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Poor iron status is one of the most prevalent problems facing infants worldwide, in both developing and developed countries(1). A complex interplay of both dietary and non-dietary factors affects iron intake, absorption, and requirements, and subsequently iron status(2). We aimed to describe iron status in an ethnically diverse cohort of urban-dwelling infants. Data were collected from 364 infants aged 7.0 to 10.0 months living in two main urban centres in New Zealand (Auckland and Dunedin) between July 2020 and February 2022. Participants were grouped by total ethnicity, with any participants who did not identify as either Māori or Pacific categorised into a single ‘others’ group. Haemoglobin, plasma ferritin, soluble transferrin receptor (sTfR), C-Reactive protein, and alpha-1-acid-glycoprotein were obtained from a non-fasting venous blood sample. Inflammation was adjusted for using the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anaemia (BRINDA) method(3). Body iron concentration (mg/kg body weight) was calculated using the ratio of sTfR and ferritin. A total of 96.3% of Pacific infants were iron sufficient, defined as body iron ≥0 mg/kg body weight and haemoglobin (Hb) ≥105 g/L, compared to 82.3% of Māori and 76.0% of ‘other’ (i.e. neither Māori nor Pacific) infants. ‘Other’ infants had the highest prevalence of iron deficiency overall, with 2.8% categorised with iron-deficiency anaemia (IDA) (body iron <0 mg/kg, haemoglobin <105 g/L), 11.8% with early ‘functional’ iron deficiency (body iron <0 mg/kg, haemoglobin ≥105 g/L), and 9.4% with iron depletion (ferritin <15 µg/L, in the absence of early ‘functional’ iron deficiency and iron deficiency anaemia). For Māori infants, 3.2% and 6.5% had IDA and early ‘functional’ iron deficiency respectively, and 8.1% were iron depleted. One (3.7%) Pacific infant was iron depleted, and the remainder were iron sufficient. Plasma ferritin and body iron concentration were, on average, higher in Pacific compared to non-Pacific infants. These findings give an up-to-date and robust understanding of the iron status of infants by ethnicity, highlighting an unexpected finding that infants who are neither Māori nor Pacific may be at higher risk of poor iron status in NZ.
The significance of human milk in an infant’s diet is well-established, yet accurately measuring human milk intake remains challenging. Current methods are either unsuitable for large-scale studies, such as the dose-to-mother stable isotope technique, or rely on set amounts of human milk, regardless of known variability in individual intake(1). There is a paucity of data on how much infants consume, particularly in later infancy (>6 months) when complementary foods have been introduced. This research aimed to estimate human milk intakes and total infant milk intakes (including infant formula) in New Zealand infants aged 7-10 months, explore factors that predict these intakes, and develop and validate equations to predict human milk intake using simple measures. Human milk intake data were obtained using the dose-to-mother stable isotope technique in infants aged 7-10 months and their mothers as part of the First Foods New Zealand study (FFNZ)(2). Predictive equations were developed using questionnaire and anthropometric data (Model 1) and additional dietary data from diet recalls (Model 2)(3). The validity of existing methods to estimate human milk intake (NHANES and ALSPAC studies) was compared against the dose-to-mother results. FFNZ included 625 infants, with 157 mother-infant dyads providing complete data for determining human milk volume. Using the dose-to-mother data, the measured mean (SD) human milk intake was 785 (264) g/day. Older infants had lower human milk and total milk intakes, male infants consumed more total milk. The strongest predictors of human milk intake were infant age, infant body mass index, number of breastfeeds a day, infant formula consumption, and energy from complementary food intake. When the predictive equations were tested, mean (95% CI) differences in predicted versus measured human milk intake (mean, [SD]: 762 [257] mL/day) were 0.0 mL/day (-26, 26) for Model 1 and 0.5 mL/day (-21, 22) for Model 2. In contrast, the NHANES and ALSPAC methods underestimated intake by 197 mL/day (-233, -161) and 175 mL/day (-216, -134), respectively. The predictive equations are presented as the Human Milk Intake Level Calculations (HuMILC) tool, designed for use in large-scale studies to more accurately estimate human milk intakes of infants. The use of objective quantifiable assessment methods enhances our understanding of infant human milk intakes, improving our ability to accurately assess nutritional adequacy in infants.
