bluuebunny/crossref_metadata_2025 huggingface dataset:
Angled Crested Like Water Waves with Surface Tension II: Zero Surface Tension Limit
Authors: Agrawal Siddhant
Published: January 2024

This is the second paper in a series of papers analyzing angled crested like water waves with surface tension. We consider the 2D capillary gravity water wave equation and assume that the fluid is inviscid, incompressible, irrotational and the air density is zero. In the first paper \cite{Ag19} we constructed a weighted energy which generalizes the energy of Kinsey and Wu \cite{KiWu18} to the case of non-zero surface tension, and proved a local wellposedness result. In this paper we prove that under a suitable scaling regime, the zero surface tension limit of these solutions with surface tension are solutions to the gravity water wave equation which includes waves with angled crests.
Weierstrass bridges
Authors: Schied Alexander , Zhang Zhenyuan
Published: January 2024

We introduce a new class of stochastic processes called fractional Wiener–Weierstraß bridges. They arise by applying the convolution from the construction of the classical, fractal Weierstraß functions to an underlying fractional Brownian bridge. By analyzing the

p
p

-th variation of the fractional Wiener–Weierstraß bridge along the sequence of

b
b

-adic partitions, we identify two regimes in which the processes exhibit distinct sample path properties. We also analyze the critical case between those two regimes for Wiener–Weierstraß bridges that are based on a standard Brownian bridge. We furthermore prove that fractional Wiener–Weierstraß bridges are never semimartingales, and we show that their covariance functions are typically fractal functions. Some of our results are extended to Weierstraß bridges based on bridges derived from a general continuous Gaussian martingale.
The ubiquitin ligases Cbl and Cbl-b regulate macrophage growth by controlling CSF-1R import into macropinosomes
Authors: Huang Lu , Thiex Natalie W. , Lou Jieqiong , Ahmad Gulzar , An Wei , Low-Nam Shalini T. , Kerkvliet Jason G. , Band Hamid , Hoppe Adam D.
Published: January 2024

The ubiquitination of transmembrane receptors regulates endocytosis, intracellular traffic, and signal transduction. Bone marrow−derived macrophages from myeloid Cbl–/– and Cbl-b–/– double knockout (DKO) mice display sustained proliferation mirroring the myeloproliferative disease that these mice succumb to. Here, we found that the ubiquitin ligases Cbl and Cbl-b have overlapping functions for controlling the endocytosis and intracellular traffic of the CSF-1R. DKO macrophages displayed complete loss of ubiquitination of the CSF-1R whereas partial ubiquitination was observed for either single Cbl–/– or Cbl-b–/– macrophages. Unlike wild type, DKO macrophages were immortal and displayed slower CSF-1R internalization, elevated AKT signaling, and a failure to transport the CSF-1R into the lumen of nascent macropinosomes, leaving its cytoplasmic region available for signaling. CSF-1R degradation depended upon lysosomal vATPase activity in both WT and DKO macrophages, with this degradation confined to macropinosomes in WT but occurring in distributed/tubular lysosomes in DKO cells. RNA-sequencing comparison of Cbl–/–, Cbl-b–/– and DKO macrophages indicated that while the overall macrophage transcriptional program remained intact, DKO macrophages had alterations in gene expression associated with growth factor signaling, cell cycle, inflammation and senescence. Cbl-b–/– had minimal effect on the transcriptional program whereas Cbl–/– led to more alternations but only DKO macrophages demonstrated substantial changes in the transcriptome, suggesting overlapping but unique functions for the two Cbl-family members. Thus, Cbl/Cbl-b-mediated ubiquitination of CSF-1R regulates its endocytic fate, constrains inflammatory gene expression, and regulates signaling for macrophage proliferation.
Evolution of REperfusion Strategies and impact on mortality in Old and Very OLD STEMI patients. The RESOVOLD-e-MUST study
Authors: Lapostolle Frédéric , Petrovic Tomislav , Moiteaux Brice , Loyeau Aurélie , Boche Thévy , Kadji Kalabang Roger , Le Bail Gaëlle , Lamhaut Lionel , Lafay Marina , Dupas François , Scannavino Marine , Benamer Hakim , Bataille Sophie , Lambert Yves
Published: January 2024

Background

The use of myocardial reperfusion—mainly via angioplasty—has increased in our region to over 95%. We wondered whether old and very old patients have benefited from this development.

Methods

Setting: Greater Paris Area (Ile-de-France).

Data

Regional registry, prospective, including since 2003, data from 39 mobile intensive care units performing prehospital treatment of patients with ST segment elevation myocardial infarction (STEMI) (<24 h).

Parameters

Demographic, decision to perform reperfusion and outcome (in-hospital mortality).

Primary endpoint

Reperfusion decision rate by decade over age 70.

Secondary endpoint

Outcome.

Results

We analysed the prehospital management of 27,294 patients. There were 21,311 (78%) men and 5,919 (22%) women with a median age of 61 (52–73 years). Among these patients, 8,138 (30%) were > 70 years, 3,784 (14%) > 80 years and 672 (2%) > 90 years.

The reperfusion decision rate was 94%. It decreased significantly with age: 93, 90 and 76% in patients in their seventh, eighth and ninth decade, respectively. The reperfusion decision rate increased significantly over time. It increased in all age groups, especially the higher ones. Mortality was 6%. It increased significantly with age: 8, 16 and 25% in patients in their seventh, eighth and ninth decade, respectively. It significantly decreased over time in all age groups. The odds ratio of the impact of reperfusion decision on mortality reached 0.42 (0.26–0.68) in patients over 90 years.

