenotypes. Top and Extreme selective genotyping strategies were considered by selecting animals in full-sib (FS) families or among the CB population (T). In each generation, 4320 PB selection candidates contributed phenotypic and genotypic records. Each scenario was replicated 15 times. VC were estimated for PB and CB performance utilizing bivariate models using pedigree relationships with dams of CB animals considered to be unknown. Estimated values of VC for PB performance were not statistically different from true values. Top selective genotyping strategies produced deflated estimates of phenotypic VC for CB performance compared to true values. When using estimated VC, Top_T and Extreme_T produced the most biased EBV, yet EBV of PB selection candidates for CB performance were most accurate when using Extreme_T. Results suggest that randomly selecting CB animals to genotype or selectively genotyping Top or Extreme CB animals within full-sib families can lead to accurate estimates of additive genetic VC for CB performance and unbiased EBV.
Access-to-Care and Conscience: Conflicting or Coherent?
Authors: Gamble Joel L , Gamble Nathan K
Published: October 2021

“Intervention” is not synonymous with “care.” For an intervention to constitute care—which patients should have a right to access—it must be technically feasible and licit. Now these criteria do not prove sufficient; numerous archaic interventions remain feasible and legally permissible, yet are now bywords for spurious care. Therefore, we propound another necessary condition for an intervention to become care: the physician must rationally judge the intervention to be conducive to the patient’s good. Consequently, the right of access-to-care relies on physicians being free to practice medicine in accord with their consciences, conscience being the rational faculty with which they judge the reasonableness of even mundane medical decisions. Since physicians operate as part of a community, it is further necessary to consider when central bodies may reasonably compel physicians to engage in interventions that the physician believes are not consistent with the patient’s good and/or are not congruent with the purposes of medicine.
A case of pancreatic pseudocyst as a rare cause of a cystic lesion within the psoas muscle
Authors: Doole Emily
Published: October 2021

Acute pancreatitis is highly prevalent in Australia (Nesvaderani et al. Acute pancreatitis: update on management. Med J Aust 2015;202:420–3). Pancreatic pseudocysts, although typically occurring in the peripancreatic tissues, can in up to 25% be extra-pancreatic (Rasch et al. Management of pancreatic pseudocysts—a retrospective analysis. PLoS One 2017;12:e0184374). Extension of pseudocysts into the psoas muscle is highly unusual, with only 13 previously recorded cases (Gupta et al. Retroperitoneal cystic malignant fibromas mimicking a psoas abscess. Iran J Radiol 2015;12:e17507). This article presents the case of a 45-year-old man presenting with progressive left hip pain. He was known to have a history of chronic alcohol misuse. He presented with symptoms and signs typical of psoas pathology and was found to have a large pancreatic pseudocyst extending into his left psoas muscle. In this case, management was via both computed tomography guided percutaneous drainage and endoscopic ultrasound guided drainage. Because of the rarity of psoas pseudocysts and their propensity to mimic other pathology, diagnosis can be extremely challenging. Cystic lesions within the psoas muscle have several differentials, ranging from the more common psoas abscess to extremely rare neoplastic lesions.
Tick-borne encephalitis among US travellers, 2010–20
Authors: Hills Susan L , Broussard Kelly R , Broyhill James C , Shastry Lalita G , Cossaboom Caitlin M , White Jennifer L , Machesky Kimberly D , Kosoy Olga , Girone Kyle , Klena John D , Backenson Bryon P , Gould Carolyn V , Lind Leah , Hieronimus Arielle , Gaines David N , Wong Susan J , Choi Mary J , Laven Janeen J , Staples J Erin , Fischer Marc
Published: October 2021

Background

Tick-borne encephalitis (TBE) is an arboviral disease that is focally endemic in parts of Europe and Asia. TBE cases among US travellers are rare, with previous reports of only six cases among civilian travellers through 2009 and nine military-related cases through 2020. A TBE vaccine was licenced in the USA in August 2021. Understanding TBE epidemiology and risks among US travellers can help with the counselling of travellers going to TBE-endemic areas.

Methods

Diagnostic testing for TBE in the USA is typically performed at the Centers for Disease Control and Prevention (CDC) because no commercial testing is available. Diagnostic testing for TBE at CDC since 2010 was reviewed. For individuals with evidence of TBE virus infection, information was gathered on demographics, clinical presentations and risk factors for infection.

Results

From 2010–20, six patients with TBE were identified. Cases occurred among both paediatric and adult travellers and all were male. Patients were diagnosed with meningitis (n = 2) or encephalitis (n = 4); none died. Cases had travelled to various countries in Europe or Russia. Three cases reported visiting friends or relatives. Activities reported included hiking, camping, trail running, or working outdoors, and two cases had a recognized tick bite.

