Shaping single crystalline BaTiO3nanostructures by focused neon or helium ion milling.

The realization of perovskite oxide nanostructures with controlled shape and dimensions remains a challenge. Here, we investigate the use of helium and neon focused ion beam (FIB) milling in an ion microscope to fabricate BaTiO3nanopillars of sub-500 nm in diameter starting from BaTiO3(001) single crystals. Irradiation of BaTiO3with He ions induces the formation of nanobubbles inside the material, eventually leading to surface swelling and blistering. Ne-FIB is shown to be suitable for milling without inducing surface swelling. The resulting structures are defect-free single crystal nanopillars, which are enveloped, on the top and lateral sidewalls, by a point defect-rich crystalline region and an outer Ne-rich amorphous layer. The amorphous layer can be selectively etched by dipping in diluted HF. The geometry and beam-induced damage of the milled nanopillars depend strongly on the patterning parameters and can be well controlled. Ne ion milling is shown to be an effective method to rapidly prototype BaTiO3crystalline nanostructures.

Improved Magneto-Microfluidic Separation of Nanoparticles through Formation of the ß-Cyclodextrin-Curcumin Inclusion Complex.

Molecular adsorption to the nanoparticle surface may switch the colloidal interactions from repulsive to attractive and promote nanoparticle agglomeration. If the nanoparticles are magnetic, then their agglomerates exhibit a much stronger response to external magnetic fields than individual nanoparticles. Coupling between adsorption, agglomeration, and magnetism allows a synergy between the high specific area of nanoparticles (∼100 m2/g) and their easy guidance or separation by magnetic fields. This yet poorly explored concept is believed to overcome severe restrictions for several biomedical applications of magnetic nanoparticles related to their poor magnetic remote control. In this paper, we test this concept using curcumin (CUR) binding (adsorption) to ß-cyclodextrin (ßCD)-coated iron oxide nanoparticles (IONP). CUR adsorption is governed by host-guest hydrophobic interactions with ßCD through the formation of 1:1 and, possibly, 2:1 ßCD:CUR inclusion complexes on the IONP surface. A 2:1 stoichiometry is supposed to promote IONP primary agglomeration, facilitating the formation of the secondary needle-like agglomerates under external magnetic fields and their magneto-microfluidic separation. The efficiency of these field-induced processes increases with CUR concentration and ßCD surface density, while their relatively short timescale (<5 min) is compatible with magnetic drug delivery application.

Biophysics and protein corona analysis of Janus cyclodextrin-DNA nanocomplexes. Efficient cellular transfection on cancer cells.

The self-assembling processes underlining the capabilities of facially differentiated ("Janus") polycationic amphiphilic cyclodextrins (paCDs) as non-viral gene nanocarriers have been investigated by a pluridisciplinary approach. Three representative Janus paCDs bearing a common tetradecahexanoyl multitail domain at the secondary face and differing in the topology of the cluster of amino groups at the primary side were selected for this study. All of them compact pEGFP-C3 plasmid DNA and promote transfection in HeLa and MCF-7 cells, both in absence and in presence of human serum. The electrochemical and structural characteristics of the paCD-pDNA complexes (CDplexes) have been studied by using zeta potential, DLS, SAXS, and cryo-TEM. paCDs and pDNA, when assembled in CDplexes, render effective charges that are lower than the nominal ones. The CDplexes show a self-assembling pattern corresponding to multilamellar lyotropic liquid crystal phases, characterized by a lamellar stacking of bilayers of the CD-based vectors with anionic pDNA sandwiched among them. When exposed to human serum, either in the absence or in the presence of pDNA, the surface of the cationic CD-based vector becomes coated by a protein corona (PC) whose composition has been analyzed by nanoLC-MS/MS. Some of the CDplexes herein studied showed moderate-to-high transfection levels in HeLa and MCF-7 cancer cells combined with moderate-to-high cell viabilities, as determined by FACS and MTT reduction assays. The ensemble of data provides a detail picture of the paCD-pDNA-PC association processes and a rational base to exploit the protein corona for targeted gene delivery on future in vivo applications.

Conformationally-locked C-glycosides: tuning aglycone interactions for optimal chaperone behaviour in Gaucher fibroblasts.