Volcanic fissure eruptions typically start with the opening of a linear fissure that erupts along its entire length, following which, activity localises to one or more isolated vents within a few hours or days. Localisation is important because it influences the spatiotemporal evolution of the hazard posed by the eruption. Previous work has proposed that localisation can arise through a thermoviscous fingering instability driven by the strongly temperature dependent viscosity of the rising magma. Here, we explore how thermoviscous localisation is influenced by the irregular geometry of natural volcanic fissures. We model the pressure-driven flow of a viscous fluid with temperature-dependent viscosity through a narrow fissure with either sinusoidal or randomised deviations from a uniform width. We identify steady states, determine their stability and quantify the degree of flow enhancement associated with localised flow. We find that, even for relatively modest variations of the fissure width (${\lt } 10$ %), the non-planar geometry supports strongly localised steady states, in which the wider parts of the fissure host faster, hotter flow, and the narrower parts of the fissure host slower, cooler flow. This geometrically driven localisation differs from the spontaneous thermoviscous fingering observed in planar geometries and can strongly impact the localisation process. We delineate the regions of parameter space under which geometrically driven localisation is significant, showing that it is a viable mechanism for the observed localisation under conditions typical of basaltic eruptions, and that it has the potential to dominate the effects of spontaneous thermoviscous fingering in these cases.
Background: Self-injurious behaviours (SIB) are repetitive, non-accidental movements that result in physical damage inflicted upon oneself, without suicidal intent. SIB are prevalent among children with autism spectrum disorder and can lead to permanent disability or death. Neuromodulation at a locus of neural circuitry implicated in SIB, the nucleus accumbens (NAc), may directly influence these behaviours. Methods: We completed a phase I, open-label clinical trial of deep brain stimulation (DBS) of the NAc in children with severe, treatment-refractory SIB (ClinicalTrials.gov NCT03982888). Participants were monitored for 12 months following NAc-DBS to assess the primary outcomes of safety and feasibility. Secondary outcomes included serial assessments of SIB, ambulatory actigraphy, and changes in brain glucose metabolism induced by DBS. Results: Six children underwent NAc-DBS without any serious adverse events. NAc-DBS resulted in significant reductions in SIB and SIB-associated behaviours across multiple standardized scales, concurrent with clinically meaningful improvements in quality-of-life. Ambulatory actigraphy showed reductions in high-amplitude limb movements and positron emission tomography revealed treatment-induced reductions in metabolic activity within the thalamus, striatum, and temporoinsular cortex. Conclusions: This first-in-children phase 1 clinical trial demonstrates the safety and feasibility of NAc-DBS in children with severe, refractory SIB at high risk of physical injury and death and supports further investigations.
Pulmonary artery capacitance is a relatively novel measurement associated with adverse outcomes in pulmonary arterial hypertension. We sought to determine if preoperative indexed pulmonary artery capacitance was related to outcomes in paediatric heart transplant recipients, describe the changes in indexed pulmonary artery capacitance after transplantation, and compare its discriminatory ability to predict outcomes as compared to conventional predictors.
Methods:
This was a retrospective study of paediatric patients who underwent heart transplant at our centre from July 2014 to May 2022. Variables from preoperative and postoperative clinical, catheterisation, and echo evaluations were recorded. The primary composite outcome measure included postoperative mortality, postoperative length of stay in the top quartile, and/or evidence of end organ dysfunction.
Results:
Of the 23 patients included in the analysis, 11 met the composite outcome. There was no statistical difference between indexed pulmonary artery capacitance values in patients who met the composite outcome [1.8 ml/mmHg/m2 (interquartile 0.8, 2.4)] and those who did not [1.4 (interquartile 0.9, 1.7)], p = 0.17. There were no significant signs of post-operative right heart failure in either group. There was no significant difference between pre-transplant and post-transplant indexed pulmonary artery capacitance or indexed pulmonary vascular resistance.
Conclusions:
Preoperative pulmonary artery capacitance was not associated with our composite outcome in paediatric heart transplant recipients. It did not appear to be additive to pulmonary vascular resistance in paediatric heart transplant patients. Pulmonary vascular disease did not appear to drive outcomes in this group.
