Proactive and integrated consultation-liaison psychiatry for older medical inpatients: A mixed methods description of training, care provided and clinician experience in the HOME study.

OBJECTIVES: To describe the practical experience of delivering a proactive and integrated consultation-liaison (C-L) psychiatry service model (PICLP). PICLP is designed for older medical inpatients and is explicitly biopsychosocial and discharge-focused. In this paper we report: (a) observations on the training of 15 clinicians (seven senior C-L psychiatrists and eight assisting clinicians) to deliver PICLP; (b) the care they provided to 1359 patients; (c) their experiences of working in this new way. METHOD: A mixed methods observational study using quantitative and qualitative data, collected prospectively over two years as part of The HOME Study (a randomized trial comparing PICLP with usual care). RESULTS: The clinicians were successfully trained to deliver PICLP according to the service manual. They proactively assessed all patients and found that most had multiple biopsychosocial problems impeding their timely discharge from hospital. They integrated with ward teams to provide a range of interventions aimed at addressing these problems. Delivering PICLP took a modest amount of clinical time, and the clinicians experienced it as both clinically valuable and professionally rewarding. CONCLUSION: The experience of delivering PICLP highlights the special role that C-L psychiatry clinicians, working in a proactive and integrated way, can play in medical care.

Production, isolation, and shipment of clinically relevant quantities of astatine-211: A simple and efficient approach to increasing supply.

The alpha emitter astatine-211 (211At) is a promising candidate for cancer treatment based on Targeted Alpha (α) Therapy (TAT). A small number of facilities, distributed across the United States, are capable of accelerating α-particle beams to produce 211At. However, challenges remain regarding strategic methods for shipping 211At in a form adaptable to advanced radiochemistry reactions and other uses of the radioisotope. PURPOSE: Our method allows shipment of 211At in various quantities in a form convenient for further radiochemistry. PROCEDURES: For this study, a 3-octanone impregnated Amberchrom CG300M resin bed in a column cartridge was used to separate 211At from the bismuth matrix on site at the production accelerator (Texas A&M) in preparation for shipping. Aliquots of 6 M HNO3 containing up to ≈2.22 GBq of 211At from the dissolved target were successfully loaded and retained on columns. Exempt packages (<370 MBq) were shipped to a destination radiochemistry facility, University of Texas MD Anderson Cancer Center, in the form of a convenient air-dried column. Type A packages have been shipped overnight to University of Alabama at Birmingham. MAIN FINDINGS: Air-dried column hold times of various lengths did not inhibit simple and efficient recovery of 211At. Solution eluted from the column was sufficiently high in specific activity to successfully radiolabel a model compound, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1), with 211At. The method to prepare and ship 211At described in this manuscript has also been used to ship larger quantities of 211At a greater distance to University of Alabama at Birmingham. PRINCIPAL CONCLUSIONS: The successful proof of this method paves the way for the distribution of 211At from Texas A&M University to research institutions and clinical oncology centers in Texas and elsewhere. Use of this simple method at other facilities has the potential increase the overall availability of 211At for preclinical and clinical studies.

Clinical characteristics of people presenting with first episode psychosis pre- and during the COVID-19 pandemic in KwaZulu-Natal Province, South Africa.

BACKGROUND: The COVID-19 pandemic and the lockdown experience may have not only precipitated or exacerbated mental illness but also influenced access to care and the nature and content of the psychotic symptomatology of people with psychosis. AIM: This study aimed to evaluate the association of the COVID-19 pandemic and lockdown experience on clinical presentation and quality of life of people (QOL) with first episode psychosis (FEP). METHOD: Two first episode psychosis cohorts from the same epidemiological area collected prior to, and during the COVID-19 pandemic and lockdown were compared in terms of clinical symptomatology, substance use and QOL. All adult in- and outpatients with FEP at five clinical units in KwaZulu-Natal, South Africa, aged between 18 and 45 years, were assessed with the MINI interview for psychosis, Positive and Negative Symptoms Scale, WHO Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) and the WHO QOL scales. RESULTS: Eighty-eight FEP participants were recruited between 2019 and 2020 (cohort 1) before the pandemic. Study recruitment was suspended in March 2020 due to the pandemic. On study resumption from November 2020 to November 2022, 95 new participants (cohort 2) were recruited. There were no sociodemographic differences between the two cohorts, except unemployment status (57% vs. 65%) and household income. The cohort presenting post-COVID-19 pandemic onset had significantly more positive psychotic symptoms (21.9 vs. 23.7), lower PANSS domain depressive score, more lifetime use of tobacco, cannabis and alcohol. However, they reported improved QOL (196 vs. 239). CONCLUSION: Following the pandemic and lockdown experience participants presented with more severe psychotic symptoms and concomitant substance use but improved perceived QOL. This suggests the need to explore individual and social factors that may influence the clinical presentation.