A series of conformationally locked C-glycosides based on the 3-aminopyrano[3,2-b]pyrrol-2(1H)-one (APP) scaffold has been synthesized. The key step involved a totally stereocontrolled C-Michael addition of a serine-equivalent C-nucleophile to tri-O-benzyl-2-nitro-D-galactal, previously published by the authors. Stereoselective transformations of the Michael adduct allowed us the synthesis of compounds with mono- or diantennated aglycone moieties and different topologies. In vitro screening showed highly selective inhibition of bovine liver ß-glucosidase/ß-galactosidase and specific inhibition of human ß-glucocerebrosidase among lysosomal glycosidases for compounds bearing palmitoyl chains in the aglycone, with a marked dependence of the inhibition potency upon their number and location. Molecular dynamics simulations highlighted the paramount importance of an optimal orientation of the hydrophobic substituent to warrant efficient non-glycone interactions, which are critical for the binding affinity. The results provide a rationale for the strong decrease of the inhibition potency of APP compounds on going from neutral to acidic pH. The best candidate was found to behave as pharmacological chaperone in Gaucher fibroblasts with homozygous N370S and F213I mutations, with enzyme activity enhancements similar to those encountered for the reference compound Ambroxol.

Correlations between changes in intestinal microbiota composition and performance parameters in broiler chickens.

Growing male Cobb broiler chickens were fed on diets supplemented with additives reported as able to influence intestinal microbiota composition. The diets used were a balanced commercial diet (no additive), inulin (20 g/kg), fructose caramel (FC, 20 g/kg) and the garlic derivative PTS-O (propyl propane thiosulfonate, 45 and 90 mg/kg diet). The composition of the intestinal microbiota was analysed by qPCR at different points of the intestinal tract, and a number of nutritional parameters were also determined. The relative amounts of bacteroides (bacteroides/total bacteria) in the ileal contents correlated (p < 0.05) positively with faecal NDF, ADF, hemicellulose and cellulose digestibility. The relative amounts of Escherichia-Shigella (Escherichia-Shigella/total bacteria) in the crop contents correlated (p = 0.05) negatively with weight gain of broilers. Faecal N digestibility correlated (p < 0.05) negatively with total bacteria in the ileal contents of chickens. The relative amounts of Escherichia-Shigella (Escherichia-Shigella/total bacteria) in the caecal contents correlated (p = 0.05) negatively with faecal fat digestibility of broilers. Total bacteria in ileal or caecal contents of growing chickens correlated (p < 0.05) negatively with ileal N digestibility. The results here reported suggest that positive or negative correlations can be found between performance parameters and changes in intestinal microbiota composition of growing broiler chickens.

The management of paediatric acute pain in Spain in 2021: Results of a national survey among paediatric anaesthesiologists.

OBJECTIVE: To improve knowledge about routine clinical practice in the management of paediatric acute pain in Spain. METHODS: A telematic survey was conducted via the Internet on a representative sample of healthcare professionals involved in the management of paediatric acute pain (specifically anaesthesiologists) in Spain. The survey included 28 questions about their usual clinical practice in the assessment and treatment of acute pain, and also training and organisational aspects in paediatric acute pain. RESULTS: The survey was completed during March 2021 by 150 specialists in anaesthesiology. The respondents widely experienced in the management of acute paediatric pain (mean years of experience: 14.3: SD: 7.8), essentially in acute postoperative pain (97% of cases). Although 80% routinely used validated paediatric acute pain assessment scales, only 2.6% used specific scales adapted for patients with cognitive impairment. Most of the respondents routinely used analgesic drugs such as paracetamol (99%) or metamizole (92%), but only 84% complemented these drugs with a loco-regional blocking technique or other non-steroidal anti-inflammatory drugs (62%). Furthermore, only 62.7% acknowledged having received specific training in paediatric acute pain, only 45% followed hospital institutional protocols, and a scant 28% did so through paediatric pain units. CONCLUSIONS: The survey identified important points for improvement in the training and organisation of acute pain management in Spanish paediatric patients.

Role of VV ECMO tracheal surgery and carinal resection: Two case reports.