Background: Amyotrophic Lateral Sclerosis (ALS) leads to progressive functional decline and reduced survival. Identifying clinical predictors like ALSFRS-R and FVC is essential for prognosis and disease management. Understanding progression profiles based on diagnostic characteristics supports clinical trial design and assessment of treatment response. This study evaluates disease progression and survival predictors in ALS patients from the CNDR. Methods: 1565 ALS patients in the CNDR were analyzed to assess baseline ALSFRS-R, FVC, time from symptom onset to diagnosis, and their association with disease progression and survival. Results: At diagnosis, ALSFRS-R was 44.7 (SD = 5.46), with 72.3% scoring ≥44. Mean FVC was 84.2% (SD = 23.3), with 78.3% of patients having FVC ≥65%. ALSFRS-R declined at 1.06 points/month (SD = 1.33), with faster progression in patients diagnosed within 24 months (1.61 points/month). Patients with ALSFRS-R ≥44 had a median survival of 41.8 months, compared to 30.9 months for those <44 (p < 0.001). Similarly, FVC ≥65% was associated with longer survival (35.4 vs. 29.5 months, p = 0.002). Conclusions: ALSFRS-R and FVC at diagnosis predict survival and inform clinical decision-making. These findings highlight the importance of early diagnosis and targeted interventions to slow disease progression and improve patient outcomes.
Current evidence underscores a need to transform how we do clinical research, shifting from academic-driven priorities to co-led community partnership focused programs, accessible and relevant career pathway programs that expand opportunities for career development, and design of trainings and practices to develop cultural competence among research teams. Failures of equitable research translation contribute to health disparities. Drivers of this failed translation include lack of diversity in both researchers and participants, lack of alignment between research institutions and the communities they serve, and lack of attention to structural sources of inequity and drivers of mistrust for science and research. The Duke University Research Equity and Diversity Initiative (READI) is a program designed to better align clinical research programs with community health priorities through community engagement. Organized around three specific aims, READI-supported programs targeting increased workforce diversity, workforce training in community engagement and cultural competence, inclusive research engagement principles, and development of trustworthy partnerships.
The Mental Health Bill, 2025, proposes to remove autism and learning disability from the scope of Section 3 of the Mental Health Act, 1983 (MHA). The present article represents a professional and carer consensus statement that raises concerns and identifies probable unintended consequences if this proposal becomes law. Our concerns relate to the lack of clear mandate for such proposals, conceptual inconsistency when considering other conditions that might give rise to a need for detention and the inconsistency in applying such changes to Part II of the MHA but not Part III. If the proposed changes become law, we anticipate that detentions would instead occur under the less safeguarded Deprivation of Liberty Safeguards framework, and that unmanaged risks will eventuate in behavioural consequences that will lead to more autistic people or those with a learning disability being sent to prison. Additionally, there is a concern that the proposed definitional breadth of autism and learning disability gives rise to a risk that people with other conditions may unintentionally be unable to be detained. We strongly urge the UK Parliament to amend this portion of the Bill prior to it becoming law.
Set and costume designs are a large part of worldbuilding for the plays that actors inhabit. These elements enhance and contextualize the historical, geographic, and temporal environments for the performance. August Wilson was incredibly detailed in what he asked for in his plays, not just from the actors but also from the designers. Constanza Romero and David Gallo are but two of the designers who have brought the world of Wilson’s American Century Cycle to full realization. This chapter features a conversation between Romero, Gallo, and Willa J. Taylor about their design processes and practices when working on Wilson’s plays.