Creating complex protocells and prototissues using simple DNA building blocks.

Building synthetic protocells and prototissues hinges on the formation of biomimetic skeletal frameworks. Recreating the complexity of cytoskeletal and exoskeletal fibers, with their widely varying dimensions, cellular locations and functions, represents a major material hurdle and intellectual challenge which is compounded by the additional demand of using simple building blocks to ease fabrication and control. Here we harness simplicity to create complexity by assembling structural frameworks from subunits that can support membrane-based protocells and prototissues. We show that five oligonucleotides can anneal into nanotubes or fibers whose tunable thicknesses and lengths spans four orders of magnitude. We demonstrate that the assemblies' location inside protocells is controllable to enhance their mechanical, functional and osmolar stability. Furthermore, the macrostructures can coat the outside of protocells to mimic exoskeletons and support the formation of millimeter-scale prototissues. Our strategy could be exploited in the bottom-up design of synthetic cells and tissues, to the generation of smart material devices in medicine.

Cannabis use and psychotic disorders in diverse settings in the Global South: findings from INTREPID II.

BACKGROUND: Cannabis use has been linked to psychotic disorders but this association has been primarily observed in the Global North. This study investigates patterns of cannabis use and associations with psychoses in three Global South (regions within Latin America, Asia, Africa and Oceania) settings. METHODS: Case-control study within the International Programme of Research on Psychotic Disorders (INTREPID) II conducted between May 2018 and September 2020. In each setting, we recruited over 200 individuals with an untreated psychosis and individually-matched controls (Kancheepuram India; Ibadan, Nigeria; northern Trinidad). Controls, with no past or current psychotic disorder, were individually-matched to cases by 5-year age group, sex and neighbourhood. Presence of psychotic disorder assessed using the Schedules for Clinical Assessment in Neuropsychiatry and cannabis exposure measured by the World Health Organisation Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). RESULTS: Cases reported higher lifetime and frequent cannabis use than controls in each setting. In Trinidad, cannabis use was associated with increased odds of psychotic disorder: lifetime cannabis use (adj. OR 1.58, 95% CI 0.99-2.53); frequent cannabis use (adj. OR 1.99, 95% CI 1.10-3.60); cannabis dependency (as measured by high ASSIST score) (adj. OR 4.70, 95% CI 1.77-12.47), early age of first use (adj. OR 1.83, 95% CI 1.03-3.27). Cannabis use in the other two settings was too rare to examine associations. CONCLUSIONS: In line with previous studies, we found associations between cannabis use and the occurrence and age of onset of psychoses in Trinidad. These findings have implications for strategies for prevention of psychosis.

Water, sanitation and depression in rural communities: evidence from nationally representative study data in South Africa.

Clean water and sanitation provisions are essential for good hygiene and health, with rural South Africa facing a simultaneous access crisis of both, the direct health effect of restricted access to both on mental health remaining scarce and largely overlooked. This study investigated the association between access to clean water and sanitation on depression in rural South Africa utilizing the most recent data (year 2017) from the South African National Income Dynamics Study. Our study outcome was depression, based on the 10-item abridged version of the Center for Epidemiologic Studies Depression Scale (data available in SA-NIDS), the main exposures being access to clean water and adequate sanitation facilities (i.e. flushing toilets). Two types of analyses were conducted: first, adjusted logistic regression models were fitted to assess the relationship between lack of access to clean water and adequate sanitation to depression. Second, we conducted mediation analysis to investigate whether access to clean water mediated the relationship between lack of access to toilets and depression. A high proportion of rural participants lacked access to clean water (n = 6,188, 47.6%) and adequate toilets (n = 9,797, 81.6%). The regression analyses indicated that lack of access to both clean water (OR = 1.21, 95% CI: 1.06-1.39) and adequate sanitation (OR = 1.36, 95% CI: 1.10-1.69) were significantly associated with greater odds of depression. The mediation analysis indicated that access to clean water partially mediated the relationship between lack of access to adequate sanitation and depression, the total mediated effect being 18.2% (95% CI: 11.0%-51.0%). Most rural communities in South Africa lack access to basic services that are essential for human dignity and a decent quality of life, leading to opportunities for poor mental health, with its various consequences for socio-economic development and personal wellbeing, including avoidable depression.