Conclusion

the increase in the reperfusion decision rate was the greatest in the oldest patients. It reduced mortality even in patients over 90 years of age.
O07 CHILD syndrome and ILVEN: disorders on the same spectrum?
Authors: Paudel Pratima , Salimi Maryam , Igbokwe Rebecca , Taibjee Saleem , Ogboli Malobi , Moss Celia , Ibbs Samantha
Published: January 2024

Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects (CHILD syndrome) is a rare X-linked dominant disorder caused by hemizygous variants in the NSDHL gene. Typically, affected girls are born with unilateral skin lesions in a Blaschkoid distribution due to random X-inactivation, and ipsilateral limb reductions. We report a genetically confirmed case without significant limb reductions and consider the relationship of CHILD syndrome to inflammatory linear verrucous epidermal naevus (ILVEN) also sometimes caused by mosaic variants in NSDHL.

A 9-month-old girl presented with extensive congenital red, scaly lesions in a Blaschkoid distribution confined to the right side of her body. Examination was otherwise normal apart from sensorineural deafness in the right ear and overlapping right 4th and 5th toes. Histology showed the characteristic foamy histiocytes of CHILD syndrome and genetic testing revealed a heterozygous pathogenic variant of NSDHL, c.262C>T p.(Arg88*) previously reported in CHILD syndrome.

Patients clinically diagnosed with ILVEN but with NSDHL mutations have sometimes been reclassified as CHILD syndrome (König A et al. ILVEN encompasses a spectrum of inflammatory mosaic disorders. Am. J.Med.Genet. 2000;90:339-46). The histology of ILVEN is less specific than CHILD syndrome, without the characteristic foamy histiocytes. Nonetheless these conditions could be on a spectrum, with limb defects arising if mutant skin cells overlie the primitive limb bud (Moss C, Burn J. Hypothesis: CHILD+ILVEN=PEN or PENCIL J.Med.Genet. 1990;27:390-391).

NSDHL controls cholesterol synthesis and the topical treatment with statins plus cholesterol effective in CHILD syndrome could be considered in some cases of ILVEN.
O09 Targeted genetic therapy for congenital melanocytic naevi
Authors: Bryant Dale , Barberan-Martin Sara , Maeshima Ruhina , Del Valle Torres Ignacio , Rabii Mohammad , Sauvadet Aimie , Demetriou Charalambos , Knöpfel Nicole , Michailides Fanis , Riachi Melissa , Zecchin Davide , Pittman Alan , Polubothu Satyamaanasa , Hart Steve , Kinsler Veronica
Published: January 2024

Severe cases of congenital melanocytic naevi (CMN) are associated with substantial cutaneous and neurological morbidity and an excess childhood mortality from melanoma. Effective treatments are lacking. This mosaic disorder is caused most commonly by a heterozygous oncogenic variant NRAS c.181C>A, p.(Q61K). As NRAS has multiple downstream effectors we have sought to treat this disease by precision genetic therapy rather than downstream pathway inhibition, hypothesising that silencing of the oncogenic allele may remove cellular protection from RAS induced apoptosis. Using a lead siRNA selected for allele specificity and fewest off-target effects on RNAseq (siNRASQ61K) we show here significant selective knockdown of variant mRNA expression and knockdown of NRAS protein levels. A single treatment to primary naevus cell cultures leads to normalisation of MAPK pathway activation, reduction in proliferation rate, and importantly, triggering of apoptosis. We go on to demonstrate that receptor-targeted lipid nanoparticles (RTNPs) successfully protect siRNA from degradation, deliver cargo to naevus cells in patient skin explants and improve naevus cell targeting. A single intradermal injection of siNRASQ61K-RTNPs into transgenic mice harbouring humanised NRASQ61K(Tyr::NRASQ61K) confirms significant selective knockdown of the variant NRAS allele in vivo.Successful targeting of variant NRAS and triggering of naevus cell apoptosis now paves the way for clinical trials of this genetic therapy for CMN.
P18 Giant Periocular Juvenile Xanthogranulomas Treated with Trametinib
Authors: Poudel Pratima , Millen Gerard , Ogboli Malobi
Published: January 2024

Juvenile Xanthogranuloma (JXG), the commonest type of non-Langerhans cell histiocytosis, is regarded as a benign self-limiting condition of infancy, characterised by asymptomatic yellow brown papulonodular lesions, usually confined to the skin but occasionally affecting the eyes or internal organs. Skin lesions characteristically regress spontaneously within 3-6 years. We describe an unusually aggressive cutaneous presentation requiring input from paediatric oncology.

A 6 year old boy presented with extensive soft yellowish papules, plaques and nodules particularly around the eyes but also over the chest and leg. Biopsy confirmed the clinical diagnosis of JXG. The lesions enlarged progressively with new lesions appearing, causing significant distortion of the upper and lower eyelids with reduced ability to open the eyes, discomfort and distress.

Treatment was started with topical steroids, progressing to intralesional and systemic steroids, but with minimal effect. In view of the severity, vinblastine and subsequently cytarabine were added, again with limited benefit. The periocular lesions were surgically debulked and he was commenced on Trametinib (a MEK inhibitor) with a good response. Now aged 9 years, and the patient displayed a favourable clinical response after 3 months of being on Trametinib.