The Australian SKA Pathfinder (ASKAP) offers powerful new capabilities for studying the polarised and magnetised Universe at radio wavelengths. In this paper, we introduce the Polarisation Sky Survey of the Universe’s Magnetism (POSSUM), a groundbreaking survey with three primary objectives: (1) to create a comprehensive Faraday rotation measure (RM) grid of up to one million compact extragalactic sources across the southern $\sim50$% of the sky (20,630 deg$^2$); (2) to map the intrinsic polarisation and RM properties of a wide range of discrete extragalactic and Galactic objects over the same area; and (3) to contribute interferometric data with excellent surface brightness sensitivity, which can be combined with single-dish data to study the diffuse Galactic interstellar medium. Observations for the full POSSUM survey commenced in May 2023 and are expected to conclude by mid-2028. POSSUM will achieve an RM grid density of around 30–50 RMs per square degree with a median measurement uncertainty of $\sim$1 rad m$^{-2}$. The survey operates primarily over a frequency range of 800–1088 MHz, with an angular resolution of 20” and a typical RMS sensitivity in Stokes Q or U of 18 $\mu$Jy beam$^{-1}$. Additionally, the survey will be supplemented by similar observations covering 1296–1440 MHz over 38% of the sky. POSSUM will enable the discovery and detailed investigation of magnetised phenomena in a wide range of cosmic environments, including the intergalactic medium and cosmic web, galaxy clusters and groups, active galactic nuclei and radio galaxies, the Magellanic System and other nearby galaxies, galaxy halos and the circumgalactic medium, and the magnetic structure of the Milky Way across a very wide range of scales, as well as the interplay between these components. This paper reviews the current science case developed by the POSSUM Collaboration and provides an overview of POSSUM’s observations, data processing, outputs, and its complementarity with other radio and multi-wavelength surveys, including future work with the SKA.
While dying at home is often described as desirable, to our knowledge, no reviews have focused specifically on people’s reasons for wanting to die at home. This review describes the breadth of what is known about motivations, attitudes, ideas, and reasons underlying the decision to choose “home” as one’s preferred placed of death.
Methods
This review was guided by a scoping review methodology following a five-stage approach including: (1) identify the research question, (2) identify relevant studies, (3) select studies based on inclusion/exclusion criteria, (4) chart the data, and (5) summarize and report the results.
Results
Seventeen articles were identified that met inclusion/exclusion criteria and discussed motivations underlying people’s desires to die at home. Thirty-five percent of studies were from Canada (n = 6/17), 29% were from Europe (n = 5/17), and 29% were from Asia (n = 5/17). Most studies (n = 11/17) used methods that involved collecting and/or analyzing interview data from participants, while the remaining studies (n = 6/17) used methods that involved administering and analyzing surveys or questionnaires. Characteristics of participants varied, but most commonly, studies included people with advanced illnesses who were nearing death (35% of studies, n = 6/17). Motivations for choosing a home death included desires to preserve a sense of self, factors relating to interpersonal relationships, and topics such as culture, religion, socioeconomic status, living situation, and lived experience.
Significance of results
The many interconnected reasons that lead people to choose a home death vary, as individuals have a range of motivations for choosing to die at home, which are highly influenced by contextual and cultural factors. Ultimately, this review will provide a comprehensive description of factors which may inform end-of-life planning, highlighting needs to be considered when planning the preferred location of a death.
The interaction between porous structures and flows with mean and oscillatory components has many applications in fluid dynamics. One such application is the hydrodynamic forces on offshore jacket structures from waves and current, which have been shown to give a significant blockage effect, leading to a reduction in drag forces. To better understand this, we derived analytical expressions that describe the effect of current on drag forces from large waves, and conducted experiments that measured forces on a model jacket in collinear waves and currents. We utilised symmetry and phase-inversion techniques, relying on the underlying physics of wave structure interaction, to separate Morison drag and inertia-type forces and to decompose these forces into their respective frequency harmonics. We find that the odd harmonics of the drag force mostly contain the loads from waves, while even harmonics vary much more rapidly with the current speed flowing through the jacket. At the time of peak force, these current speeds were estimated to be 40 % of the undisturbed current and 50 % of the industry-standard estimates, a result that has significant implications for design and re-assessment of jackets. At times away from the peak force, when there are no waves and only current, the blockage effects are reduced. Hence, the variation in blocked current speeds appears to occur on a relatively fast time scale similar to the compact wave envelope. These findings may be generalisable to any jacket-type structure in flows with mean and high Keulegan–Carpenter number oscillatory components.