Urbanicity and rates of untreated psychotic disorders in three diverse settings in the Global South.

BACKGROUND: Extensive evidence indicates that rates of psychotic disorder are elevated in more urban compared with less urban areas, but this evidence largely originates from Northern Europe. It is unclear whether the same association holds globally. This study examined the association between urban residence and rates of psychotic disorder in catchment areas in India (Kancheepuram, Tamil Nadu), Nigeria (Ibadan, Oyo), and Northern Trinidad. METHODS: Comprehensive case detection systems were developed based on extensive pilot work to identify individuals aged 18-64 with previously untreated psychotic disorders residing in each catchment area (May 2018-April/May/July 2020). Area of residence and basic demographic details were collected for eligible cases. We compared rates of psychotic disorder in the more v. less urban administrative areas within each catchment area, based on all cases detected, and repeated these analyses while restricting to recent onset cases (<2 years/<5 years). RESULTS: We found evidence of higher overall rates of psychosis in more urban areas within the Trinidadian catchment area (IRR: 3.24, 95% CI 2.68-3.91), an inverse association in the Nigerian catchment area (IRR: 0.68, 95% CI 0.51-0.91) and no association in the Indian catchment area (IRR: 1.18, 95% CI 0.93-1.52). When restricting to recent onset cases, we found a modest positive association in the Indian catchment area. CONCLUSIONS: This study suggests that urbanicity is associated with higher rates of psychotic disorder in some but not all contexts outside of Northern Europe. Future studies should test candidate mechanisms that may underlie the associations observed, such as exposure to violence.

Epidemiology of Untreated Psychoses in 3 Diverse Settings in the Global South: The International Research Program on Psychotic Disorders in Diverse Settings (INTREPID II).

Importance: Less than 10% of research on psychotic disorders has been conducted in settings in the Global South, which refers broadly to the regions of Latin America, Asia, Africa, and Oceania. There is a lack of basic epidemiological data on the distribution of and risks for psychoses that can inform the development of services in many parts of the world. Objective: To compare demographic and clinical profiles of cohorts of cases and rates of untreated psychoses (proxy for incidence) across and within 3 economically and socially diverse settings in the Global South. Two hypotheses were tested: (1) demographic and clinical profiles of cases with an untreated psychotic disorder vary across setting and (2) rates of untreated psychotic disorders vary across and within setting by clinical and demographic group. Design, Setting, and Participants: The International Research Program on Psychotic Disorders in Diverse Settings (INTREPID II) comprises incidence, case-control, and cohort studies of untreated psychoses in catchment areas in 3 countries in the Global South: Kancheepuram District, India; Ibadan, Nigeria; and northern Trinidad. Participants were individuals with an untreated psychotic disorder. This incidence study was conducted from May 1, 2018, to July 31, 2020. In each setting, comprehensive systems were implemented to identify and assess all individuals with an untreated psychosis during a 2-year period. Data were analyzed from January 1 to May 1, 2022. Main Outcomes and Measures: The presence of an untreated psychotic disorder, assessed using the Schedules for Clinical Assessment in Neuropsychiatry, which incorporate the Present State Examination. Results: Identified were a total of 1038 cases, including 64 through leakage studies (Kancheepuram: 268; median [IQR] age, 42 [33-50] years; 154 women [57.5%]; 114 men [42.5%]; Ibadan: 196; median [IQR] age, 34 [26-41] years; 93 women [47.4%]; 103 men [52.6%]; Trinidad: 574; median [IQR] age, 30 [23-40] years; 235 women [40.9%]; 339 men [59.1%]). Marked variations were found across and within settings in the sex, age, and clinical profiles of cases (eg, lower percentage of men, older age at onset, longer duration of psychosis, and lower percentage of affective psychosis in Kancheepuram compared with Ibadan and Trinidad) and in rates of untreated psychosis. Age- and sex-standardized rates of untreated psychoses were approximately 3 times higher in Trinidad (59.1/100 000 person-years; 95% CI, 54.2-64.0) compared with Kancheepuram (20.7/100 000 person-years; 95% CI, 18.2-23.2) and Ibadan (14.4/100 000 person-years; 95% CI, 12.3-16.5). In Trinidad, rates were approximately 2 times higher in the African Trinidadian population (85.4/100 000 person-years; 95% CI, 76.0-94.9) compared with the Indian Trinidadian (43.9/100 000 person-years; 95% CI, 35.7-52.2) and mixed populations (50.7/100 000 person-years; 95% CI, 42.0-59.5). Conclusions and Relevance: This analysis adds to research that suggests that core aspects of psychosis vary by historic, economic, and social context, with far-reaching implications for understanding and treatment of psychoses globally.