JXG rarely requires treatment, but there is no recognised therapy for the occasional problematic lesions. In this case trametinib was effective and well-tolerated. The efficacy of trametinib in histiocytosis has been attributed to the presence of activating BRAF and MAP2K1 mutations. Genetic analysis of JXG may guide future therapies.
Adverse healthcare experiences are correlated with increased time to diagnosis in women with vulvar inflammatory dermatoses: a retrospective cohort survey
Authors: Rivera Sydney , Dehner Kylie , Flood Anna , Dykstra Chandler , Mauskar Melissa M , DeMaria Andrea L
Published: January 2024

This retrospective cohort survey of over 300 women examined diagnostic delay in vulvar dermatoses compared with nonvulvar control conditions (e.g. psoriasis or atopic dermatitis). Adverse healthcare experiences (e.g. uncertainty of which provider to consult, embarrassment in talking to providers) occurred more often for participants with vulvar disease and were significantly correlated with increased time to diagnosis in this group, which was not the case in control conditions. The findings suggest opportunities to improve care for people with vulvar disease.
Five paediatric patients with mycosis fungoides and our approach to provide age-appropriate information and psychological support
Authors: Melchionda Veronica , Ieremia Eleni , Matin Rubeta , McPherson Tess
Published: January 2024

Cutaneous lymphoproliferative diseases in childhood are rare and they are clinically and pathologically heterogeneous, which makes their diagnosis challenging. Although there is limited long-term data and guidance on management, evidence suggests these to be different conditions from cutaneous lymphoma in adults, highlighting the need for age-appropriate patient information. We present clinical outcomes for our paediatric cohort of five patients with mycosis fungoides, emphasizing that despite diagnostic delays, mycosis fungoides in this age group tends to yield a good prognosis. It remains uncommon to provide clinical expertise together with psychological support in a dermatology paediatric service. Here, we provide our experience in offering this combined service. In conjunction with these patients, we have co-produced an accessible patient information leaflet targeted at a younger audience for support and to clarify potential misconceptions from a diagnosis of cutaneous lymphoma.
Evaluation of the 2023 Duke-ISCVID and 2023 Duke-ESC Clinical Criteria for the Diagnosis of Infective Endocarditis in a Multicenter Cohort of Patients With Staphylococcus aureus Bacteremia
Authors: Papadimitriou-Olivgeris Matthaios , Monney Pierre , Frank Michelle , Tzimas Georgios , Tozzi Piergiorgio , Kirsch Matthias , Van Hemelrijck Mathias , Bauernschmitt Robert , Epprecht Jana , Guery Benoit , Hasse Barbara
Published: January 2024

Background

The Duke criteria for infective endocarditis (IE) diagnosis underwent revisions in 2023 by the European Society of Cardiology (ESC) and the International Society for Cardiovascular Infectious Diseases (ISCVID). This study aims to assess the diagnostic accuracy of these criteria, focusing on patients with Staphylococcus aureus bacteremia (SAB).

Methods

This Swiss multicenter study conducted between 2014 and 2023 pooled data from three cohorts. It evaluated the performance of each iteration of the Duke criteria by assessing the degree of concordance between definite S. aureus IE (SAIE) and the diagnoses made by the Endocarditis Team (2018–23) or IE expert clinicians (2014–17).

Results

Among 1344 SAB episodes analyzed, 486 (36%) were identified as cases of SAIE. The 2023 Duke-ISCVID and 2023 Duke-ESC criteria demonstrated improved sensitivity for SAIE diagnosis (81% and 82%, respectively) compared to the 2015 Duke-ESC criteria (75%). However, the new criteria exhibited reduced specificity for SAIE (96% for both) compared to the 2015 criteria (99%). Spondylodiscitis was more prevalent among patients with SAIE compared to those with SAB alone (10% vs 7%, P = .026). However, when patients meeting the minor 2015 Duke-ESC vascular criterion were excluded, the incidence of spondylodiscitis was similar between SAIE and SAB patients (6% vs 5%, P = .461).

Conclusions

The 2023 Duke-ISCVID and 2023 Duke-ESC clinical criteria show improved sensitivity for SAIE diagnosis compared to 2015 Duke-ESC criteria. However, this increase in sensitivity comes at the expense of reduced specificity. Future research should aim at evaluating the impact of each component introduced within these criteria.
Deaf patients’ preferred communication in clinical settings: implications for healthcare providers
Authors: Hall Sarah , Ballard Michael
Published: December 2023

Deaf patients who communicate in American Sign Language (ASL) experience communication challenges leading to medical errors, treatment delays, and health disparities. Research on Deaf patient communication preferences is sparse. Researchers conducted focus groups based on the Health Belief Model with culturally Deaf patients and interpreters. The ASL focus groups were interpreted and transcribed into written English, verified by a third-party interpreting agency, and uploaded into NVivo. Deductive coding was used to identify communication methods and inductive coding was used to identify themes within each. Writing back-and-forth introduced challenges related to English proficiency, medical terminology, poor penmanship, and tendencies of providers to abbreviate. Participants had various speechreading abilities and described challenges with mask mandates. Multiple issues were identified with family and friends as proxy interpreters, including a lack of training, confidentiality issues, emotional support, and patient autonomy. Video remote interpreter challenges included technical, environmental, and interpreter qualification concerns. Participants overwhelmingly preferred on-site interpreters for communication clarity. While there was a preference for direct care, many acknowledged this is not always feasible due to lack of providers fluent in ASL. Access to on-site interpreters is vital for many Deaf patients to provide full access to critical medical information. Budget allocation for on-call interpreters is important in emergency settings.
Methionol as an aggregation-sex pheromone of the desert-dwelling beetleEustromula valida(Coleoptera: Cerambycidae)
Authors: Halloran Sean , Zou Yunfan , Arriola Kyle , Roepke René , Hanks Lawrence M , Millar Jocelyn G
Published: December 2023