The aim of this study is to describe the anaesthesia management of two patients undergoing carinal resection under veno-venous extracorporeal membrane oxygenation (VV ECMO). In both cases, anaesthesia was induced and then maintained with inhalational agents during pneumonectomy and mediastinoscopy (respectively). Then the jugular and femoral veins were cannulated and VV ECMO was started after heparinization. One of the patients presented bleeding during surgery, which was treated with low-dose vasopressors (norepinephrine) and transfusion of platelets, fresh frozen plasma, and concentrated red blood cells. During VV ECMO, anaesthesia was maintained with target-controlled infusion of propofol. VV ECMO can be expected to improve surgical conditions in tracheal surgery; however, it is still a novel technique in this context. In selected patients, it would guarantee ventilatory support during carinal resection, but it is essential to carefully plan anaesthesia maintenance and prepare for VV ECMO-related complications. This technique should only be used in tertiary centres with experience in VV ECMO management.

Description of Intensive Care and Intermediate Care resources managed by Anaesthesiology Departments in Spain and their adaptation capacity during the COVID-19 pandemic.

INTRODUCTION: It is essential to understand the strategic importance of intensive care resources in the sustainable organisation of healthcare systems. Our objective has been to identify the intensive and intermediate care beds managed by Anaesthesiology and Resuscitation Services (A-ICU and A-IMCU) in Spain, their human and technical resources, and the changes made to these resources during the COVID-19 pandemic. MATERIAL AND METHODS: Prospective observational study performed between December 2020 and July 2021 to register the number and characteristics of A-ICU and A-IMCU beds in hospitals listed in the catalogue published by the Spanish Ministry of Health. RESULTS: Data were obtained from 313 hospitals (98% of all hospitals with more than 500 beds, 70% of all hospitals with more than 100 beds). One hundred and forty seven of these hospitals had an A-ICU with a total of 1702 beds. This capacity increased to 2107 (124%) during the COVID-19 pandemic. Three hundred and eight hospitals had an A-IMCU with a total of 3470 beds, 52.9% (2089) of which provided long-term care. The hospitals had 1900 ventilators, at a ratio of 1.07 respirators per A-ICU; 1559 anaesthesiologists dedicated more than 40% of their working time to intensive care. The nurse-to-bed ratio in A-ICUs was 2.8. DISCUSSION: A large proportion of fully-equipped ICU and IMCU beds in Spanish hospitals are managed by the anaesthesiology service. A-ICU and A-IMCUs have shown an extraordinary capacity to adapt their resources to meet the increased demand for intensive care during the COVID-19 pandemic.

A pain in the pocket: Prevalence of pocket pain in patients with implantation of neuromodulation systems: A retrospective study.

INTRODUCTION: Implantable pulse generator (IPG) is a neurostimulation therapy mediated by electrodes and surgically implanted in a subcutaneous "pocket" used for the control of numerous pathologies. This study examines both the prevalence of pain associated with IPG implantation ("pain pocket syndrome") and its associated characteristics. MATERIALS AND METHODS: 56 patients with an IPG were included in the study. A health questionnaire was conducted to determine the presence of pain associated with the pocket and its neuropathic characteristics, as well as associated aesthetic concerns, location, situations that accentuate or alleviate pain, medications used for baseline and pocket pain control and other factors associated. RESULTS: Pain in the area of implantation of the IPG had a prevalence of 52.6% of patients (n = 27), in our sample, with a mean score on the visual analogic scale (VAS) of 4.9 points [3.9-5.8 points], with neuropathic characteristics in 53.3% (n = 16) of the patients with pain, with differences between the mean VAS score of the female (5.5 [4.3-5.8 points]) and males (3.5 points [2.1-4.9 points]) (p = 0.04). CONCLUSION: Pocket pain is a condition with a higher prevalence than described in previous studies, being of a higher intensity in females, involving a moderate pain in the area of implantation of the neuromodulating therapy. This pain has neuropathic characteristics and could require a repositioning intervention. Hence, more studies in this field should be carried to detect and prevent this syndrome.

Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR), Spanish Society of Emergency and Emergency Medicine (SEMES) and Spanish Society of Otolaryngology, Head and Neck Surgery (SEORL-CCC) Guideline for difficult airway management. Part I.