Developing and testing unconditional cash transfer strategies among young adults with first-episode psychosis in South Africa: a study protocol for a pilot randomised control trial (PRS-FEP trial).

INTRODUCTION: Access to mental health services is a challenge, especially for young people who are over-represented in the unemployment and poverty index in South Africa. Therefore, continuing care is a problem after hospital discharge for young people with first-episode psychosis (FEP) due to a lack of clinical engagement and follow-up, for which they need support, including financial, to improve their outcomes. This pilot randomised control trial (RCT) aims to assess the feasibility and acceptability of financial support, in the form of an unconditional cash transfer (UCT), among young patients with FEP to prevent relapse. METHODS AND ANALYSIS: This study will use a 1:1 ratio two-arm open-label pilot RCT of 60 young participants (18-29 years) with FEP in remission, who will be recruited from specialised psychiatric facilities in KwaZulu-Natal Province, South Africa. This study will implement an UCT and assess its feasibility, acceptability and preliminary clinical outcomes (ie, medication adherence, relapse, quality of life, personal and social function). The follow-up time will be 3 months, the outcomes being measured at baseline, months 1 and 3. Descriptive and conventional content analysis will be done for quantitative and qualitative data, respectively. ETHICS AND DISSEMINATION: The study obtained provisional approval from the Biomedical Research Ethics Committee at the University of KwaZulu-Natal(#BREC/00004117/2022). Also is registered on the South African National clinical trial registry (#DOH-27-092022-5894) and approved by the KwaZulu-Natal department of health (#NHRD Ref: KZ_2002209_033). The results from this investigation will be actively disseminated through peer-reviewed journal publications, conference presentations and stakeholder engagement. TRIAL REGISTRATION NUMBER: DOH-27-092022-5894.

Course of psychotic experiences and disorders among apprentice traditional health practitioners in rural South Africa: 3-year follow-up study.

Background: Culture is inevitably linked with the experience, interpretation and course of what modern biomedicine understands to be psychotic symptoms. However, data on psychoses in low- and middle-income countries are sparse. Our previous study showed that psychotic and mood-related experiences, symptoms and disorders are common among individuals who had received the ancestral calling to become a traditional health practitioner (THP) in rural KwaZulu-Natal, South Africa. Our related ethnographic study suggested that ukuthwasa (the training to become a THP) may positively moderate these calling-related symptoms. As far as we know, no research has been conducted into the course of psychiatric symptoms among apprentice THPs. Objective: We studied the course of psychotic experiences, symptoms and disorders among apprentice THPs. We also assessed their level of functioning and expanded our knowledge on ukuthwasa. Materials and methods: We performed a 3-year follow-up of a baseline sample of apprentice THPs (n = 48). Psychiatric assessments (CAPE, SCAN), assessment of functioning (WHODAS) and a semi-structured qualitative questionnaire were completed for 42 individuals. Results: At 3-year follow-up, psychotic experiences were associated with significantly less distress and there was a reduction in frequency of psychotic symptoms compared to baseline. The number of participants with psychotic disorders had decreased from 7 (17%) to 4 (10%). Six out of seven participants (86%) with a psychotic disorder at baseline no longer had a psychiatric diagnosis at follow-up. Although the mean level of disability among the (apprentice) THPs corresponded with the 78th percentile found in the general population, 37 participants (88%) reported no or mild disability. Forty-one participants (98%) reported that ukuthwasa had positively influenced their psychiatric symptoms. Conclusion: In rural KwaZulu-Natal, psychotic experiences, symptoms and disorders have a benign course in most individuals who are undergoing the process of becoming a THP. Ukuthwasa may be an effective, culturally sanctioned, healing intervention for some selected individuals, potentially because it reframes distressing experiences into positive and highly valued experiences, reduces stigma, and enhances social empowerment and identity construction. This implies that cultural and spiritual interventions can have a positive influence on the course of psychosis.