Objectives/Goals: Research supports the use of music to improve the care and well-being of adults living with dementia; however, the practice and implementation of music in elder care communities is not regulated. The goal of this qualitative study was to survey elder care communities in Northeast Kansas to determine the use of music with people living with dementia. Methods/Study Population: We interviewed staff (n = 10) at five elder care communities in the Kansas City Metro area and observed musical activities and artifacts in shared living spaces within each community. Interview questions included details of the frequency and purpose of using music, who determined which music to use, and any effects, positive or negative, the interviewee believed to be associated with the use of music. Musical events, visiting musicians or music therapists leading group sing-alongs were observed at two communities, and music-related activities led by staff were observed at two others. Results/Anticipated Results: Music was used in some way at each of the five communities. Each location had recorded music available to residents in the shared living spaces, and most had a piano in the main lounge area. During the sing-along and music-related activities, residents were observed singing along to songs from memory, engaging with one another and the group leader and smiling. Staff employed by each community varied in their level of musical training and experience, from none to a full-time music therapist in residence. Staff interviewed said they believed music was helpful to aid memory recall, reduce anxiety, and to engage interest. Interestingly, a music therapist at one site also described how music during mealtimes created too much of a distraction for residents and interfered with dietary care. Discussion/Significance of Impact: It is clear from both the staff interviews and direct observations of musical activities that music is important to consider for people living with dementia in care communities. Guidelines for implementation and minimum standards would be helpful to ensure all care community residents can experience benefits highlighted by staff in this study.
Objectives/Goals: Mayo Clinic Florida’s Clinical Research Units develop over 200 clinical studies on average annually. Almost 30% of these projects are developed and then are unable to activate due to a variety of operational factors. To increase the success rate, a scoring tool was created to assess the risk associated with the development of these research projects. Methods/Study Population: A project team comprised of members of research administration and physician leadership developed a rapid project management (RPM) scoring tool to assess operational risk factors. The scoring algorithm was embedded into an existing REDCap database, using a combination of identified variables and calculated fields. All noncancer industry sponsor-initiated clinical studies were scored at intake. According to the following categories: enrollment timelines, study team capacity, and previous experience with the Sponsor. Studies with a score greater than the established threshold were referred to physician leadership for transparent discussions with the principal investigator regarding the identified study development-related risks. Results/Anticipated Results: The RPM tool has assessed close to 200 projects since implementation in June 2022. An interim analysis is being conducted of all projects assessed by the RPM tool dating from implementation to May 2024 to compare the outcomes of these studies with the given RPM score. We anticipate based on anecdotal evidence gathered during the course of this pilot project that the RPM tool will show a correlation between risks identified and study outcomes as defined as successful activation of trials, or rationale of project development failures. We anticipate a reduction in the amount of time elapsed and effort expended developing projects with scores reflecting identified project development-related risk factors. Discussion/Significance of Impact: The RPM tool provides an opportunity to allocate resources to studies with the greatest potential for successful activation. In the future, the RPM tool may be used to identify risk factors associated with enrollment and accrual of participants.
Objectives/Goals: Imaging neuromas, benign tumors of nerve tissue, can be difficult in amputees with osseointegrated (OI) prostheses, in which a metal rod is implanted into the residual limb. Magnetic resonance imaging can be inadequate due to the implanted metal. The aim of this study is to assess the use of ultrasound to detect neuromas in patients with OI prostheses. Methods/Study Population: This is a single-institutional observational study of 7 patients undergoing lower limb OI prostheses. Lower extremity nerve ultrasounds with 2-D grayscale and Doppler were completed at postoperative follow-up visits following OI prosthesis implantation. Specifically, the sciatic nerve, tibial nerve, common peroneal nerve, and sural nerve were targeted for imaging. Neuromas found on ultrasound were measured by maximal length in three planes. Results/Anticipated Results: Our study to date includes two patients with OI prostheses. The remaining patients will be accrued by the end of December. The first patient with a left below-the-knee amputation completed imaging 3 years after OI prosthesis implantation. The common peroneal nerve showed preserved fascicular architecture and morphology, with no distinct neuroma formation. However, the sural nerve demonstrated a 6 × 5 × 4 mm neuroma with minimal pain with deep palpation. The tibial nerve demonstrated a 14 × 11 × 8 mm neuroma within the medial calf musculature, with mild pain with deep palpation. The second patient with a right above-the-knee amputation was imaged 10 months after OI prosthesis implantation. The sciatic nerve demonstrated preserved fascicular morphology and terminated in a smooth taper. There was no defined neuroma. Discussion/Significance of Impact: In conclusion, we have preliminarily shown in the first two patients that ultrasound can successfully image neuromas in patients with OI prostheses in the postoperative period. Furthermore, despite a patient that was 3 years postoperative with two neuromas, the neuromas produced minimal to mild pain with targeted palpation.
