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Millions of adults and children are exposed to high levels of lead, a neurotoxicant, each year. Recent evidence suggests that lead exposure may precipitate neurodegeneration, particularly if the exposure occurs early or late in life, with unique alterations to the structure or function of specific subfields of the hippocampus, a region involved in memory and Alzheimer's disease. It has been proposed that specific hippocampal subfields may thus be useful biomarkers for lead-associated neurological disease. We turned to a population-representative New Zealand birth cohort where the extent of lead exposure was not confounded by social class (the Dunedin Study; born 1972–1973 and followed to age 45) to test the hypothesis that early life lead exposure (blood-lead level at age 11 years) is associated with smaller MRI-assessed gray matter volumes of specific subfields of the hippocampus at age 45 years. Among the 508 Dunedin Study members with childhood lead data and adult MRI data passing quality control (93.9 % of those with lead data who attended the age-45 assessment wave, 240[47.2 %] female), childhood blood-lead levels ranged from 4 to 31 µg/dL (M[SD]=10.9[4.6]). Total hippocampal volumes were lower among adults with higher childhood blood-lead levels (b=-102.6 mm3 per 5 ug/dL-unit greater blood-lead level, 95 %CI: −175.4 to −29.7, p =.006 , β=-.11), as were all volumes of the 24 hemisphere-specific subfields of the hippocampus. Of these 24 subfields, 20 demonstrated negative lead-associations greater than β=-.05 in size, 14 were statistically significant after adjustment for multiple comparisons (p FDR <.05), and 9 remained significant after adjustment for potential confounders and multiple comparisons. Children exposed to lead demonstrate smaller volumes across all subfields of the hippocampus in midlife. The hypothesis that lead selectively impairs specific subfields of the hippocampus, or that specific subfields may be markers for lead-associated neurological disease, requires further evaluation. • Children with higher blood-lead levels had smaller hippocampal volumes in midlife. • These deficits reflected smaller volumes of all 24 hemisphere-specific hippocampal subfields. • Lead-hippocampus toxicity may not be subfield specific. • Individual hippocampal subfields may not be uniquely sensitive markers for lead-related neurological disease. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Interprofessional collaboration leads to better patient care, enhanced teamwork skills, better communication, and enhanced understandings of each other's professional roles. METHODS: The objective of the study was to trial an interprofessional education (IPE) simulation activity with students (nine) from three health and social service disciplines in one community polytechnic. A pre-test/post-test design was used to gather data on the students' perspectives of the IPE simulation and what the students learned from it. A simple Likert Scale questionnaire and two focus groups (with five and four participants, respectively) were conducted. A thematic analysis of the focus group data was undertaken while survey responses are presented in percentages for ease of readability. FINDINGS: The participants enjoyed the simulation, had greater confidence with interprofessional communication post-participation and increased knowledge of each other's scope of practice. The participants welcomed the opportunity to practise handover, which was an area of concern for all. IMPLICATIONS: IPE is an invaluable tool for preparing students for their future careers as members of an interdisciplinary health team. [ABSTRACT FROM AUTHOR]

Background: Acute rheumatic fever (ARF) is a serious sequela of Group A Streptococcus (GAS) infection associated with significant global mortality. Pathogenesis remains poorly understood, with the current prevailing hypothesis based on molecular mimicry and the notion that antibodies generated in response to GAS infection cross-react with cardiac proteins such as myosin. Contemporary investigations of the broader autoantibody response in ARF are needed to both inform pathogenesis models and identify new biomarkers for the disease. Methods: This study has utilised a multi-platform approach to profile circulating autoantibodies in ARF. Sera from patients with ARF, matched healthy controls and patients with uncomplicated GAS pharyngitis were initially analysed for autoreactivity using high content protein arrays (Protoarray, 9000 autoantigens), and further explored using a second protein array platform (HuProt Array, 16,000 autoantigens) and 2-D gel electrophoresis of heart tissue combined with mass spectrometry. Selected autoantigens were orthogonally validated using conventional immunoassays with sera from an ARF case-control study (n=79 cases and n=89 matched healthy controls) and a related study of GAS pharyngitis (n=39) conducted in New Zealand. Results: Global analysis of the protein array data showed an increase in total autoantigen reactivity in ARF patients compared with controls, as well as marked heterogeneity in the autoantibody profiles between ARF patients. Autoantigens previously implicated in ARF pathogenesis, such as myosin and collagens were detected, as were novel candidates. Disease pathway analysis revealed several autoantigens within pathways linked to arthritic and myocardial disease. Orthogonal validation of three novel autoantigens (PTPN2, DMD and ANXA6) showed significant elevation of serum antibodies in ARF (p < 0.05), and further highlighted heterogeneity with patients reactive to different combinations of the three antigens. Conclusions: The broad yet heterogenous elevation of autoantibodies observed suggests epitope spreading, and an expansion of the autoantibody repertoire, likely plays a key role in ARF pathogenesis and disease progression. Multiple autoantigens may be needed as diagnostic biomarkers to capture this heterogeneity. [ABSTRACT FROM AUTHOR]