Early detection and treatment of acute illness in medical patients with novel software: a prospective quality improvement initiative.

OBJECTIVE: An ageing population and rising healthcare costs place healthcare systems at risk of failure. Our goal was to develop a technology that would identify illness early, initiate action and therein improve patient care, outcomes and save healthcare resources. DESIGN: This was a prospective interventional quality improvement study. SETTING: A 40 bed medical floor in a 300 bed Canadian tertiary care regional referral hospital. PARTICIPANTS: General ward patients randomly assigned to control or treatment groups. There was no cross-over or loss to follow-up. INTERVENTION: We designed an algorithm and software programme capable of detecting the sentinel change in a deteriorating patient's clinical condition and once detected direct early investigation and care. Study duration was 1 year. MAIN OUTCOME MEASURES: Primary outcome was patient transfer from the general medical ward to the intensive care unit (ICU). The secondary outcome was the time needed to (1) order investigations (2) contact senior medical staff and (3) senior medical staff intervention. RESULTS: We identified a decrease in the transfer of patients from the medical ward to the ICU. Over the course of the study including 273 patients (110 in the control group and 163 in the treatment group), transfers dropped from 14 to 3 with a relative risk reduction of 85.54% (95% CI 84.96 to 86.1), a number needed to treat of 9.19 (95% CI 9.01 to 9.36) and a absolute risk reduction of 10.89% (95% CI 10.7 to 11.1). We also found a statistically significant reduction in the time required to order investigations (p=0.049), contact senior medical staff (p=0.040) and senior medical staff intervention (p=0.045). CONCLUSION: A novel algorithm and software in the hands of nursing staff identified acute illness with adequate sensitivity and specificity to dramatically reduce ICU transfers and time to clinical intervention on a medical ward.

Complexation of Astatine(III) with Ketones: Roles of NO3- Counterion and Exploration of Possible Binding Modes.

Ketones have been proven effective in extracting astatine(III) from aqueous solvents. Previous theoretical studies suggested a mechanism where the "sp2" lone pair on the carbonyl oxygen donates electron density into the π system of the AtO+ molecular cation to form a dative-type bond. In this study, co-extraction of NO3- as AtO(NO3)·(O═CR1R2) species into the organic phase appears to be a key factor. Adjusting the electronic properties of the ketone, by having an aryl group instead of an alkyl group in the alpha position of the ketone, increased the electron density on C═O, increased the bond strength between the ketone and AtO+, and in turn increased the extraction of 211At into the organic phase. Extraction with diketones shows dependence on the bridging distance between the two carbonyl moieties, where a C3 or longer bridge results in a 10-fold increase in extraction into the organic phase. DFT calculations show the longer bridge allows for the chelation of AtO(NO3) by either the second carbonyl or the phenyl ring.

Sizing up DNA nanostructure assembly with native mass spectrometry and ion mobility.

Recent interest in biological and synthetic DNA nanostructures has highlighted the need for methods to comprehensively characterize intermediates and end products of multimeric DNA assembly. Here we use native mass spectrometry in combination with ion mobility to determine the mass, charge state and collision cross section of noncovalent DNA assemblies, and thereby elucidate their structural composition, oligomeric state, overall size and shape. We showcase the approach with a prototypical six-subunit DNA nanostructure to reveal how its assembly is governed by the ionic strength of the buffer, as well as how the mass and mobility of heterogeneous species can be well resolved by careful tuning of instrumental parameters. We find that the assembly of the hexameric, barrel-shaped complex is guided by positive cooperativity, while previously undetected higher-order 12- and 18-mer assemblies are assigned to defined larger-diameter geometric structures. Guided by our insight, ion mobility-mass spectrometry is poised to make significant contributions to understanding the formation and structural diversity of natural and synthetic oligonucleotide assemblies relevant in science and technology.

Community disaster exposure and first onset of depression: A panel analysis of nationally representative South African data, 2008-2017.