The Airway Management section of the Spanish Society of Anesthesiology, Resuscitation, and Pain Therapy (SEDAR), the Spanish Society of Emergency Medicine (SEMES), and the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC) present the Guide for the comprehensive management of difficult airway in adult patients. Its principles are focused on the human factors, cognitive processes for decision-making in critical situations, and optimization in the progression of strategies application to preserve adequate alveolar oxygenation in order to enhance safety and the quality of care. The document provides evidence-based recommendations, theoretical-educational tools, and implementation tools, mainly cognitive aids, applicable to airway management in the fields of anesthesiology, critical care, emergencies, and prehospital medicine. For this purpose, an extensive literature search was conducted following PRISMA-R guidelines and was analyzed using the GRADE methodology. Recommendations were formulated according to the GRADE methodology. Recommendations for sections with low-quality evidence were based on expert opinion through consensus reached via a Delphi questionnaire.

Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR), Spanish Society of Emergency and Emergency Medicine (SEMES) and Spanish Society of Otolaryngology, Head and Neck Surgery (SEORL-CCC) Guideline for difficult airway management. Part II.

The Airway Management section of the Spanish Society of Anesthesiology, Resuscitation, and Pain Therapy (SEDAR), the Spanish Society of Emergency Medicine (SEMES), and the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC) present the Guide for the comprehensive management of difficult airway in adult patients. Its principles are focused on the human factors, cognitive processes for decision-making in critical situations, and optimization in the progression of strategies application to preserve adequate alveolar oxygenation in order to enhance safety and the quality of care. The document provides evidence-based recommendations, theoretical-educational tools, and implementation tools, mainly cognitive aids, applicable to airway management in the fields of anesthesiology, critical care, emergencies, and prehospital medicine. For this purpose, an extensive literature search was conducted following PRISMA-R guidelines and was analyzed using the GRADE methodology. Recommendations were formulated according to the GRADE methodology. Recommendations for sections with low-quality evidence were based on expert opinion through consensus reached via a Delphi questionnaire.

Optical properties of ZnFe2O4 nanoparticles and Fe-decorated inversion domain boundaries in ZnO.

The maximum efficiency of solar cells utilizing a single layer for photovoltaic conversion is given by the single junction Shockley-Queisser limit. In tandem solar cells, a stack of materials with different band gaps contribute to the conversion, enabling tandem cells to exceed the single junction Shockley-Queisser limit. An intriguing variant of this approach is to embed semiconducting nanoparticles in a transparent conducting oxide (TCO) solar cell front contact. This alternative route would enhance the functionality of the TCO layer, allowing it to participate directly in photovoltaic conversion via photon absorption and charge carrier generation in the nanoparticles. Here, we demonstrate the functionalization of ZnO through incorporation of either ZnFe2O4 spinel nanoparticles (NPs) or inversion domain boundaries (IDBs) decorated by Fe. Diffuse reflectance spectroscopy and electron energy loss spectroscopy show that samples containing spinel particles and samples containing IDBs decorated by Fe both display enhanced absorption in the visible range at around 2.0 and 2.6 eV. This striking functional similarity was attributed to the local structural similarity around Fe-ions in spinel ZnFe2O4 and at Fe-decorated basal IDBs. Hence, functional properties of the ZnFe2O4 arise already for the two-dimensional basal IDBs, from which these planar defects behave like two-dimensional spinel-like inclusions in ZnO. Cathodoluminescence spectra reveal an increased luminescence around the band edge of spinel ZnFe2O4 when measuring on the spinel ZnFe2O4 NPs embedded in ZnO, whereas spectra from Fe-decorated IDBs could be deconvoluted into luminescence contributions from bulk ZnO and bulk ZnFe2O4.

Regulatory and metabolic adaptations in the nitrogen assimilation of marine picocyanobacteria.

Prochlorococcus and Synechococcus are the two most abundant photosynthetic organisms on Earth, with a strong influence on the biogeochemical carbon and nitrogen cycles. Early reports demonstrated the streamlining of regulatory mechanisms in nitrogen metabolism and the removal of genes not strictly essential. The availability of a large series of genomes, and the utilization of latest generation molecular techniques have allowed elucidating the main mechanisms developed by marine picocyanobacteria to adapt to the environments where they thrive, with a particular interest in the strains inhabiting oligotrophic oceans. Given that nitrogen is often limited in those environments, a series of studies have explored the strategies utilized by Prochlorococcus and Synechococcus to exploit the low concentrations of nitrogen-containing molecules available in large areas of the oceans. These strategies include the reduction in the GC and the cellular protein contents; the utilization of truncated proteins; a reduced average amount of N in the proteome; the development of metabolic mechanisms to perceive and utilize nanomolar nitrate concentrations; and the reduced responsiveness of key molecular regulatory systems such as NtcA to 2-oxoglutarate. These findings are in sharp contrast with the large body of knowledge obtained in freshwater cyanobacteria. We will outline the main discoveries, stressing their relevance to the ecological success of these important microorganisms.