Introduction: The System Level Framework (SLMF) is a policy introduced by New Zealand's Ministry of Health in 2016 with the aim of improving health outcomes by stimulating inter-organisational integration at the local level. We sought to understand which conditions that vary at the local level are most important in shaping successful implementation of this novel and internationally significant policy initiative relevant to integrated care. Strategy and Methods: We conducted 50 interviews with managers and clinicians who were directly involved in SLM implementation during 2018. Interview data was supplemented with the SLM Improvement Plans of all districts over the first three years of implementation. We used Qualitative Comparative Analysis (QCA) to identify the combinations and configurations of necessary and sufficient conditions of successful implementation. Results: We found that the strength of formal and informal organisational relationships at the local level were critical conditions for implementation success, and that while fidelity to the policy programme was necessary, it was not sufficient. Broader contextual features such as population size and complexity of the organisational environment were less important. The SLMF was able to deepen and widen inter-organisational collaboration where it already existed but could not mitigate the legacies of weaker relationships. Discussion: The two dimensions of implementation success, 'Maturity of SLM Improvement Plan Processes' and 'Data Sophistication and Use' were closely related. Broadly, our findings support the contention that integrated approaches to health system improvement at the local level require collaborative, trust-based approaches with an emphasis on iterative learning, including the willingness to share data between organisations. Conclusion: In the context of integrated care, our findings support the need to focus on establishing the conditions that build collaborative governance in addition to strengthening it when it already exists. [ABSTRACT FROM AUTHOR]

Objectives: Circulating antibodies are important markers of previous infection and immunity. Questions remain with respect to the durability and functionality of SARS‐CoV‐2 antibodies. This study explored antibody responses in recovered COVID‐19 patients in a setting where the probability of re‐exposure is effectively nil, owing to New Zealand's successful elimination strategy. Methods: A triplex bead‐based assay that detects antibody isotype (IgG, IgM and IgA) and subclass (IgG1, IgG2, IgG3 and IgG4) responses against Nucleocapsid (N) protein, the receptor binding domain (RBD) and Spike (S) protein of SARS‐CoV‐2 was developed. After establishing baseline levels with pre‐pandemic control sera (n = 113), samples from PCR‐confirmed COVID‐19 patients with mild–moderate disease (n = 189) collected up to 8 months post‐infection were examined. The relationship between antigen‐specific antibodies and neutralising antibodies (NAbs) was explored with a surrogate neutralisation assay that quantifies inhibition of the RBD/hACE‐2 interaction. Results: While most individuals had broad isotype and subclass responses to each antigen shortly after infection, only RBD and S protein IgG, as well as NAbs, were relatively stable over the study period, with 99%, 96% and 90% of samples, respectively, having responses over baseline 4–8 months post‐infection. Anti‐RBD antibodies were strongly correlated with NAbs at all time points (Pearson's r ≥ 0.87), and feasibility of using finger prick sampling to accurately measure anti‐RBD IgG was demonstrated. Conclusion: Antibodies to SARS‐CoV‐2 persist for up to 8 months following mild‐to‐moderate infection. This robust response can be attributed to the initial exposure without immune boosting given the lack of community transmission in our setting. [ABSTRACT FROM AUTHOR]

INTRODUCTION: In 2016, the New Zealand Ministry of Health introduced the System Level Measures (SLM) framework as a new approach to health system improvement that emphasised quality improvement and integration. A funding stream that was a legacy of past primary care performance management was repurposed as 'capacity and capability' funding to support the implementation of the SLM framework. AIM: This study explored how the capacity and capability funding has been used and the issues and challenges that have arisen from the funding implementation. METHODS: Semi-structured interviews with 50 key informants from 18 of New Zealand's 20 health districts were conducted. Interview transcripts were coded using thematic analysis. RESULTS: The capacity and capability funding was used in three different ways. Approximately one-third of districts used it to actively support quality improvement and integration initiatives. Another one-third tweaked existing performance incentive schemes and in the remaining one-third, the funding was passed directly on to general practices without strings attached. Three key issues were identified related to implementation of the capacity and capability funding: lack of clear guidance regarding the use of the funding; funding perceived as a barrier to integration; and funding seen as insufficient for intended purposes. DISCUSSION: The capacity and capability funding was intended to support collaborative integration and quality improvement between health sector organisations at the district level. However, there is a mismatch between the purpose of the capacity and capability funding and its use in practice, which is primarily a product of incremental and inconsistent policy development regarding primary care improvement. [ABSTRACT FROM AUTHOR]

