ARCHERY: a prospective observational study of artificial intelligence-based radiotherapy treatment planning for cervical, head and neck and prostate cancer - study protocol.

INTRODUCTION: Fifty per cent of patients with cancer require radiotherapy during their disease course, however, only 10%-40% of patients in low-income and middle-income countries (LMICs) have access to it. A shortfall in specialised workforce has been identified as the most significant barrier to expanding radiotherapy capacity. Artificial intelligence (AI)-based software has been developed to automate both the delineation of anatomical target structures and the definition of the position, size and shape of the radiation beams. Proposed advantages include improved treatment accuracy, as well as a reduction in the time (from weeks to minutes) and human resources needed to deliver radiotherapy. METHODS: ARCHERY is a non-randomised prospective study to evaluate the quality and economic impact of AI-based automated radiotherapy treatment planning for cervical, head and neck, and prostate cancers, which are endemic in LMICs, and for which radiotherapy is the primary curative treatment modality. The sample size of 990 patients (330 for each cancer type) has been calculated based on an estimated 95% treatment plan acceptability rate. Time and cost savings will be analysed as secondary outcome measures using the time-driven activity-based costing model. The 48-month study will take place in six public sector cancer hospitals in India (n=2), Jordan (n=1), Malaysia (n=1) and South Africa (n=2) to support implementation of the software in LMICs. ETHICS AND DISSEMINATION: The study has received ethical approval from University College London (UCL) and each of the six study sites. If the study objectives are met, the AI-based software will be offered as a not-for-profit web service to public sector state hospitals in LMICs to support expansion of high quality radiotherapy capacity, improving access to and affordability of this key modality of cancer cure and control. Public and policy engagement plans will involve patients as key partners.

Role of bilayer characteristics on the structural fate of aß(1-40) and aß(25-40).

The ß-amyloid (Aß) peptide is derived from the transmembrane (TM) helix of the amyloid precursor protein (APP) and has been shown to interact with membrane surfaces. To understand better the role of peptide-membrane interactions in cell death and ultimately in Alzheimer's disease, a better understanding of how membrane characteristics affect the binding, solvation, and secondary structure of Aß is needed. Employing a combination of circular dichroism and deep-UV resonance Raman spectroscopies, Aß(25-40) was found to fold spontaneously upon association with anionic lipid bilayers. The hydrophobic portion of the disease-related Aß(1-40) peptide, Aß(25-40), has often been used as a model for how its legacy TM region may behave structurally in aqueous solvents and during membrane encounters. The structure of the membrane-associated Aß(25-40) peptide was found to depend on both the hydrophobic thickness of the bilayer and the duration of incubation. Similarly, the disease-related Aß(1-40) peptide also spontaneously associates with anionic liposomes, where it initially adopts mixtures of disordered and helical structures. The partially disordered helical structures then convert to ß-sheet structures over longer time frames. ß-Sheet structure is formed prior to helical unwinding, implying a model in which ß-sheet structure, formed initially from disordered regions, prompts the unwinding and destabilization of membrane-stabilized helical structure. A model is proposed to describe the mechanism of escape of Aß(1-40) from the membrane surfaces following its formation by cleavage of APP within the membrane.

Evolution of quantitative methods in protein secondary structure determination via deep-ultraviolet resonance Raman spectroscopy.

Deep-ultraviolet resonance Raman (DUVRR) spectra is sensitive to secondary structural motifs but, similar to circular dichroism (CD) and infrared spectroscopy, requires the application of multivariate and advanced statistical analysis methods to resolve the pure secondary structure Raman spectra (PSSRS) for determination of secondary structure composition. Secondary structure motifs are selectively enhanced by different excitation wavelengths, a characteristic that inspired the first methods for quantifying secondary structures by DUVRR. This review traces the evolution of multivariate methods and their application to secondary structure composition analyses of proteins by DUVRR spectroscopy from the first experiments using two-wavelengths, and culminating with recent studies utilizing time-resolved DUVRR measurements.

Multivariate analysis of emission decay matrices for distinguishing ground state heterogeneity and excited state reactions of tryptophan.

The amino acid tryptophan displays emission solvatochromism, an emission maximum that shifts with solvent polarity, which is often used in protein studies to indicate local environment hydrophobicity. Use of tryptophan solvatochromism in time-resolved protein studies has traditionally been complicated due to the undescribed photokinetics that result in a characteristic multiexponential emission decay. For the first time, by application of the photokinetic matrix decomposition (PMD) multivariate curve resolution method to time-resolved emission decay (TRED) data, a distinguishment between ground state heterogeneous (GSH) and excited state reaction (ESR) type photokinetics of tryptophan in solution is made possible. It is found that molecular tryptophan displays two emission spectra that decay independently, suggesting GSH type photokinetics, one at 347 nm with a lifetime of 0.5 ns and one at 363 nm with a lifetime of 3.1 ns. When tryptophan is incorporated into a peptide, mastoparan X, the data similarly contain two emission spectra that decay independently, but are shifted in wavelength. Photobleaching experiments confirm that the PMD method is sensitive to tryptophan emission quenching, and therefore may be applied to determine the photokinetics of tryptophan that occur in proteins. Future applications of PMD analysis of tryptophan TRED data as a bioanalytical tool for further characterizing dynamic protein processes are discussed.