As part of a long-term project on unraveling the use of pheromones in the large beetle family Cerambycidae, field trials were conducted with generic blends of known cerambycid pheromones at a desert site in southern California. In the first year of testing (2022), the species Eustromula valida (LeConte) (subfamily Cerambycinae, tribe Elaphidiini) and Aethecerinus latecinctus (Horn) (Cerambycinae, Trachyderini) were weakly attracted to one of the lure blends. In follow-up trials in 2023, only E. valida were caught, and collection of volatiles from both sexes of E. valida determined that males sex-specifically produced 3-methylthiopropan-1-ol (methionol), a compound that was not in the tested lure blends. Beetles of both sexes were strongly and specifically attracted to this compound in field bioassays, verifying that it is an aggregation-sex pheromone. No sympatric species were attracted to methionol while it was deployed in the field. Several recent studies have identified methionol as a pheromone component for other cerambycid species in both North and South America, suggesting it may represent another common pheromone component within the Cerambycidae.
Sex differences in the nutritional status and its association with long-term prognosis in patients with heart failure with reduced ejection fraction: a prospective cohort study
Authors: Kałużna-Oleksy Marta , Krysztofiak Helena , Sawczak Filip , Kukfisz Agata , Szczechla Magdalena , Soloch Aleksandra , Cierzniak Maria , Szubarga Alicja , Przytarska Katarzyna , Dudek Magdalena , Uchmanowicz Izabella , Straburzyńska-Migaj Ewa
Published: January 2024

Aims

Many studies show the association between malnutrition and poor prognosis in heart failure (HF) patients. Our research aimed to analyse sex differences in patients with HF with reduced ejection fraction (HFrEF), emphasizing nutritional status and the influence of selected parameters on the prognosis.

Methods and results

We enrolled 276 consecutive patients diagnosed with HFrEF. Nutritional status was assessed using Mini Nutritional Assessment (MNA), geriatric nutritional risk index (GNRI), and body mass index (BMI). The mean follow-up period was 564.4 ± 346.3 days. The analysed group included 81.2% of men. The median age was 58, interquartile range (IQR) 49–64 years. Among all patients, almost 60% were classified as NYHA III or IV. Half of the participants were at risk of malnutrition, and 2.9% were malnourished. During follow-up, 72 (26.1%) patients died. The female sex was not associated with a higher occurrence of malnutrition (P = 0.99) or nutritional risk (P = 0.85), according to MNA. Coherently, GNRI scores did not differ significantly between the sexes (P = 0.29). In contrast, BMI was significantly higher in males (29.4 ± 5.3 vs. 25.9 ± 4.7; P < 0.001). Impaired nutritional status assessed with any method (MNA, GNRI, BMI) was not significantly associated with a worse prognosis. In multivariable analysis, NYHA class, lower estimated glomerular filtration rate, higher B-type natriuretic peptide (BNP), higher N-terminal fragment of proBNP, and higher uric acid were independent of sex and age predictors of all-cause mortality.

Conclusion

There were no sex differences in the nutritional status in the HFrEF patients, apart from lower BMI in females. Impaired nutritional status was not associated with mortality in both men and women.
Health economics in nursing research: what you need to know to include economic evaluation methodology in your research
Authors: Bulamu Norma B , Kaambwa Billingsley , Beks Hannah , Versace Vincent L , Clark Robyn A
Published: January 2024

Due to limited resources and constant, ever-changing healthcare challenges, health economics is essential to support healthcare decisions while improving health outcomes. Economic evaluation methodology facilitates informed decision-making related to the efficient allocation of resources while positively impacting clinical practice. In this paper, we provide an overview of economic evaluation methods and a real-world example applying one method of economic evaluation (cost-utility analysis) in nursing research.
Advanced metabolic engineering strategies for increasing artemisinin yield in Artemisia annua L.
Authors: Li Yongpeng , Yang Yinkai , Li Ling , Tang Kexuan , Hao Xiaolong , Kai Guoyin
Published: January 2024

Artemisinin, also known as ‘Qinghaosu’, is a chemically sesquiterpene lactone containing an endoperoxide bridge. Due to the high activity to kill Plasmodium parasites, artemisinin and its derivatives have continuously served as the foundation for antimalarial therapies. Natural artemisinin is unique to the traditional Chinese medicinal plant Artemisia annua L., and its content in this plant is low. This has motivated the synthesis of this bioactive compound using yeast, tobacco, and Physcomitrium patens systems. However, the artemisinin production in these heterologous hosts is low and cannot fulfil its increasing clinical demand. Therefore, A. annua plants remain the major source of this bioactive component. Recently, the transcriptional regulatory networks related to artemisinin biosynthesis and glandular trichome formation have been extensively studied in A. annua. Various strategies including (i) enhancing the metabolic flux in artemisinin biosynthetic pathway; (ii) blocking competition branch pathways; (iii) using transcription factors (TFs); (iv) increasing peltate glandular secretory trichome (GST) density; (v) applying exogenous factors; and (vi) phytohormones have been used to improve artemisinin yields. Here we summarize recent scientific advances and achievements in artemisinin metabolic engineering, and discuss prospects in the development of high-artemisinin yielding A. annua varieties. This review provides new insights into revealing the transcriptional regulatory networks of other high-value plant-derived natural compounds (e.g., taxol, vinblastine, and camptothecin), as well as glandular trichome formation. It is also helpful for the researchers who intend to promote natural compounds production in other plants species.
Non-asymptotic analysis of ensemble Kalman updates: effective dimension and localization
Authors: Al-Ghattas Omar , Sanz-Alonso Daniel
Published: December 2023