Background: Serological assays that detect antibodies to SARS-CoV-2 are critical for determining past infection and investigating immune responses in the COVID-19 pandemic. We established ELISA-based immunoassays using locally produced antigens when New Zealand went into a nationwide lockdown and the supply chain of diagnostic reagents was a widely held domestic concern. The relationship between serum antibody binding measured by ELISA and neutralising capacity was investigated using a surrogate viral neutralisation test (sVNT). Methods: A pre-pandemic sera panel (n = 113), including respiratory infections with symptom overlap with COVID-19, was used to establish assay specificity. Sera from PCR-confirmed SARS-CoV-2 patients (n = 21), and PCR-negative patients with respiratory symptoms suggestive of COVID-19 (n = 82) that presented to the two largest hospitals in Auckland during the lockdown period were included. A two-step IgG ELISA based on the receptor binding domain (RBD) and spike protein was adapted to determine seropositivity, and neutralising antibodies that block the RBD/hACE-2 interaction were quantified by sVNT. Results: The calculated cut-off (>0.2) in the two-step ELISA maximised specificity by classifying all pre-pandemic samples as negative. Sera from all PCR-confirmed COVID-19 patients were classified as seropositive by ELISA _7 days after symptom onset. There was 100% concordance between the two-step ELISA and the sVNT with all 7+ day sera from PCR-confirmed COVID-19 patients also classified as positive with respect to neutralising antibodies. Of the symptomatic PCR-negative cohort, one individual with notable travel history was classified as positive by two-step ELISA and sVNT, demonstrating the value of serology in detecting prior infection. Conclusions: These serological assays were established and assessed at a time when human activity was severely restricted in New Zealand. This was achieved by generous sharing of reagents and technical expertise by the international scientific community, and highly collaborative efforts of scientists and clinicians across the country. The assays have immediate utility in supporting clinical diagnostics, understanding transmission in high-risk cohorts and underpinning longer-term 'exit' strategies based on effective vaccines and therapeutics. [ABSTRACT FROM AUTHOR]

Background: Mixing alcohol with energy drinks (AmED use) has been purported to increase risky behavior and alcohol consumption. The current study applied a within-subject retrospective self-report design to examine the association between AmED use (versus alcohol-only) and risky behavior, alcohol consumption and motivations. Method: New Zealand alcohol consumers aged 18–35 years (n = 289; AmED users: n = 143) completed an online survey. Results: Compared to alcohol-only, AmED use was associated with significant reductions in nine of twenty-six risk taking behaviors. The average amount of alcohol consumed did not differ between sessions. Maximum alcohol intake was greater in alcohol-only sessions than in AmED sessions. Motivations for consuming AmEDs and beliefs on their effects were not related to differences in typical alcohol intake in either session. The motivation to drink AmED "for the thrill" was associated with a higher general risk-taking propensity score, but not motivations and beliefs relating to being in control and feeling less drunk. AmED users did not have a significantly higher general risk-taking propensity than non-users. Conclusions: AmED use does not appear to increase risk-taking behavior or alcohol consumption and is associated with decreased risk-taking behavior and binge drinking. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Reforms have been introduced since 2000 to make New Zealand's health system primary care-led. A competent health management workforce is necessary to provide leadership for the goals of the reforms to be realised. AIM AND OBJECTIVE: To review New Zealand's key primary health care policies from 2000 to 2016 and consider their implications for management and leadership. METHODS: A document analysis was undertaken using qualitative content analysis. Eligible documents were identified through the websites of relevant government and nongovernment agencies, World Health Organisation, and through Google Scholar. FINDINGS: Two key policy trends relating to primary health care were identified. Firstly, a population health orientation to improve access to health care through community participation, and secondly, an integrated approach to promote collaboration within the health system, and between the health system and other sectors. The inferred management and leadership skillsets required to realise these policies included relationship management and collaboration, change management, and leadership. CONCLUSION: New Zealand's primary health care sector underwent substantial reform between 2000 and 2016. Management and leadership capabilities need to be strengthened and developed for the benefits of the reforms to be realised. [ABSTRACT FROM AUTHOR]