A critical review of the perioperative fluid therapy and hemodynamic monitoring recommendations of the Enhanced Recovery of the Adult Pathway (RICA): A position statement of the fluid therapy and hemodynamic monitoring Subcommittee of the Hemostasis, Transfusion Medicine and Fluid Therapy Section (SHTF) of the Spanish Society of Anesthesiology and Critical Care (SEDAR).

In an effort to standardize perioperative management and improve postoperative outcomes of adult patients undergoing surgery, the Ministry of Health, through the Spanish Multimodal Rehabilitation Group (GERM), and the Aragonese Institute of Health Sciences, in collaboration with multiple Spanish scientific societies and based on the available evidence, published in 2021 the Spanish Intensified Adult Recovery (RICA) guideline. This document includes 12 perioperative measures related to fluid therapy and hemodynamic monitoring. Fluid administration and hemodynamic monitoring are not straightforward but are directly related to postoperative patient outcomes. The Fluid Therapy and Hemodynamic Monitoring Subcommittee of the Hemostasis, Transfusion Medicine and Fluid Therapy Section (SHTF) of the Spanish Society of Anesthesiology and Critical Care (SEDAR) has reviewed these recommendations and concluded that they should be revised as they do not follow an adequate methodology.

Research priorities in perioperative fluid therapy and hemodynamic monitoring: A Delphi Consensus Survey from the Fluid Therapy and Hemodynamic Monitoring Subcommittee of the Hemostasis, Transfusion Medicine and Fluid Therapy Section (SHTF) of the Spanish Society of Anesthesiology and Critical Care (SEDAR).

BACKGROUND: Research in fluid therapy and perioperative hemodynamic monitoring is difficult and expensive. The objectives of this study were to summarize these topics and to prioritize these topics in order of research importance. METHODS: Electronic structured Delphi questionnaire over three rounds among 30 experts in fluid therapy and hemodynamic monitoring identified through the Fluid Therapy and Hemodynamic Monitoring Subcommittee of the Hemostasis, Transfusion Medicine and Fluid Therapy Section of the Spanish Society of Anesthesiology and Critical Care. RESULTS: 77 topics were identified and ranked in order of prioritization. Topics were categorized into themes of crystalloids, colloids, hemodynamic monitoring and others. 31 topics were ranked as essential research priority. To determine whether intraoperative hemodynamic optimization algorithms based on the invasive or noninvasive Hypotension Prediction Index versus other management strategies could decrease the incidence of postoperative complications. As well as whether the use of renal stress biomarkers together with a goal-directed fluid therapy protocol could reduce hospital stay and the incidence of acute kidney injury in adult patients undergoing non-cardiac surgery, reached the highest consensus. CONCLUSIONS: The Fluid Therapy and Hemodynamic Monitoring Subcommittee of the Hemostasis, Transfusion Medicine and Fluid Therapy Section of the Spanish Society of Anesthesiology and Critical Care will use these results to carry out the research.

Human decidual stromal cells secrete C-X-C motif chemokine 13, express B cell-activating factor and rescue B lymphocytes from apoptosis: distinctive characteristics of follicular dendritic cells.