Many modern algorithms for inverse problems and data assimilation rely on ensemble Kalman updates to blend prior predictions with observed data. Ensemble Kalman methods often perform well with a small ensemble size, which is essential in applications where generating each particle is costly. This paper develops a non-asymptotic analysis of ensemble Kalman updates, which rigorously explains why a small ensemble size suffices if the prior covariance has moderate effective dimension due to fast spectrum decay or approximate sparsity. We present our theory in a unified framework, comparing several implementations of ensemble Kalman updates that use perturbed observations, square root filtering and localization. As part of our analysis, we develop new dimension-free covariance estimation bounds for approximately sparse matrices that may be of independent interest.
A unified recovery of structured signals using atomic norm
Authors: Chen Xuemei
Published: December 2023

In many applications, we seek to recover signals from linear measurements far fewer than the ambient dimension, given the signals have exploitable structures such as sparse vectors or low rank matrices. In this paper, we work in a general setting where signals are approximately sparse in a so-called atomic set. We provide general recovery results stating that a convex programming can stably and robustly recover signals if the null space of the sensing map satisfies certain properties. Moreover, we argue that such null space property can be satisfied with high probability if each measurement is sub-Gaussian even when the number of measurements are very few. Some new results for recovering signals sparse in a frame, and recovering low rank matrices are also derived as a result.
Sigma-Delta and distributed noise-shaping quantization methods for random Fourier features
Authors: Zhang Jinjie , Kannan Harish , Cloninger Alexander , Saab Rayan
Published: December 2023

We propose the use of low bit-depth Sigma-Delta and distributed noise-shaping methods for quantizing the random Fourier features (RFFs) associated with shift-invariant kernels. We prove that our quantized RFFs—even in the case of $1$-bit quantization—allow a high-accuracy approximation of the underlying kernels, and the approximation error decays at least polynomially fast as the dimension of the RFFs increases. We also show that the quantized RFFs can be further compressed, yielding an excellent trade-off between memory use and accuracy. Namely, the approximation error now decays exponentially as a function of the bits used. The quantization algorithms we propose are intended for digitizing RFFs without explicit knowledge of the application for which they will be used. Nevertheless, as we empirically show by testing the performance of our methods on several machine learning tasks, our method compares favourably with other state-of-the-art quantization methods.
P01 Who’s counting? How many IV antibiotic administrations are given daily at four Midlands trusts
Authors: Jenkins Abi , Hussain Sadiya , Gilani Syed , Ashton Corrine
Published: January 2024

Background

Up to 80% of patients admitted to hospital receive IV therapy during their stay.1 In the UK, the NHS England Commissioning for Quality and Innovation (CQUIN) audit for quarter 1 of 2023–24 in the Midlands shows that 9.1%–35.0% of patients prescribed IV antibiotics are appropriate for a switch to oral therapy. A recent time and motion study demonstrated that IV medicine administration takes 20 min longer to give than an oral preparation.2 Consequently, an appropriate IV to oral switch releases 20 min of nurse time per dose administered. The unknown parameter is ‘how many antibiotic injections are given daily in hospitals’. Quantifying this parameter would enable Trusts to calculate the workforce capacity that could be realized on implementing an effective IVOS pathway.

Methods

The number of IV antibiotics administered to inpatients was determined on one day for seven consecutive weeks at four Midlands trusts. In Week 1, data were collected on Sunday, Week 2 on Monday and so on until Week 7 on Saturday. Finally, the ratio of number of IV antibiotics doses per number of occupied beds was determined.

Results

The range of the number of doses administered per occupied beds was between 0.92 and 1.18; it would be reasonable therefore to use the approximation of the number of antibiotic injections given daily at the four trusts as one injection per occupied bed. Taking a pragmatic approach that 20% of IV doses could be given orally with each change to oral releasing 20 min per administration we are proposing a calculation for the potential workforce released if an effective IVOS pathway is implemented: number of workforce hours released/day=number of trust beds/15.

Conclusions

Implementation of an effective IVOS pathway has the potential to release a significant number of hours each day to nurses to undertake other tasks.
P11 Spectrum of ceftriaxone/levofloxacin use by Ukrainians and foreigners settled in Ukraine
Authors: Myroniuk-Konstantynovych Kiarina , Bondaruk Iryna , Bevz Tetiana , Demchyshyn Yaroslav , Konstantynovych Tetyana
Published: January 2024

Background

The use of multiple broad-spectrum antibiotics (such as ceftriaxone and levofloxacin) is not evidence-based, nor recommended in high-quality international guidelines. Therefore, WHO does not recommend their use in clinical practice (AWaRe classification of antibiotics for evaluation and monitoring of use, 2023). It created the necessity of an order of the Ministry of Health (dated 23 August 2023) in Ukraine. Therefore, the studying of prohibited antibiotic use is quite relevant.

Objectives

To investigate the frequency and expediency of using ceftriaxone and levofloxacin among Ukrainian and foreigners settled in Ukraine.