We conducted a pilot study of implementing community health workers (CHWs) to assist patients with hypertension and social needs. As part of clinical care, patients identified as having an unmet need were referred to a CHW. We evaluated changes in blood pressure and needs among 35 patients and conducted interviews to understand participants’ experiences. Participants had a mean age of 54.1 years and 29 were Black. Twenty-six completed follow-up. Blood pressure and social needs improved from baseline to 6 months. Participants reported being accepting of CHWs, but also challenges with establishing a relationship with a CHW and being unclear about their role.
Many post-acute and long-term care settings (PALTCs) struggle to measure antibiotic use via the standard metric, days of therapy (DOT) per 1000 days of care (DOC). Our objective was to develop antibiotic use metrics more tailored to PALTCs.
Design:
Retrospective cohort study with a validation cohort.
Setting:
PALTC settings within the same network.
Methods:
We obtained census data and pharmacy dispensing data for 13 community PALTCs (January 2020–December 2023). We calculated antibiotic DOT/1000 DOC, DOT per unique residents, and antibiotic starts per unique residents, at monthly intervals for community PALTCs. The validation cohort was 135 Veterans Affairs Community Living Centers (VA CLCs). For community PALTCs only, we determined the DOT and antibiotics starts per unique residents cared for by individual prescribers.
Results:
For community PALTCs, the correlation between facility-level antibiotic DOT/1000 DOC and antibiotic DOT/unique residents and antibiotic courses/unique residents was 0.97 (P < 0.0001) and 0.84 (P < 0.0001), respectively. For VA CLCs, those values were 0.96 (P < 0.0001) and 0.85 (P < 0.0001), respectively. At community PALTCs, both novel metrics permitted assessment and comparison of antibiotic prescribing among practitioners.
Conclusion:
At the facility level, the novel metric antibiotic DOT/unique residents demonstrated strong correlation with the standard metric. In addition to supporting tracking and reporting of antibiotic use among PALTCs, antibiotic DOT/unique residents permits visualization of the antibiotic prescribing rates among individual practitioners, and thus peer comparison, which in turn can lead to actionable feedback that helps improve antibiotic use in the care of PALTC residents.
Hallucinations are common and distressing symptoms in Parkinson’s disease (PD). Treatment response in clinical trials is measured using validated questionnaires, including the Scale for Assessment of Positive Symptoms-Hallucinations (SAPS-H) and University of Miami PD Hallucinations Questionnaire (UM-PDHQ). The minimum clinically important difference (MCID) has not been determined for either scale. This study aimed to estimate a range of MCIDs for SAPS-H and UM-PDHQ using both consensus-based and statistical approaches.
Methods
A Delphi survey was used to seek opinions of researchers, clinicians, and people with lived experience. We defined consensus as agreement ≥75%. Statistical approaches used blinded data from the first 100 PD participants in the Trial for Ondansetron as Parkinson’s Hallucinations Treatment (TOP HAT, NCT04167813). The distribution-based approach defined the MCID as 0.5 of the standard deviation of change in scores from baseline at 12 weeks. The anchor-based approach defined the MCID as the average change in scores corresponding to a 1-point improvement in clinical global impression-severity scale (CGI-S).
Results
Fifty-one researchers and clinicians contributed to three rounds of the Delphi survey and reached consensus that the MCID was 2 points on both scales. Sixteen experts with lived experience reached the same consensus. Distribution-defined MCIDs were 2.6 points for SAPS-H and 1.3 points for UM-PDHQ, whereas anchor-based MCIDs were 2.1 and 1.3 points, respectively.
Conclusions
We used triangulation from multiple methodologies to derive the range of MCID estimates for the two rating scales, which was between 2 and 2.7 points for SAPS-H and 1.3 and 2 points for UM-PDHQ.