Sub-Saharan Africa faces unprecedented disasters, with climate change expected to exacerbate the frequency and severity of unpredictable and stressful catastrophic events. Unlike developed nations, reconstruction in developing nations is hindered by resource constraints, with certain communities potentially experiencing multiple and enduring effects of disasters. Despite the potential danger of such cumulative community disaster exposure on mental health (e.g. depression), large-scale population-level evidence for the region is limited. We investigated the association between exposure to cumulative disaster and the first onset of depression in a nationally representative survey in South Africa. We used panel data from the South African National Income Dynamics Study (SA-NIDS) from 2008-2017, consisting of 17,255 adult study participants who were depression free at baseline. Risk of first depression onset between individuals exposed and unexposed to community disaster was measured, accounting for multiple disaster exposure over time by fitting generalized estimating equation (GEE) regression models. Data on the geographic location of disasters were obtained from the South African government gazette, and mapped with the government delineated SA-NIDS households' locations. Of the sampled individuals, 2,986 were exposed to disaster during the study duration (17.3%). Increased cumulative community disaster was significantly associated with the likelihood of depression onset (adjusted relative risk [aRR] = 1.20, p<0.01, 95% CI: 1.09-1.33), even after controlling for socio-demographic factors. In sub-group analyses, greater likelihood of depression onset was found among females [but not in men] (aRR = 1.23, p<0.01, 95% CI: 1.09-1.38), Black African [but not in other population group] (aRR = 1.21, p<0.01, 95% CI: 1.09-1.36), lower education attainment group [but not in tertiary and above educational attainment group] (aRR = 1.20, p<0.01, 95% CI: 1.08-1.33), and lower income attainment group [but not in the top income quartile group] (aRR = 1.24, p<0.01, 95% CI: 1.11-1.38), due to cumulative community disaster. Although cumulative community disaster exposure was significantly associated with the first onset of depression, its negative impact may be more pronounced among individuals considered chronically socially vulnerable (i.e. the groups above) in South Africa. Given that many individuals in South Africa rely on social, food parcel relief, and health services from government/public sector, timely access to community-based supportive intervention is needed for disaster survivors, prioritizing socially vulnerable groups to help mitigate problems associated with mental health challenges.

Principles of Small-Molecule Transport through Synthetic Nanopores.

Synthetic nanopores made from DNA replicate the key biological processes of transporting molecular cargo across lipid bilayers. Understanding transport across the confined lumen of the nanopores is of fundamental interest and of relevance to their rational design for biotechnological applications. Here we reveal the transport principles of organic molecules through DNA nanopores by synergistically combining experiments and computer simulations. Using a highly parallel nanostructured platform, we synchronously measure the kinetic flux across hundreds of individual pores to obtain rate constants. The single-channel transport kinetics are close to the theoretical maximum, while selectivity is determined by the interplay of cargo charge and size, the pores' sterics and electrostatics, and the composition of the surrounding lipid bilayer. The narrow distribution of transport rates implies a high structural homogeneity of DNA nanopores. The molecular passageway through the nanopore is elucidated via coarse-grained constant-velocity steered molecular dynamics simulations. The ensemble simulations pinpoint with high resolution and statistical validity the selectivity filter within the channel lumen and determine the energetic factors governing transport. Our findings on these synthetic pores' structure-function relationship will serve to guide their rational engineering to tailor transport selectivity for cell biological research, sensing, and drug delivery.

Convolutional Neural Networks for Challenges in Automated Nuclide Identification.

Improvements in Radio-Isotope IDentification (RIID) algorithms have seen a resurgence in interest with the increased accessibility of machine learning models. Convolutional Neural Network (CNN)-based models have been developed to identify arbitrary mixtures of unstable nuclides from gamma spectra. In service of this, methods for the simulation and pre-processing of training data were also developed. The implementation of 1D multi-class, multi-label CNNs demonstrated good generalisation to real spectra with poor statistics and significant gain shifts. It is also shown that even basic CNN architectures prove reliable for RIID under the challenging conditions of heavy shielding and close source geometries, and may be extended to generalised solutions for pragmatic RIID.

Spectroscopic characterization of neptunium(VI), plutonium(VI), americium(VI) and neptunium(V) encapsulated in uranyl nitrate hexahydrate.