Importance: Millions of adults now entering middle age were exposed to high levels of lead, a developmental neurotoxin, as children. Although childhood lead exposure has been linked to disrupted behavioral development, the long-term consequences for adult mental and behavioral health have not been fully characterized.Objective: To examine whether childhood lead exposure is associated with greater psychopathology across the life course and difficult adult personality traits.Design, Setting, and Participants: This prospective cohort study was based on a population-representative birth cohort of individuals born between April 1, 1972, and March 31, 1973, in Dunedin, New Zealand, the Dunedin Multidisciplinary Health and Development Study. Members were followed up in December 2012 when they were 38 years of age. Data analysis was performed from March 14, 2018, to October 24, 2018.Exposures: Childhood lead exposure ascertained as blood lead levels measured at 11 years of age. Blood lead levels were unrelated to family socioeconomic status.Main Outcomes and Measures: Primary outcomes were adult mental health disorder symptoms assessed through clinical interview at 18, 21, 26, 32, and 38 years of age and transformed through confirmatory factor analysis into continuous measures of general psychopathology and internalizing, externalizing, and thought disorder symptoms (all standardized to a mean [SD] of 100 [15]) and adult personality assessed through informant report using the Big Five Personality Inventory (assessing neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness) at 26, 32, and 38 years of age (all scores standardized to a mean [SD] of 0 [1]). Hypotheses were formulated after data collection; an analysis plan was posted in advance.Results: Of 1037 original study members, 579 (55.8%) were tested for lead exposure at 11 years of age (311 [53.7%] male). The mean (SD) blood lead level was 11.08 (4.96) μg/dL. After adjusting for study covariates, each 5-μg/dL increase in childhood blood lead level was associated with a 1.34-point increase (95% CI, 0.11-2.57; P = .03) in general psychopathology, driven by internalizing (b = 1.41; 95% CI, 0.19-2.62; P = .02) and thought disorder (b = 1.30; 95% CI, 0.06-2.54; P = .04) symptoms. Each 5-μg/dL increase in childhood blood lead level was also associated with a 0.10-SD increase in neuroticism (95% CI, 0.02-0.08; P = .02), a 0.09-SD decrease in agreeableness (95% CI, -0.18 to -0.01; P = .03), and a 0.14-SD decrease in conscientiousness (95% CI, -0.25 to -0.03; P = .01). There were no statistically significant associations with informant-rated extraversion (b = -0.09; 95% CI, -0.17 to 0.004; P = .06) and openness to experience (b = -0.07; 95% CI, -0.17 to 0.03; P = .15).Conclusions and Relevance: In this multidecade, longitudinal study of lead-exposed children, higher childhood blood lead level was associated with greater psychopathology across the life course and difficult adult personality traits. Childhood lead exposure may have long-term consequences for adult mental health and personality. [ABSTRACT FROM AUTHOR]

Importance: Many children in the United States and around the world are exposed to lead, a developmental neurotoxin. The long-term cognitive and socioeconomic consequences of lead exposure are uncertain.Objective: To test the hypothesis that childhood lead exposure is associated with cognitive function and socioeconomic status in adulthood and with changes in IQ and socioeconomic mobility between childhood and midlife.Design, Setting, and Participants: A prospective cohort study based on a population-representative 1972-1973 birth cohort from New Zealand; the Dunedin Multidisciplinary Health and Development Study observed participants to age 38 years (until December 2012).Exposures: Childhood lead exposure ascertained as blood lead levels measured at age 11 years. High blood lead levels were observed among children from all socioeconomic status levels in this cohort.Main Outcomes and Measures: The IQ (primary outcome) and indexes of Verbal Comprehension, Perceptual Reasoning, Working Memory, and Processing Speed (secondary outcomes) were assessed at age 38 years using the Wechsler Adult Intelligence Scale-IV (WAIS-IV; IQ range, 40-160). Socioeconomic status (primary outcome) was assessed at age 38 years using the New Zealand Socioeconomic Index-2006 (NZSEI-06; range, 10 [lowest]-90 [highest]).Results: Of 1037 original participants, 1007 were alive at age 38 years, of whom 565 (56%) had been lead tested at age 11 years (54% male; 93% white). Mean (SD) blood lead level at age 11 years was 10.99 (4.63) µg/dL. Among blood-tested participants included at age 38 years, mean WAIS-IV score was 101.16 (14.82) and mean NZSEI-06 score was 49.75 (17.12). After adjusting for maternal IQ, childhood IQ, and childhood socioeconomic status, each 5-µg/dL higher level of blood lead in childhood was associated with a 1.61-point lower score (95% CI, -2.48 to -0.74) in adult IQ, a 2.07-point lower score (95% CI, -3.14 to -1.01) in perceptual reasoning, and a 1.26-point lower score (95% CI, -2.38 to -0.14) in working memory. Associations of childhood blood lead level with deficits in verbal comprehension and processing speed were not statistically significant. After adjusting for confounders, each 5-µg/dL higher level of blood lead in childhood was associated with a 1.79-unit lower score (95% CI, -3.17 to -0.40) in socioeconomic status. An association between greater blood lead levels and a decline in IQ and socioeconomic status from childhood to adulthood was observed with 40% of the association with downward mobility mediated by cognitive decline from childhood.Conclusions and Relevance: In this cohort born in New Zealand in 1972-1973, childhood lead exposure was associated with lower cognitive function and socioeconomic status at age 38 years and with declines in IQ and with downward social mobility. Childhood lead exposure may have long-term ramifications. [ABSTRACT FROM AUTHOR]