Conclusions

TBE cases among US travellers are uncommon, with these six cases being the only known TBE cases among civilian travellers during this 11-year period. Nonetheless, given potential disease severity, pre-travel counselling for travellers to TBE-endemic areas should include information on measures to reduce the risk for TBE and other tick-borne diseases, including possible TBE vaccine use if a traveller’s itinerary puts them at higher risk for infection. Clinicians should consider the diagnosis of TBE in a patient with a neurologic or febrile illness recently returned from a TBE-endemic country, particularly if a tick bite or possible tick exposure is reported.
Commission of Human Rights Second Session
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the Working Group on Convention of Human Rights (CHR) Meeting Summary, 10 December 1947.
Commission on Human Rights Second SessionSummary Record
of Thirty-Sixth Meeting
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the CHR Meeting Summary, 13 December 1947.
Commission on Human Rights Second SessionProposal For a
Declaration of Human Rights Submitted by the Representative of the
United States on the Commission on Human Rights
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the Drafting Committee (CHR) United States proposal, 26 November 1947.
Commission on Human Rights Drafting Committee Second
Session
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the Drafting Committee (CHR) Meeting Summary, 6 May 1948.
Commission on Human Rights
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the CHR Recapitulation of amendments, 24 May 1949.
Commission on Human Rights
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the CHR United Kingdom amendment, 1 June 1949.
Commission on Human Rights
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the CHR Meeting Summary, 24 April 1950.
Commission on Human Rights
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the CHR General Adequacy of the First Eighteen Articles, 2 April 1951.
Commission on Human Rights
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the CHR United States amendment, 19 May 1952.
Commission on Human Rights
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the CHR United Kingdom amendment, 19 May 1952.
Commission on Human Rights
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the CHR France amendment, 19 May 1952.
Commission on Human Rights
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the CHR Meeting Summary, 5 June 1952.
Commission on Human Rights
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the CHR United States amendment, 6 June 1952.
Agenda Item 58
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the Third Committee (GA) Meeting Summary, 1 November 1954.
Agenda Item 34
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the Third Committee (GA) Meeting Summary, 19 November 1959.
Fourteenth sessionThird CommitteeAgenda item 34
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the Third Committee (GA) Afghanistan amendment, 9 November 1959.
Fourteenth sessionThird CommitteeAgenda item 34
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the Third Committee (GA) Italy amendment, 19 November 1959.
Agenda Item 34
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the Third Committee (GA) Meeting Summary, 26 November 1959.
Agenda Item 34
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the Third Committee (GA) Meeting Summary, 3 December 1959.
Fourteenth sessionThird CommitteeAgenda item 34
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the Third Committee (GA) Rapporteur suggestions, 1 December 1959.
Principles
Authors: Andrews Neil
Published: October 2021

In this chapter six major principles are identified: freedom of contract; objectivity; the contractual bond principle (‘pacta sunt servanda’); estoppel; good faith and fair dealing; the compensation principle. The nature of each principle is explained and its operation within the law is illustrated and amplified. The first three of these principles are well-established, but it is of particular interest that the good faith principle is recognized here. The principle is manifested in various ways, which are identified. The estoppel principle is a long-standing but complex feature of English private law and its various forms are here explained. The compensation principle encapsulates the complex rules governing the award of damages for breach of contract. The aim of contractual damages is not to punish, nor to over-compensate, or award double compensation. The paradigm award of contractual damages is to place the innocent party in the position which would have existed if there had not been a breach.
Agreement
Authors: Andrews Neil
Published: October 2021

This is a detailed treatment of the rules governing the formation of contract. All facets of that process are covered. Modern ;transactions are often formed by electronic negotiation. Accordingly, the postal rule needs to be supplemented by reference to e-mailed offers and acceptances. Other features of formation include: relief when negotiations abort, based on the principle of unjust enrichment; ‘multipartite contracts’, that is, agreements involving more than two parties; the revocation of offers before acceptance; the special nature of acceptance when the contract is unilateral, rather than both parties having obligations; the possibility of acceptance without words, that is, by conduct; the problem of silence on the part of the offeree; and competition between parties to win the so-called battle of the forms.
Formality
Authors: Andrews Neil
Published: October 2021

The main formalities concern the making of deed or covenants in order to give effect to gratuitous promises (the deed is formalized by the covenantor’s signature, and attestation by a witness to the signature, and delivery of the deed to the covenantee, who need not be present at the time the instrument is executed). Contracts concerning land also need to satisfy the formality of a writing. Although the tendency of English law has been to retreat from formality, various statutory exceptions are examined, notably contracts of guarantee. English law has recognized a ‘no oral modification’ clause, which requires any variation to comply with the prescribed written formality.
Third Parties and Co-Parties
Authors: Andrews Neil
Published: October 2021

