Bundgaardmalling3314
clinical judgment and close monitoring are needed. This paper was approved by the ASPEN Board of Directors.Indole-3-acetic acid (IAA) synthesis is a major property of rhizosphere bacteria. The IAA-producing ability of rhizobacteria may be influenced by agricultural management. We therefore evaluated the IAA-producing potential of rhizobacteria isolated during organic rice farming (ORF) and conventional rice farming (CRF) in Thung Kula Rong Hai areas of Thailand. The results indicated that ORF gave a significantly higher percentage of IAA producers (95·8%) than CRF (69·9%). The average IAA values of the ORF isolates were around two times higher than those of the CRF isolates both in the absence (12·8 and 5·8 μg IAA ml-1 , respectively) and presence of L-tryptophan (L-Trp) (35·2 and 17·2 μg IAA ml-1 , respectively). The 16S rRNA gene sequence analysis indicated that the 23 selected isolates belonged to 8 different genera-Sinomonas sp., Micrococcus sp., Microbacterium sp., Fictibacillus sp., Bacillus sp., Burkholderia sp., Leclercia sp. and Enterobacter sp. mTOR inhibitor Interestingly, only three ORF isolates, i.e. link2 ORF15-20 (Micrococcus sp.), ORF15-21 (Sinomonas sp.) and ORF15-23 (Sinomonas sp.), exhibited high IAA production ability without L-Trp (128·5, 160·8 and 174·7 μg IAA ml-1 , respectively). Meanwhile, a slight decrease in IAA production with L-Trp was noticed, suggesting that the L-Trp was not used for the IAA synthesis of these isolates. Biopriming with rhizobacterial isolates significantly enhanced the rate of germination of KDML 105 rice seeds compared to the control.For many years, lipid nanoparticles (LNPs) have been used as delivery vehicles for various payloads (especially various oligonucleotides and mRNA), finding numerous applications in drug and vaccine development. LNP stability and bilayer fluidity are determined by the identities and the amounts of the various lipids employed in the formulation and LNP efficacy is determined in large part by the lipid composition which usually contains a cationic lipid, a PEG-lipid conjugate, cholesterol, and a zwitterionic helper phospholipid. Analytical methods developed for LNP characterization must be able to determine not only the identity and content of each individual lipid component (i.e., the parent lipids), but also the associated impurities and degradants. In this work, we describe an efficient and sensitive reversed-phase chromatographic method with charged aerosol detection (CAD) suitable for this purpose. Sample preparation diluent and mobile phase pH conditions are critical and have been optimized for the lipids of interest. This method was validated for its linearity, accuracy, precision, and specificity for lipid analysis to support process and formulation development for new drugs and vaccines.Salivary gland tumours present a pleomorphic and complex morphology and, apart from the most common neoplasms with well-established histopathological criteria, may create diagnostic difficulty for histopathologists. The majority of salivary gland tumours occur in the parotid gland and the use of ultrasound guided parotid biopsy (US-PB) has increased. US-PB in contrast with fine needle aspiration (FNA), which is an easy and relatively painless technique, is performed under local anaesthesia, usually by radiologists. US-PB offers some advantages over the FNA such as tumour grading and the possibility of performing immunohistochemistry. We report our experience of the diagnostic value of US-PB in a large, referral centre in the United Kingdom.The evolutionary and ecological story of coccolithophores poses questions about their heterotrophy, surviving darkness after the end-Cretaceous asteroid impact as well as survival in the deep ocean twilight zone. Uptake of dissolved organic carbon might be an alternative nutritional strategy for supply of energy and carbon molecules. Using long-term batch culture experiments, we examined coccolithophore growth and maintenance on organic compounds in darkness. Radiolabelled experiments were performed to study the uptake kinetics. Pulse-chase experiments were used to examine the uptake into unassimilated, exchangeable pools vs assimilated, nonexchangeable pools. We found that coccolithophores were able to survive and maintain their metabolism for up to 30 d in darkness, accomplishing about one cell division. The concentration dependence for uptake was similar to the concentration dependence for growth in Cruciplacolithus neohelis, suggesting that it was taking up carbon compounds and immediately incorporating them into biomass. We recorded net incorporation of radioactivity into the particulate inorganic fraction. We conclude that osmotrophy provides nutritional flexibility and supports long-term survival in light intensities well below threshold for photosynthesis. The incorporation of dissolved organic matter into particulate inorganic carbon, raises fundamental questions about the role of the alkalinity pump and the alkalinity balance in the sea.
Nivolumab plus ipilimumab (NIVO + IPI) has demonstrated long-term efficacy and safety in patients with previously untreated, advanced renal cell carcinoma (aRCC). link3 Although most phase 3 clinical trials exclude patients with brain metastases, the ongoing, multicohort phase 3b/4 CheckMate 920 trial (ClincalTrials.gov identifier NCT02982954) evaluated the safety and efficacy of NIVO + IPI in a cohort that included patients with aRCC and brain metastases, as reported here.