Background:Physiotherapy plays an important role in management of acute nonspecific low back pain (NSLBP). However, there is a relative dearth of information about the current clinical practice for management of NSLBP and its relationships with clinical outcomes of pain and function. Objective:To investigate the current physiotherapy practice patterns in management of acute NSLBP in New Zealand (NZ), and determine its relationships with clinical outcomes of pain and function. Methods:A prospective observational cohort study, using data from private physiotherapy clinics, was conducted. Physiotherapists at each clinic completed a treatment summary form at time of discharge. Treatment techniques used and clinical outcome of pain [numeric pain rating scale (NPRS)] and function [Patient-specific Function scale (PSFS)] were extracted from recorded notes. Raw values of NPRS and PSFS were converted to percentage of available change scores and used for further analysis. Results and Conclusions:A total of 199 data-sets of acute NSLBP patients were included in the analysis. A wide variety of treatment techniques were used by NZ physiotherapists, with joint mobilization being the most popular form of treatment choice (88%), often combined with specific exercises and massage (21%). Linear regression analysis demonstrated a significant positive association between joint mobilization and massage and patient’s function, and pain and function, respectively; whereas, a significant negative association between specific exercises and patient’s function. The most popular form of treatments used by NZ physiotherapists’ lacks support from evidence-based clinical guidelines, but still seems to be effective in reducing pain and improving function. [ABSTRACT FROM AUTHOR]

Thje article reports on the emerging technological arms competition underway between the United States and Russia and China and the possible New Zealand response. The defense technologies and the missile defense mechanisms being developed at United States and Russia and China are discussed and views of New Zealand on the developments are discussed.

We tested the accuracy of an invasive aquatic plant risk assessment system in the United States that we modified from a system originally developed by New Zealand's Biosecurity Program. The US system is comprised of 38 questions that address biological, historical, and environmental tolerance traits. Values associated with each response are summed to produce a total score for each species that indicates its risk of invasion. To calibrate and test this risk assessment, we identified 39 aquatic plant species that are major invaders in the continental US, 31 species that have naturalized but have no documented impacts (minor invaders), and 60 that have been introduced but have not established. These species represent 55 families and span all aquatic plant growth forms. We found sufficient information to assess all but three of these species. When the results are compared to the known invasiveness of the species, major invaders are distinguished from minor and non-invaders with 91% accuracy. Using this approach, the US aquatic weed risk assessment correctly identifies major invaders 85%, and non-invaders 98%, of the time. Model validation using an additional 10 non-invaders and 10 invaders resulted in 100% accuracy for the former, and 80% accuracy for the latter group. Accuracy was further improved to an average of 91% for all groups when the 17% of species with scores of 31-39 required further evaluation prior to risk classification. The high accuracy with which we can distinguish non-invaders from harmful invaders suggests that this tool provides a feasible, pro-active system for pre-import screening of aquatic plants in the US, and may have additional utility for prioritizing management efforts of established species. [ABSTRACT FROM AUTHOR]