An agreement to confer a benefit on a third party is not actionable by the third party at Common Law. Statute has now intervened to modify the position: (i) a direct right of action can be expressly conferred on a named or identifiable third party; (ii) the contract can create by implication such a right, exercisable by a third party, if the contract `purports to confer a benefit’ on such a person. The statute has been examined in the courts and some subtleties have emerged. Claims by parties on behalf of third parties are also considered in this chapter. There is the distinct context in which a promise is made to more than one party, who are known as co-promisees. These technical rules are examined.
Assignment and Agency
Authors: Andrews Neil
Published: October 2021

Assignment is the transfer of the right to sue for a debt or other promised benefit. Assignment has three effects (here, A is the promisor, B is the promisee, and C is the assignee): (i) A, once notified, is obliged to pay C; (ii) C can sue A directly, without joining B as a party to the claim; (iii) A’s obligation to B is discharged if, pursuant to a valid assignment by B to C, A pays C in full. By contrast, if, after B’s assignment of the right to C, A instead pays B, this payment is ineffective to discharge A’s newly transferred obligation towards C. Agency is the process by which an agreement can be formed by X acting on behalf of Y, the latter being the principal. The rules on this topic are complex. This is a succinct account of these rules.
Exclusion Clauses and Consumer Protection
Authors: Andrews Neil
Published: October 2021

An exclusion clause might operate in any of the following three ways: (a) as a limitation clause, imposing a financial cap on the compensation to be paid upon breach; or (b) it might provide for total exclusion of liability for breach; or (c) the clause might constitute a time restriction (an agreed time bar), which requires a claim to be made within a specified period of the alleged harm, that period being shorter than the ordinary limitation period prescribed by statute (ordinarily, six years for breach of contract, twelve years if the action is based on a deed). By a combination of judicial doctrine and (predominantly) statutory regulation, exclusion clauses have become more closely controlled since the Second World War. This chapter explains these responses to this problem.
Applications to Wind up Companies
Authors: French Derek
Published: October 2021

This book deals with a detailed statement of the law on applications to wind up companies in England and Wales in specific and other territories in general. This fourth edition is intended to the procedure for obtaining a winding-up order chronologically from presentation of a petition to making the order. It looks at the application processes which are applied to various classes of petitioners, such as creditors, contributories (shareholders) and public officials. This edition is completely updated to cover new legislation and procedures. It includes new coverage of the Insolvency (England and Wales) Rules 2016, which rewrote the procedural rules for applications to wind up companies. The book also covers Regulation (EU) 2015/848 on insolvency proceedings (recast) concerning amended rules applying to jurisdiction, as well as the special measures then in force to deal with the coronavirus pandemic. Though focused on the procedure in the courts of England and Wales, the work also considers the jurisprudence of the many Commonwealth jurisdictions which have adopted the English procedure. This work contains all there is to know about applying (petitioning) to have companies and similar entities wound up by the court, making it essential for all lawyers who make, or defend, such applications. It states the special measures to deal with the coronavirus pandemic as those measures will appear as necessary in near future.
Growth and dissipation of Be star discs in misaligned binary systems
Authors: Suffak M , Jones C E , Carciofi A C
Published: October 2021

We use a three-dimensional smoothed particle hydrodynamics code to simulate growth and dissipation of Be star discs in systems where the binary orbit is misaligned with respect to the spin axis of the primary star. We investigate six different scenarios of varying orbital period and misalignment angle, feeding the disc at a constant rate for 100 orbital periods, and then letting the disc dissipate for 100 orbital periods. During the disc growth phase, we find that the binary companion tilts the disc away from its initial plane at the equator of the primary star before settling to a constant orientation after 40–50 orbital periods. While the mass-injection into the disc is ongoing, the tilting of the disc can cause material to reaccrete on to the primary star prematurely. Once disc dissipation begins, usually the disc precesses about the binary companion’s orbital axis with precession periods ranging from 20 to 50 orbital periods. In special cases, we detect phenomena of disc tearing, as well as Kozai–Lidov oscillations of the disc. These oscillations reach a maximum eccentricity of about 0.6, and a minimum inclination of about 20○ with respect to the binary’s orbit. We also find the disc material to have highly eccentric orbits beyond the transition radius, where the disc changes from being dominated by viscous forces, to heavily controlled by the companion star, in contrast to its nearly circular motion inwards of the transition radius. Finally, we offer predictions to how these changes will affect Be star observables.
BRAD V3.0: an upgraded Brassicaceae database
Authors: Chen Haixu , Wang Tianpeng , He Xiaoning , Cai Xu , Lin Runmao , Liang Jianli , Wu Jian , King Graham , Wang Xiaowu
Published: October 2021