Numerical correction of detector channel cross-talk using full-spectrum fluorescence correlation spectroscopy.

Fluorescence correlation spectroscopy (FCS) uses fluctuations in the fluorescence collected from a small illuminated volume to measure dynamic processes of fluorophores. In traditional FCS, spectral overlap produces cross-talk in dedicated detector channels, undermining the accuracy of measurements of molecular interactions. Here, the experimental realization of full-spectrum fluorescence correlation spectroscopy is described and coupled with multivariate data analysis to numerically correct detector cross-talk, isolating spectra and fluctuation traces of mixture components in spite of overlap. Application of this methodology is illustrated using the measurement of the diffusion constant of labeled polystyrene in hydroxypropyl cellulose in the presence of a persistent dye. Additionally, the results show that full-spectrum FCS with multivariate analysis can isolate and characterize signals from unanticipated sample components.

Hispanic parents' perspective on early PACU visitation.

Many reports indicate that family member presence in the PACU may decrease anxiety levels in both patients and family members. PACUs, nevertheless, often restrict family visitation because of the close proximity to ORs, complexity, and the fast-paced recovery environment. The purpose of this study was to determine the effect of parental presence on the anxiety levels of children ages 9 to 18, observed behavior of children ages 6 to 8, and reported parental anxiety in the pre- and postoperative periods. The quasi-experimental design used a sample of 72 parent-patient dyads, predominately Hispanic, who completed either the pediatric (9-12) or teenager/adult Speilberger State Anxiety forms. Forty (40) parents were placed in the PACU with their children, and 32 remained in the Waiting Room. PACU nurses coded observations of parents and observations of patients aged 6 to 8 years. FLACC or numeric pain scales scores were also collected. Results showed no difference in parental anxiety between those who were placed in the PACU or Waiting Room. Patients aged 13 to 18 with parents in-PACU had significantly lowered anxiety scores than patients with parents in-Waiting Room (t = 2.51, P = .02). Anxiety scores for younger children (9-12 years old) were not lowered postoperatively regardless of parent placement. Regardless of age, patients with parents in-PACU showed statistically significantly greater pain pre-operatively compared with patients with in-Waiting Room parents (t = 3.15, P = .002), but this difference disappeared postoperatively.

Moderate sedation for echocardiography of preschoolers.

Preschoolers frequently require sedation for echocardiograms. This study compared various sedation drugs at the authors' institution, as well as the charges for moderate versus deep sedation. From 2001 to 2007, sedation was administered to 703 patients ages 2 to 4 years. Four drug regimens were used: chloral hydrate (CH), chloral hydrate with diphenhydramine (CH + D), chloral hydrate with hydroxyzine hydrochloride (CH + H), and midazolam. The mean onset of sedation was 37 min, and the mean duration of sedation was 47 min. The CH group fell asleep the most quickly (30 min; p < 0.001), and the CH + D patients experienced the most prolonged sedations (13%; p < 0.001). Studies were completed by 97% of the chloral hydrate group, 98% of the CH + D group, and 94% of the CH + H group compared with 66% of the midazolam group (p < 0.001). Complications (7.4%) were minor and not significant for any particular medication. The charges for moderate sedation averaged $709 compared with $3,628 for deep sedation. The findings demonstrated that chloral hydrate was the fastest-acting agent and had a high success rate with minimally prolonged sedations. The low complication rate for chloral hydrate, and the much lower cost for its use to induce moderate sedation have made chloral hydrate our preference for the echocardiographic sedation of preschoolers.

Spectral heterogeneity of PRODAN fluorescence in isotropic solvents revealed by multivariate photokinetic analysis.

This paper describes a multivariate analysis of the fluorescence emission of 6-propionyl-2-dimethylaminonaphthalene (PRODAN) in a series of isotropic solvents of differing polarity and hydrogen-bonding ability. Multivariate methods distill the essential features from spectral data matrices so that the structural details that are embedded within the data are revealed to the analyst. In the aprotic solvents investigated, the analysis reveals a pair of emission components that have emission maxima that scale with the orientational polarizability. In the alcohols, short-lived, polarity-independent blue bands tentatively attributed to neutral hydrogen-bonded solute-solvent complexes form and relax prior to emission from paired bands that have Stokes shifts that scale with the solvent hydrogen-bonding ability rather than the polarity. In water, the short-lived blue bands were not observed, but the shift in the paired bands did scale with the solvent hydrogen-bonding ability.

Focus on clinical best practices, patient safety and operational efficiency.

Moving from a paper-based medication management environment to completely on-line processes was a major change for nurses--the largest group of employees and, ultimately, MOE/MAR users. Nursing's involvement and their experiences are analyzed.