Aquatic invasive species cause deleterious environmental and economic impacts, and are rapidly spreading through ecosystems worldwide. Despite this, very few data sets exist that describe both the presence and the absence of invaders over long time periods. We have used Geographical Information Systems (GIS) to analyse time-series data describing the spread of the freshwater invasive New Zealand mudsnail, Potamopyrgus antipodarum, in Victoria, Australia, over 110 years. We have mapped the snail's spread, estimated the percentage of stream length invaded through time, calculated the functional form of the spread rate, and investigated the role that the two proposed vectors — fish stocking and angling — have had in this invasion. Since it was first found in 1895, P. antipodarum has expanded its range in Victoria and now occurs throughout much of the southern and central areas of the state. The north of the state is relatively less invaded than the south, with the division corresponding approximately to the presence of the Great Dividing Range. We show that the snail's range has been increasing at an approximately exponential rate and estimate that 20% of total Victorian stream length is currently invaded. We also show that using long-term data can change the outcome of analyses of the relationship between vectors of spread and invasion status of separate catchments. When our time-series data were aggregated through time, the total numbers of fish stocking events and angling activity were both correlated with invasion. However, when the time-series data were used and the number of fish stocking events calculated up until the date of invasion, no relationships with stocking were found. These results underline the role that time-series data, based on both presences and absences, have to play when investigating the spread of invasive species. [ABSTRACT FROM AUTHOR]

The ability of a third dose of the Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine to stimulate immune responses against subvariants, including Omicron BA.1, has not been assessed in New Zealand populations. Unlike many overseas populations, New Zealanders were largely infection naïve at the time they were boosted. This adult cohort of 298 participants, oversampled for at-risk populations, was composed of 29% Māori and 28% Pacific peoples, with 40% of the population aged 55+. A significant proportion of the cohort was obese and presented with at least one comorbidity. Sera were collected 28 days and 6 months post second vaccination and 28 days post third vaccination. SARS-CoV-2 anti-S IgG titres and neutralising capacity using surrogate viral neutralisation assays against variants of concern, including Omicron BA.1, were investigated. The incidence of SARS-CoV-2 infection, within our cohort, prior to third vaccination was very low (<6%). This study found a third vaccine significantly increased the mean SARS-CoV-2 anti-S IgG titres, for every demographic subgroup, by a minimum of 1.5-fold compared to titres after two doses. Diabetic participants experienced a greater increase (∼4-fold) in antibody titres after their third vaccination, compared to non-diabetics (increase of ∼ 2-fold). This corrected for the deficiency in antibody titres within diabetic participants which was observed following two doses. A third dose also induced a neutralising response against Omicron variant BA.1, which was absent after two doses. This neutralising response improved regardless of age, BMI, ethnicity, or diabetes status. Participants aged ≥75 years consistently had the lowest SARS-CoV-2 anti-S IgG titres at each timepoint, however experienced the greatest improvement after three doses compared to younger participants. This study shows that in the absence of prior SARS-CoV-2 infection, a third Pfizer-BioNTech BNT162b2 vaccine enhances immunogenicity, including against Omicron BA.1, in a cohort representative of at-risk groups in the adult New Zealand population. [ABSTRACT FROM AUTHOR]

There is very little known about SARS-CoV-2 vaccine immune responses in New Zealand populations at greatest risk for serious COVID-19 disease. This prospective cohort study assessed immunogenicity in BNT162b2 mRNA vaccine recipients in New Zealand without previous COVID-19, with enrichment for Māori, Pacific peoples, older adults ≥ 65 years of age, and those with co-morbidities. Serum samples were analysed at baseline and 28 days after second dose for presence of quantitative anti-S IgG by chemiluminescent microparticle immunoassay and for neutralizing capacity against Wuhan, Beta, Delta, and Omicron BA.1 strains using a surrogate viral neutralisation assay. 285 adults with median age of 52 years were included. 55% were female, 30% were Māori, 28% were Pacific peoples, and 26% were ≥ 65 years of age. Obesity, cardiac and pulmonary disease and diabetes were more common than in the general population. All participants received 2 doses of BNT162b2 vaccine. At 28 days after second vaccination, 99.6% seroconverted to the vaccine, and anti-S IgG and neutralising antibody levels were high across gender and ethnic groups. IgG and neutralising responses declined with age. Lower responses were associated with age ≥ 75 and diabetes, but not BMI. The ability to neutralise the Omicron BA.1 variant in vitro was severely diminished but maintained against other variants of concern. Vaccine antibody responses to BNT162b2 were generally robust and consistent with international data in this COVID-19 naïve cohort with representation of key populations at risk for COVID-19 morbidity. Subsequent data on response to boosters, durability of responses and cellular immune responses should be assessed with attention to elderly adults and diabetics. [ABSTRACT FROM AUTHOR]