The Brassicaceae Database (BRAD version 3.0, BRAD V3.0; http://brassicadb.cn) has evolved from the former Brassica Database (BRAD V2.0), and represents an important community portal hosting genome information for multiple Brassica and related Brassicaceae plant species. Since the last update in 2015, the complex genomes of numerous Brassicaceae species have been decoded, accompanied by many omics datasets. To provide an up-to-date service, we report here a major upgrade of the portal. The Model-View-ViewModel (MVVM) framework of BRAD has been re-engineered to enable easy and sustainable maintenance of the database. The collection of genomes has been increased to 26 species, along with optimization of the user interface. Features of the previous version have been retained, with additional new tools for exploring syntenic genes, gene expression and variation data. In the ‘Syntenic Gene @ Subgenome’ module, we added features to view the sequence alignment and phylogenetic relationships of syntenic genes. New modules include ‘MicroSynteny’ for viewing synteny of selected fragment pairs, and ‘Polymorph’ for retrieval of variation data. The updated BRAD provides a substantial expansion of genomic data and a comprehensive improvement of the service available to the Brassicaceae research community.
Extent of resection in glioblastoma: a 10-year local survival analysis
Authors: Hirst Theodore , McAleavey Patrick , Flannery Tom
Published: October 2021

Aims

The impact on extent of resection (EOR) in glioblastoma has been well documented. It is clear that gross-total resection (GTR) confers best overall survival (OS), however the minimum EOR required to confer a survival benefit over biopsy is debated. Recent studies favour partial resection (PR) over biopsy for IDH-wildtype, MGMT-unmethylated tumours. We describe our experiences locally with these principles in mind.

Method

Retrospective evaluation of a single surgeon cohort. All patients over 18 years old, undergoing a surgical treatment for histologically confirmed GBM in the stated period were included. We collected information on demographics, tumour volume, EOR, complications, adjuvant therapies, molecular profile, and OS. We used log rank tests and Cox Proportional Hazards Models to identify factors associated with OS.

Results

The patient and tumour characteristics of our cohort were similar to those documented in the literature. The mean age was 56.6 years. 72 patients underwent biopsy and 202 had debulking surgery. Median OS was 11 months. Of those debulked, gross-total resection was achieved in 41 patients (20%); associated median OS was 29 months. Patients receiving partial resection (defined as EOR <80%) had no clear survival benefit over patients undergoing biopsy (median OS 6 vs 5 months) but had a higher rate of post-op neurological deficit (3% vs 12%). Tumour molecular profile appeared to influence survival outcome in a manner comparable to worldwide experience.

Conclusion

In our experience, partial resection is not a justifiable surgical aim in the typical glioblastoma cohort. The limited benefit that it may confer over biopsy appears to be outweighed by the risk of neurological deficit that affects quality and probably quantity of life. This finding applies to our glioblastoma population in general as well as those specifically with an MGM-unmethylated tumour.
The impact of the COVID-19 pandemic on paediatric glioma patients in low, middle, and high-income countries: a multicentre, international, observational cohort study
Authors: Bandyopadhyay Soham ,   Dr. Global Children’s NCDs Collaborative
Published: October 2021

Aims

Paediatric cancer is a leading cause of non-communicable disease deaths for children worldwide, with more than 90% of deaths occurring in low-and-middle-income countries (LMICs). The COVID-19 pandemic may have exacerbated disparities in paediatric cancer outcomes between LMICs and HICs. The World Health Organization (WHO) Global Initiative for Childhood Cancer has identified gliomas as a common cancer that can act as a benchmark for assessing global paediatric cancer care. This study aims to ascertain the short and medium-term outcome across 17 countries during the COVID-19 pandemic by determining 30- and 90-day all-cause mortality rates for paediatric glioma patients who underwent treatment.

Method

A multicentre, international, mixed- (retrospective and prospective), collaborative cohort study in 17 countries. Patients were recruited between March 12th 2020 and July 12th 2020.

Results

129 patients were recruited with the majority being histologically diagnosed as low-grade gliomas (n = 86/118, 72.9%). Seven children had a change to their planned chemotherapy treatment because of the COVID-19 pandemic. Similarly, seven children and eleven children had a change to their planned radiotherapy treatment and surgical treatment respectively because of the COVID-19 pandemic. Five patients died within the 30-day follow-up period, with all five patients being in LMICs. A sixth child, also in a LMIC, died within the 90-day follow-up period. This significant difference in mortality between LMICs and HICs was present when controlling for confounding for factors such as grade, ASA status, sex, weight, and age.

Conclusion

There has been relatively minimal change to the treatment of paediatric gliomas worldwide compared to their initial planned care. There was a significant difference in mortality for childhood gliomas between LMICS and high-income countries during the COVID-19 pandemic. There needs to be a concerted effort to improve equity in health outcomes globally.