Patients with previously untreated aRCC and asymptomatic brain metastases received NIVO 3mg/kg plus IPI 1mg/kg every 3weeks × 4 followed by NIVO 480mg every 4weeks. The primary end point was the incidence of grade ≥3 immune-mediated adverse events (imAEs) within 100days of the last dose of study drug. Key secondary end points were progression-free survival and the objective response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1 (both determined by the investigator). Exploratory end points included overall surviverrepresented in clinical trials-the approved regimen of NIVO + IPI followed by NIVO showed encouraging antitumor activity and no new safety signals.
Phonation threshold pressure (P
) is the minimum subglottic pressure required to reach phonation onset and is considered a marker for vocal efficiency and health. We investigated the effects of intrinsic laryngeal muscle (ILM) activation on P
.
In vivo animal study.
In an in vivo canine phonation model, laryngeal adductor muscles were activated together by stimulation of the recurrent laryngeal nerves (RLNs) and individually via stimulation of respective terminal nerve branches. Cricothyroid (CT) muscles were activated via stimulation of the superior laryngeal nerves. ILMs were activated in a graded manner at various combinations as transglottal airflow was gradually increased. Aerodynamic and glottal posture parameters were measured at phonation onset.
Graded RLN stimulation decreased glottal distance and increased P
. Thyroarytenoid (TA) muscle activation alone increased P
. Lateral cricoarytenoid (LCA) muscle activation alone had minimal effects. However, graded TA activation as a function of LCA activation level revealed a synergistic relationship between the two muscles in increasing P
. Effects of CT activation were dependent on adductor stimulation level CT activation increased P
at low RLN stimulation levels and decreased P
at high RLN levels.
The effects of ILM activation on P
were consistent with their expected effects on vocal fold stiffness and tension. TA was the primary adductor controlling P
. While LCA alone had minimal effects on P
, it enhanced the role of TA in controlling P
. TA and CT have antagonistic roles in controlling P
. These relationships should be considered in clinical efforts to improve ease of phonation and vocal efficiency.
N/A, basic science Laryngoscope, 2021.
N/A, basic science Laryngoscope, 2021.
The demand and supply of blood are highly variable over time. Blood inventory management that relies heavily on experience-based decisions may not be adaptive to real demand, leading to high operational costs, wastage, and shortages.
We combined statistical modeling, machine learning, and optimization methods to develop a data-driven demand forecasting and inventory management strategy for red blood cells (RBCs). We then used the strategy to inform daily blood orders. A secondary semi-weekly (twice per week) ordering strategy was developed to handle the last-mile split delivery problem for blood suppliers, characterized by multi-deliveries to the same location multiple times during a short period of time. Both strategies were evaluated using the TRUST database including all patient data across four hospitals in Hamilton, Ontario.
We identified 227,944 RBC transfusions for 40,787 patients in Hamilton, Ontario from 2012 to 2018. The predicted daily demand from the hybrid demand forecasting model was not significantly different from the actual daily demand (paired t-test p-value=0.163); however, the proposed daily ordering quantity from the model was significantly lower than the actual ordering quantity (p-value <0.001). The proposed daily ordering strategy reduced inventory levels by 38.4% without risk of shortages, leading to an overall cost reduction of 43.0% (95% confidence interval [CI] 42.3%, 43.7%) compared with the actual cost. The semi-weekly ordering strategy reduced ordering frequency by 62.6% (95% CI 61.5%, 63.7%).
The proposed data-driven ordering strategy combining demand forecasting and inventory optimization can achieve significant cost savings for healthcare systems and blood suppliers.
The proposed data-driven ordering strategy combining demand forecasting and inventory optimization can achieve significant cost savings for healthcare systems and blood suppliers.Antimicrobial resistance is threatening to overshadow last century's medical advances. Etiological agents of previously eradicated infectious diseases are now resurgent as multidrug-resistant strains, especially for Gram-negative strains. Finding new therapeutic solutions is a real challenge for our society. In this framework, Photodynamic Antimicrobial ChemoTherapy relies on the generation of toxic reactive oxygen species in the presence of light, oxygen, and a photosensitizer molecule. The use of reactive oxygen species is common for disinfection processes, using chemical agents, such as chlorine and hydrogen peroxide, and as they do not have a specific molecular target, it decreases the potential of tolerance to the antimicrobial treatment. However, light-driven generated reactive species result in an interesting alternative, as reactive species generation can be easily tuned with light irradiation and several PSs are known for their low environmental impact. Over the past few years, this topic has been thoroughly studied, exploring strategies based on single-molecule PSs (tetrapyrrolic compounds, dipyrrinate derivatives, metal complexes, etc.) or on conjunction with delivery systems. The present work describes some of the most relevant advances of the last 6 years, focusing on photosensitizers design, formulation, and potentiation, aiming for the disinfection of Gram-negative bacteria.