The coordination of crystalline products resulting from the co-crystallization of Np(vi), Pu(vi), Am(vi), and Np(v) with uranyl nitrate hexahydrate (UNH) has been revealed through solid-state spectroscopic characterization via diffuse reflectance UV-Vis-NIR spectroscopy, SEM-EDS, and extended X-ray absorption fine structure (EXAFS) spectroscopy. Density functional and multireference wavefunction calculations were performed to analyze the An(vi/v)O2(NO3)2·2H2O electronic structures and to help assign the observed transitions in the absorption spectra. EXAFS show a similar coordination between the U(VI) in UNH and Np(vi) and Pu(vi); while Am resulted in a similar coordination to Am(iii), as reduction of Am(vi) occurred prior to EXAFS data being obtained. The co-crystallization of the oxidized transuranic species-penta- and hexavalent-with UNH, represents a significant advance from not only a practical standpoint in providing an elegant solution for used nuclear fuel recycle, but also as an avenue to expand the fundamental understanding of the 5f electronic behavior in the solid-state.

Introducing Bacteria and Synthetic Biomolecules along Engineered DNA Fibers.

Deoxyribonucleic acid (DNA) nanotechnology enables user-defined structures to be built with unrivalled control. The approach is currently restricted across the nanoscale, yet the ability to generate macroscopic DNA structures has enormous potential with applications spanning material, physical, and biological science. To address this need, I employed DNA nanotechnology and developed a new macromolecular nanoarchitectonic assembly method to produce DNA fibers with customizable properties. The process involves coalescing DNA nanotubes under high salt conditions to yield filament superstructures. Using this strategy, fibers over 100 microns long, with stiffnesses 10 times greater than cytoskeletal actin filaments can be fabricated. The DNA framework enables fibers to be functionalized with advanced synthetic molecules, including, aptamers, origami, nanoparticles, and vesicles. In addition, the fibers can act as bacterial extracellular scaffolds and adhere Escherichia coli cells in a controllable fashion. These results showcase the opportunities offered from DNA nanotechnology across the macroscopic scale. The new biophysical approach should find widespread use, from the generation of hybrid-fabric materials, smart analytical devices in biomedicine, and platforms to study cell-cell interactions.

Hydrophobic Interactions between DNA Duplexes and Synthetic and Biological Membranes.

Equipping DNA with hydrophobic anchors enables targeted interaction with lipid bilayers for applications in biophysics, cell biology, and synthetic biology. Understanding DNA-membrane interactions is crucial for rationally designing functional DNA. Here we study the interactions of hydrophobically tagged DNA with synthetic and cell membranes using a combination of experiments and atomistic molecular dynamics (MD) simulations. The DNA duplexes are rendered hydrophobic by conjugation to a terminal cholesterol anchor or by chemical synthesis of a charge-neutralized alkyl-phosphorothioate (PPT) belt. Cholesterol-DNA tethers to lipid vesicles of different lipid compositions and charges, while PPT DNA binding strongly depends on alkyl length, belt position, and headgroup charge. Divalent cations in the buffer can also influence binding. Our MD simulations directly reveal the complex structure and energetics of PPT DNA within a lipid membrane, demonstrating that longer alkyl-PPT chains provide the most stable membrane anchoring but may disrupt DNA base paring in solution. When tested on cells, cholesterol-DNA is homogeneously distributed on the cell surface, while alkyl-PPT DNA accumulates in clustered structures on the plasma membrane. DNA tethered to the outside of the cell membrane is distinguished from DNA spanning the membrane by nuclease and sphingomyelinase digestion assays. The gained fundamental insight on DNA-bilayer interactions will guide the rational design of membrane-targeting nanostructures.

DNA Nanodevices with Selective Immune Cell Interaction and Function.

DNA nanotechnology produces precision nanostructures of defined chemistry. Expanding their use in biomedicine requires designed biomolecular interaction and function. Of topical interest are DNA nanostructures that function as vaccines with potential advantages over nonstructured nucleic acids in terms of serum stability and selective interaction with human immune cells. Here, we describe how compact DNA nanobarrels bind with a 400-fold selectivity via membrane anchors to white blood immune cells over erythrocytes, without affecting cell viability. The selectivity is based on the preference of the cholesterol lipid anchor for the more fluid immune cell membranes compared to the lower membrane fluidity of erythrocytes. Compacting DNA into the nanostructures gives rise to increased serum stability. The DNA barrels furthermore functionally modulate white blood cells by suppressing the immune response to pro-inflammatory endotoxin lipopolysaccharide. This is likely due to electrostatic or steric blocking of toll-like receptors on white blood cells. Our findings on immune cell-specific DNA nanostructures may be applied for vaccine development, immunomodulatory therapy to suppress septic shock, or the targeting of bioactive substances to immune cells.