Subjects and methods

A total of 180 responders (63.9% female, 36.1% male; average age 18–25 years) were tested by self-administered questionnaire according to national/geographical and comorbid anamnesis and ceftriaxone/levofloxacin (C/L) use anamnesis over a 1 year period. The incidence, intensity and efficacy of antibiotic use were evaluated.

Results

The sample included 56.1% Ukrainians and 43.9% international citizens, predominantly from the African continent and India. Both groups were not significantly different according to age, gender and comorbid pathology distributions (P>0.05). Anamnesis of C/L separate or combined use was identified in 12.74% Ukrainians and 58.97% foreigners (P<0.001). The multiplicity of antibiotic use >2 courses/year was determined more often among foreigners (P<0.05). The inefficacy of antibiotic therapy among foreigners was 67.4% versus 33.1% among Ukrainians (P<0.05).

Conclusions

Despite C/L not being recommended according to AWaRe (2023), the frequency of use is still significantly high among foreigners. Therefore, causal relationships need to be studied further.
P12 Unjustified use of antibiotics in wartime conditions in Ukraine
Authors: Myroniuk-Konstantynovych Kiarina , Bondaruk Iryna , Bevz Tetiana , Demchyshyn Yaroslav , Konstantynovych Tetyana
Published: January 2024

Background

The Ministry of Health of Ukraine reported that every second patient who takes antibiotics does not need such treatment, and every third uses them for viral diseases. In Ukraine, during the war, there has formed a resonance between the availability of broad-spectrum antibiotics and their belonging to the non-recommended category according to the AWaRe classification 2023. Therefore, the fight against antibiotic resistance continues to be a leading task of modern medicine.

Objectives

To investigate the expediency of use of ceftriaxone/levofloxacin among Ukrainian and foreigners settled in Ukraine.

Subjects and methods

A total of 180 (55% Ukrainians, 45% foreigners) responders were examined by questionnaire for ceftriaxone/levofloxacin use over 1 year with specification of reasons, expediency of use, possible reason for cancellation/replacement of antibiotic therapy and preventable usage cases.

Results

The sample included 63.9% women, 36.1% men, average age 18–25 years. The incidence of ceftriaxone/levofloxacin use was 58.97% among foreigners versus 12.74% among Ukrainians (P<0.001). The antibiotic use by physician’s prescription occurred among 28.3% foreigners and 92.3% Ukrainians (P < 0.05). The frequency of antibiotic use due to microbiological confirmation was significantly lower among foreign responders: 13.05% versus 76.9% in Ukrainians (P < 0.01). The reasons for choice of ceftriaxone/levofloxacin in the Ukrainian sample were acute respiratory infections 46%, fever 7.8% and diseases of bacterial origin 84.6%. At the same time foreigners used antibiotics for acute respiratory infections 41.3%, fever 19.7% and diseases of bacterial origin 63.1%. The analysis found that antibiotic use for ‘prophylaxis’ (mainly for viral diseases) was 2.95% among Ukrainians and 32.05% among foreigners (P<0.05). The predominant reasons for cancellation/replacement of antibiotic therapy, such as allergic reactions and antibiotic-associated diarrhoea, were found in 67.4% of foreigners and 7.69% of Ukrainians (P<0.05).

Conclusions

The lack of antibiotic prescription on the basis of microbiological confirmation, self-limited choice of antibiotics and unreasonable use for diseases of non-bacterial origin can be factors that promote multiple resistance in future and complicate the natural clinical course of most common infectious diseases.
P25 Nowhere to hide: broad-spectrum antimicrobial guideline adherence in outpatients
Authors: Razaq Shahzad , Raza Waqar , Jenkins Abigail
Published: January 2024

Background

The NHS Acute Trusts Standard1 contract requires a 10% reduction in broad-spectrum antibiotics by 10% by March 2024 from a 2017 baseline. Co-amoxiclav is a broad-spectrum antibacterial that comprises 30% of broad-spectrum consumption at University Hospitals Birmingham. It is widely used across all specialities and is a perfect candidate to review to influence downward trend in consumption. Outpatient prescriptions do not receive the same level of scrutiny from pharmacy or antimicrobial stewardship team as inpatient prescriptions. If deviations from guidelines are identified, then this could be a potential area to address to reduce consumption.

Methods

Sixty outpatient co-amoxiclav prescriptions were reviewed to assess appropriateness of prescribing during December 2022. Parameters assessed included the indication and duration of co-amoxiclav therapy and adherence to Trust antimicrobial guidelines. The speciality prescribing outpatient co-amoxiclav was also documented to identify whether prescribing trends could be identified.

Results

Of 60 reviewed outpatient prescriptions written in December 2022, 54 were issued by acute medicine with other specialities including cardiothoracic, renal medicine, elderly care, ENT, urology and cardiology. All prescriptions had a documented indication and duration, however only three were adherent to Trust antimicrobial guidelines. The graph below represents the different indications co-amoxiclav was prescribed for to outpatients across all three hospital sites. Co-amoxiclav was most frequently prescribed for respiratory tract infections, followed by skin and then urinary tract infections.