Background: The monoclonal antibody m102.4 is a potent, fully human antibody that neutralises Hendra and Nipah viruses in vitro and in vivo. We aimed to investigate the safety, tolerability, pharmacokinetics, and immunogenicity of m102.4 in healthy adults.Methods: In this double-blind, placebo-controlled, single-centre, dose-escalation, phase 1 trial of m102.4, we randomly assigned healthy adults aged 18-50 years with a body-mass index of 18·0-35·0 kg/m2 to one of five cohorts. A sentinel pair for each cohort was randomly assigned to either m102.4 or placebo. The remaining participants in each cohort were randomly assigned (5:1) to receive m102.4 or placebo. Cohorts 1-4 received a single intravenous infusion of m102.4 at doses of 1 mg/kg (cohort 1), 3 mg/kg (cohort 2), 10 mg/kg (cohort 3), and 20 mg/kg (cohort 4), and were monitored for 113 days. Cohort 5 received two infusions of 20 mg/kg 72 h apart and were monitored for 123 days. The primary outcomes were safety and tolerability. Secondary outcomes were pharmacokinetics and immunogenicity. Analyses were completed according to protocol. The study was registered on the Australian New Zealand Clinical Trials Registry, ACTRN12615000395538.Findings: Between March 27, 2015, and June 16, 2016, 40 (52%) of 77 healthy screened adults were enrolled in the study. Eight participants were assigned to each cohort (six received m102.4 and two received placebo). 86 treatment-emergent adverse events were reported, with similar rates between placebo and treatment groups. The most common treatment-related event was headache (12 [40%] of 30 participants in the combined m102.4 group, and three [30%] of ten participants in the pooled placebo group). No deaths or severe adverse events leading to study discontinuation occurred. Pharmacokinetics based on those receiving m102.4 (n=30) were linear, with a median half-life of 663·3 h (range 474·3-735·1) for cohort 1, 466·3 h (382·8-522·3) for cohort 2, 397·0 h (333·9-491·8) for cohort 3, and 466·7 h (351·0-889·6) for cohort 4. The elimination kinetics of those receiving repeated dosing (cohort 5) were similar to those of single-dose recipients (median elimination half-time 472·0 [385·6-592·0]). Anti-m102.4 antibodies were not detected at any time-point during the study.Interpretation: Single and repeated dosing of m102.4 were well tolerated and safe, displayed linear pharmacokinetics, and showed no evidence of an immunogenic response. This study will inform future dosing regimens for m102.4 to achieve prolonged exposure for systemic efficacy to prevent and treat henipavirus infections.Funding: Queensland Department of Health, the National Health and Medical Research Council, and the National Hendra Virus Research Program. [ABSTRACT FROM AUTHOR]

Introduction: Dementia risk may be elevated in socioeconomically disadvantaged neighborhoods. Reasons for this remain unclear, and this elevation has yet to be shown at a national population level., Methods: We tested whether dementia was more prevalent in disadvantaged neighborhoods across the New Zealand population (N = 1.41 million analytic sample) over a 20-year observation. We then tested whether premorbid dementia risk factors and MRI-measured brain-structure antecedents were more prevalent among midlife residents of disadvantaged neighborhoods in a population-representative NZ-birth-cohort (N = 938 analytic sample)., Results: People residing in disadvantaged neighborhoods were at greater risk of dementia (HR per-quintile-disadvantage-increase = 1.09, 95% confidence interval [CI]:1.08-1.10) and, decades before clinical endpoints typically emerge, evidenced elevated dementia-risk scores (CAIDE, LIBRA, Lancet, ANU-ADRI, DunedinARB; β's 0.31-0.39) and displayed dementia-associated brain structural deficits and cognitive difficulties/decline., Discussion: Disadvantaged neighborhoods have more residents with dementia, and decades before dementia is diagnosed, residents have more dementia-risk factors and brain-structure antecedents. Whether or not neighborhoods causally influence risk, they may offer scalable opportunities for primary dementia prevention., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Importance: Mental health professionals typically encounter patients at 1 point in patients' lives. This cross-sectional window understandably fosters focus on the current presenting diagnosis. Research programs, treatment protocols, specialist clinics, and specialist journals are oriented to presenting diagnoses, on the assumption that diagnosis informs about causes and prognosis. This study tests an alternative hypothesis: people with mental disorders experience many different kinds of disorders across diagnostic families, when followed for 4 decades., Objective: To describe mental disorder life histories across the first half of the life course., Design, Setting, and Participants: This cohort study involved participants born in New Zealand from 1972 to 1973 who were enrolled in the population-representative Dunedin Study. Participants were observed from birth to age 45 years (until April 2019). Data were analyzed from May 2019 to January 2020., Main Outcomes and Measures: Diagnosed impairing disorders were assessed 9 times from ages 11 to 45 years. Brain function was assessed through neurocognitive examinations conducted at age 3 years, neuropsychological testing during childhood and adulthood, and midlife neuroimaging-based brain age., Results: Of 1037 original participants (535 male [51.6%]), 1013 had mental health data available. The proportions of participants meeting the criteria for a mental disorder were as follows: 35% (346 of 975) at ages 11 to 15 years, 50% (473 of 941) at age 18 years, 51% (489 of 961) at age 21 years, 48% (472 of 977) at age 26 years, 46% (444 of 969) at age 32 years, 45% (429 of 955) at age 38 years, and 44% (407 of 927) at age 45 years. The onset of the disorder occurred by adolescence for 59% of participants (600 of 1013), eventually affecting 86% of the cohort (869 of 1013) by midlife. By age 45 years, 85% of participants (737 of 869) with a disorder had accumulated comorbid diagnoses. Participants with adolescent-onset disorders subsequently presented with disorders at more past-year assessments (r = 0.71; 95% CI, 0.68 to 0.74; P < .001) and met the criteria for more diverse disorders (r = 0.64; 95% CI, 0.60 to 0.67; P < .001). Confirmatory factor analysis summarizing mental disorder life histories across 4 decades identified a general factor of psychopathology, the p-factor. Longitudinal analyses showed that high p-factor scores (indicating extensive mental disorder life histories) were antedated by poor neurocognitive functioning at age 3 years (r = -0.18; 95% CI, -0.24 to -0.12; P < .001), were accompanied by childhood-to-adulthood cognitive decline (r = -0.11; 95% CI, -0.17 to -0.04; P < .001), and were associated with older brain age at midlife (r = 0.14; 95% CI, 0.07 to 0.20; P < .001)., Conclusions and Relevance: These findings suggest that mental disorder life histories shift among different successive disorders. Data from the present study, alongside nationwide data from Danish health registers, inform a life-course perspective on mental disorders. This perspective cautions against overreliance on diagnosis-specific research and clinical protocols.