BACKGROUND: Decidual stromal cells (DSCs) have classically been considered fibroblastic cells, although their function, cell lineage and origin are not fully understood. We previously demonstrated that human DSCs showed similarities with follicular dendritic cells (FDCs): DSCs expressed FDC-associated antigens, both types of cells are contractile and both are related to mesenchymal stem cells (MSCs). To further characterize DSCs, we investigated whether DSCs and FDCs share any distinctive phenotypical and functional characteristics. METHODS: Human FDC lines were obtained from tonsillectomy samples, human DSC lines from elective termination of pregnancy samples and human MSC lines from bone marrow aspirates. We isolated DSC, FDC and MSC lines and compared their characteristics with flow cytometry and enzyme-linked immunosorbent assay. Cell lines were cultured with tumour necrosis factor (TNF) and lymphotoxin (LT)α(1)ß(2), cytokines involved in FDC differentiation. Cell lines were also differentiated in culture after exposure to progesterone and cAMP, factors involved in the differentiation (decidualization) of DSC. RESULTS: Like MSCs, DSCs and FDCs expressed MSC-associated antigens (CD10, CD29, CD54, CD73, CD106, α-smooth muscle actin and STRO-1) and lacked CD45 expression, and all three types of cell line showed increased expression of CD54 (ICAM-1) and CD106 (VCAM-1) when cultured TNF and LTα(1)ß(2). DSCs and FDCs, however, exhibited characteristics not observed in MSCs: DSCs expressed FDC-associated antigens CD14, CD21 and CD23, B cell-activating factor and secreted C-X-C motif chemokine 13. Moreover, DSC lines but not MSC lines inhibited the spontaneous apoptosis of B lymphocytes, a typical functional attribute of FDC. During culture with progesterone and cAMP, FDCs, like DSCs but in contrast to MSCs, changed their morphology from a fibroblastic to a rounder shape, and cells secreted prolactin. CONCLUSIONS: Our results suggest that DSCs and FDCs share a common precursor in MSCs but this precursor acquires new capacities when it homes to peripheral tissues. We discuss these shared properties in the context of immune-endocrine regulation during pregnancy.

Peripheral VA-ECMO left ventricular dysfunction: A combined biventricular assistance two case-report.

We report 2 patients with cardiogenic shock that developed severe left ventricular dysfunction due to a non-opening aortic valve while on peripheral VA-ECMO (Veno-Arterial Extracorporeal Membrane Oxygenator). Patients were managed combining a LV (Left Ventricle) mechanical assist device, and central VA - ECMO to support the right ventricle, thus providing full circulatory and respiratory assistance. Patients were able to bridge to cardiac transplantation. We therefore recommend such combination in patients with severe LV dysfunction while on p-ECMO (peripheral ECMO) support.

Peripheral VA-ECMO left ventricular dysfunction: A combined biventricular assistance two case-report. / Asistencia biventricular en el manejo de la disfunción ventricular izquierda secundaria a ECMO-VA periférica: a propósito de 2 casos.

We report 2patients with cardiogenic shock that developed severe left ventricular dysfunction due to a non-opening aortic valve while on peripheral VA-ECMO (Veno-Arterial Extracorporeal Membrane Oxygenator). Patients were managed combining a LV (Left Ventricle) mechanical assist device, and central VA - ECMO to support the right ventricle, thus providing full circulatory and respiratory assistance. Patients were able to bridge to cardiac transplantation. We therefore recommend such combination in patients with severe LV dysfunction while on p-ECMO (peripheral ECMO) support.

Summary of recommendations and key points of the consensus of Spanish scientific societies (SEPAR, SEMICYUC, SEMES; SECIP, SENEO, SEDAR, SENP) on the use of non-invasive ventilation and high-flow oxygen therapy with nasal cannulas in adult, pediatric, and neonatal patients with severe acute respiratory failure.

Non-invasive respiratory support (NIRS) in adult, pediatric, and neonatal patients with acute respiratory failure (ARF) comprises two treatment modalities, non-invasive mechanical ventilation (NIMV) and high-flow nasal cannula (HFNC) therapy. However, experts from different specialties disagree on the benefit of these techniques in different clinical settings. The objective of this consensus was to develop a series of good clinical practice recommendations for the application of non-invasive support in patients with ARF, endorsed by all scientific societies involved in the management of adult and pediatric/neonatal patients with ARF. To this end, the different societies involved were contacted, and they in turn appointed a group of 26 professionals with sufficient experience in the use of these techniques. Three face-to-face meetings were held to agree on recommendations (up to a total of 71) based on a literature review and the latest evidence associated with 3 categories: indications, monitoring and follow-up of NIRS. Finally, the experts from each scientific society involved voted telematically on each of the recommendations. To classify the degree of agreement, an analogue classification system was chosen that was easy and intuitive to use and that clearly stated whether the each NIRS intervention should be applied, could be applied, or should not be applied.