Conclusions

This audit has highlighted that outpatient co-amoxiclav is commonly prescribed inappropriately and does not comply with Trust antimicrobial guidelines. The speciality most frequently prescribing outpatient co-amoxiclav inappropriately was acute and emergency medicine. The lack of clarity regarding the infection indication is a potentially important factor in this setting, resulting in broad-spectrum antimicrobial use to cover multiple potential bacterial infections. A limitation of this audit is it was carried out over a short and busy winter period.
Applications of Digital Polymerase Chain Reaction (dPCR) in Molecular and Clinical Testing
Authors: Wainman Lauren M , Sathyanarayana Shivaprasad H , Lefferts Joel A
Published: January 2024

Background

Digital polymerase chain reaction (dPCR) is an accurate and sensitive molecular method that can be used in clinical diagnostic, prognostic, and predictive tests. The key component of the dPCR method is the partitioning of a single reaction into many thousands of droplets, nanochannels or other nano- or picoliter-sized reactions. This results in high enough sensitivity to detect rare nucleic acid targets and provides an absolute quantification of target sequences or alleles compared to other PCR-based methods.

Content

An increasing number of dPCR platforms have been introduced commercially in recent years and more are being developed. These platforms differ in the method of partitioning, degree of automation, and multiplexing capabilities but all can be used in similar ways for sensitive and highly accurate quantification of a variety of nucleic acid targets. Currently, clinical applications of dPCR include oncology, microbiology and infectious disease, genetics, and prenatal/newborn screening. Commercially available tests for clinical applications are being developed for variants with diagnostic, prognostic, and therapeutic significance in specific disease types.

The power of dPCR technology relies on the partitioning of the reactions and results in increased sensitivity and accuracy compared to qPCR. More recently, the sensitivity of dPCR has been applied to the detection of known variants in cell-free DNA and circulating tumor DNA. Future clinical applications of dPCR include liquid biopsy, treatment resistance detection, screening for minimal residual disease, and monitoring allograft engraftment in transplanted patients.
Protection against unfair competition in the Andean Community—an analysis of recent trends and developments
Authors: Bermeo Andrade Rodrigo V
Published: January 2024

The general concepts of free trade and unfair competition are regulated by Andean Community decisions. National legislation provides more detailed regulations. Andean Community Decision 608 promotes and protects free competition across the region. The scope of application of this Decision is limited to practices that have origin and effects in one or more Andean Community countries. Local transactions within the country must observe internal legislation. While Andean law covers cross-border transactions, intra-country operations are governed by local bodies of law. There are yet not many decisions at the Andean level, but the local agencies in Colombia, Ecuador and Peru have issued several decisions that dig into the different elements of unfair acts. The following analysis provides an overview of protection against unfair competition in the region and sheds light on current developments.
Increasing radiation therapy and lower survival for human papillomavirus–related oropharynx cancer associated with a shift to community cancer center care
Authors: Trakimas Danielle R , Mydlarz Wojtek , Mady Leila J , Koch Wayne , Quon Harry , London Nyall R , Fakhry Carole
Published: January 2024

Background

Studies have shown lower overall survival for patients with head and neck cancer treated at low-volume or community cancer centers. As the incidence of human papillomavirus (HPV)–related oropharyngeal squamous cell carcinoma steadily rises in the United States, we hypothesized that a greater proportion of patients with HPV-related oropharyngeal squamous cell carcinoma is being treated at community cancer centers, with a shift toward primary nonsurgical treatment.

Methods

This cohort study included patients from the US National Cancer Database who received a diagnosis of HPV-related oropharyngeal squamous cell carcinoma from 2010 to 2019 and underwent treatment at a community cancer center or academic cancer center. The proportion of patients with HPV-related oropharyngeal squamous cell carcinoma treated at community cancer centers and receiving primary nonsurgical treatment was analyzed over time. Four-year overall survival was compared between community cancer centers and academic cancer centers.

Results

The majority (67.4%) of 20 298 patients were treated at an academic cancer center, yet the proportion of patients treated at community cancer centers increased by 10% from 2010 to 2019 (P < .01 for trend). The proportion of patients undergoing primary nonsurgical treatment increased from 62.1% to 73.7% from 2010 to 2019 (P < .01 for trend), and patients were statistically significantly more likely to undergo nonsurgical treatment at community cancer centers than at academic cancer centers (adjusted odds ratio = 1.20, 95% confidence interval = 1.18 to 1.22). Treatment at community cancer centers was associated with worse survival overall (adjusted hazard ratio = 1.19, 95% confidence interval = 1.09 to 1.31), specifically for patients receiving primary nonsurgical treatment (adjusted hazard ratio = 1.22, 95% confidence interval = 1.11 to 1.34).

Conclusions

Treatment of HPV-related oropharyngeal squamous cell carcinoma has recently shifted to community cancer centers, with an increase in the proportion of nonsurgical treatment and worse overall survival at these centers compared with academic cancer centers. Concentration of care for HPV-related oropharyngeal squamous cell carcinoma at academic cancer centers and dedicated head and neck cancer centers may increase access to all available treatment modalities and improve survival.
Evaluation of the mannan antigen assay in neonates with or without Candida albicans colonization
Authors: Bourika Vasiliki , Siahanidou Tania , Theodoridou Kalliopi , Tsakris Athanasios , Vrioni Georgia , Michos Athanasios
Published: January 2024