Importance: Lead is a neurotoxin with well-documented effects on health. Research suggests that lead may be associated with criminal behavior. This association is difficult to disentangle from low socioeconomic status, a factor in both lead exposure and criminal offending., Objective: To test the hypothesis that a higher childhood blood lead level (BLL) is associated with greater risk of criminal conviction, recidivism (repeat conviction), conviction for violent offenses, and variety of self-reported criminal offending in a setting where BLL was not associated with low socioeconomic status., Design, Setting, and Participants: A total of 553 individuals participated in a prospective study based on a population-representative cohort born between April 1, 1972, and March 31, 1973, from New Zealand; the Dunedin Multidisciplinary Health and Development Study observed participants to age 38 years (December 2012). Statistical analysis was performed from November 10, 2016, to September 5, 2017., Exposures: Blood lead level measured at age 11 years., Main Outcomes and Measures: Official criminal conviction cumulative to age 38 years (data collected in 2013), single conviction or recidivism, conviction for nonviolent or violent crime, and self-reported variety of crime types at ages 15, 18, 21, 26, 32, and 38 years., Results: Participants included 553 individuals (255 female and 298 male participants) who had their blood tested for lead at age 11 years. The mean (SD) BLL at age 11 years was 11.01 (4.62) μg/dL. A total of 154 participants (27.8%) had a criminal conviction, 86 (15.6%) had recidivated, and 53 (9.6%) had a violent offense conviction. Variety scores for self-reported offending ranged from 0 to 10 offense types at each assessment; higher numbers indicated greater crime involvement. Self-reported offending followed the well-established age-crime curve (ie, the mean [SD] variety of self-reported offending increased from 1.99 [2.82] at age 15 years to its peak of 4.24 [3.15] at age 18 years and 4.22 [3.02] at age 21 years and declined thereafter to 1.10 [1.59] at age 38 years). Blood lead level was a poor discriminator between no conviction and conviction (area under the curve, 0.58). Overall, associations between BLL and conviction outcomes were weak. The estimated effect of BLL was lower for recidivism than for single convictions and lower for violent offending than for nonviolent offending. Sex-adjusted associations between BLL reached statistical significance for only 1 of the 6 self-reported offending outcomes at age 15 years (r = 0.10; 95% CI, 0.01-0.18; P = .02)., Conclusions and Relevance: This study overcomes past limitations of studies of BLL and crime by studying the association in a place and time where the correlation was not confounded by childhood socioeconomic status. Findings failed to support a dose-response association between BLL and consequential criminal offending.