Mannan antigen (MA) in neonates as a marker of invasive candidemia is not well studied, although 4% of all neonatal intensive care unit admissions are attributed to Candida spp. infections. The aim of this case-control study was to evaluate the performance of MA (Platelia™ Candida AgPluskit, Bio-Rad) in neonates who had rectal Candida colonization or in non-colonized controls. We cultured 340 rectal swabs of neonates and MA was negative in 24/25 C. albicans colonized (96% specificity) and in 30/30 non-colonized neonates (100% specificity). The results indicate a high specificity of the assay, which could be useful in neonates with possible candidemia.
Characterization of the repeating FRB 20220912A with the Allen Telescope Array
Authors: Sheikh Sofia Z , Farah Wael , Pollak Alexander W , Siemion Andrew P V , Chamma Mohammed A , Cruz Luigi F , Davis Roy H , DeBoer David R , Gajjar Vishal , Karn Phil , Kittling Jamar , Lu Wenbin , Masters Mark , Premnath Pranav , Schoultz Sarah , Shumaker Carol , Singh Gurmehar , Snodgrass Michael
Published: January 2024

FRB 20220912A is a repeating Fast Radio Burst (FRB) that was discovered in Fall 2022 and remained highly active for several months. We report the detection of 35 FRBs from 541 h of follow-up observations of this source using the recently refurbished Allen Telescope Array, covering 1344 MHz of bandwidth primarily centred at 1572 MHz. All 35 FRBs were detected in the lower half of the band with non-detections in the upper half and covered fluences from 4–431 Jy-ms (median = 48.27 Jy-ms). We find consistency with previous repeater studies for a range of spectrotemporal features including: bursts with downward frequency drifting over time; a positive correlation between bandwidth and centre frequency; and a decrease in sub-burst duration over time. We report an apparent decrease in the centre frequency of observed bursts over the two months of the observing campaign (corresponding to a drop of 6.21 ± 0.76 MHz per d). We predict a cut-off fluence for FRB 20220912A of Fmax ≲ 104 Jy-ms, for this source to be consistent with the all-sky rate, and find that FRB 20220912A significantly contributed to the all-sky FRB rate at a level of a few per cent for fluences of ∼100 Jy-ms. Finally, we investigate characteristic time-scales and sub-burst periodicities and find (a) a median inter-subburst time-scale of 5.82 ± 1.16 ms in the multi-component bursts and (b) no evidence of strict periodicity even in the most evenly spaced multi-component burst in the sample. Our results demonstrate the importance of wideband observations of FRBs, and provide an important set of observational parameters against which to compare FRB progenitor and emission mechanism models.
Two-motif model illuminates DICER cleavage preferences
Authors: Le Cong Truc , Nguyen Trung Duc , Nguyen Tuan Anh
Published: January 2024

In humans, DICER is a key regulator of gene expression through its production of miRNAs and siRNAs by processing miRNA precursors (pre-miRNAs), short-hairpin RNAs (shRNAs), and long double-stranded RNAs (dsRNAs). To advance our understanding of this process, we employed high-throughput dicing assays using various shRNA variants and both wild-type and mutant DICER. Our analysis revealed that DICER predominantly cleaves shRNAs at two positions, specifically at 21 (DC21) and 22 (DC22) nucleotides from their 5′-end. Our investigation identified two different motifs, mWCU and YCR, that determine whether DICER cleaves at DC21 or DC22, depending on their locations in shRNAs/pre-miRNAs. These motifs can work together or independently to determine the cleavage sites of DICER. Furthermore, our findings indicate that dsRNA-binding domain (dsRBD) of DICER enhances its cleavage, and mWCU strengthens the interaction between dsRBD and RNA, leading to an even greater enhancement of the cleavage. Conversely, YCR functions independently of dsRBD. Our study proposes a two-motif model that sheds light on the intricate regulatory mechanisms involved in gene expression by elucidating how DICER recognizes its substrates, providing valuable insights into this critical biological process.
Pulmonary Function and Survival 1 Year After Dupilumab Treatment of Acute Moderate to Severe Coronavirus Disease 2019: A Follow-up Study From a Phase 2a Trial
Authors: Hendrick Jennifer , Ma Jennie Z , Haughey Heather M , Coleman Rachael , Nayak Uma , Kadl Alexandra , Sturek Jeffrey M , Jackson Patrick , Young Mary K , Allen Judith E , Petri William A
Published: January 2024

Background

We previously conducted a phase 2a randomized placebo-controlled trial of 40 subjects to assess the efficacy and safety of dupilumab use in people hospitalized with coronavirus disease 2019 (COVID-19) (NCT04920916). Based on our preclinical data suggesting that downstream pulmonary dysfunction with COVID-19 induced type 2 inflammation, we contacted patients from our phase 2a study at 1 year for assessment of post-COVID-19 conditions.

Methods

Subjects at 1 year after treatment underwent pulmonary function tests, high-resolution computed tomographic imaging, symptom questionnaires, neurocognitive assessments, and serum immune biomarker analysis, with subject survival also monitored. The primary outcome was the proportion of abnormal diffusion capacity for carbon monoxide (DLCO) or 6-minute walk test (6MWT) at the 1-year visit.

Results

Of those survivors who consented to 1-year visits (n = 16), subjects who had originally received dupilumab were less likely than those who received placebo to have an abnormal DLCO or 6MWT (Fisher exact P = .011; adjusted P = .058). As a secondary endpoint, we saw that 16% of subjects in the dupilumab group died by 1 year compared to 38% in the placebo group, though this was not statistically significant (log-rank P = .12). We did not find significant differences in neurocognitive testing, symptoms, or chest computed tomography between treatment groups but observed a larger reduction in eotaxin levels in those who received dupilumab.

Conclusions

In this observational study, subjects who received dupilumab during acute COVID-19 hospitalization were less likely to have a reduced DLCO or 6MWT, with a nonsignificant trend toward reduced mortality at 1 year compared to placebo.