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Some of us recently discussed the problems existing in describing the channels that permit interventricular shunting. We offered suggestions for improvement, particularly when assessing the channel that is found when both arterial trunks arise from the morphologically right ventricle. Our proposals engendered significant debate, with several criticisms appearing in an editorial commentary. The commentator now accepts that not all of the criticisms were justified. In an attempt to seek further consensus, we have now joined with additional colleagues so as to clarify the aspects of our initial work that created potential confusion. Having reviewed the aspects producing the misconceptions, we again provide an overview of the evidence relevant to deficient ventricular septation now provided by knowledge of cardiac development. We show how remodelling of the primary interventricular communication involves the provision of an inlet for the developing right ventricle and an outlet for the developing right ventricle. During this process, the secondary interventricular foramen, which is a subaortic-left ventricular communication when the outflow tract remains supported exclusively by the right ventricle, becomes the outflow tract for the left ventricle, with a subaortic-right ventricular communication then being closed to complete ventricular septation. We show how knowledge of these processes, coupled with an appreciation of the mechanism of formation of the muscular ventricular septum and the separate formation of an embryonic muscular outlet septum, which with normal development becomes the subpulmonary infundibulum, provides the basis for understanding the various phenotypic lesions that permit interventricular shunting in the postnatal heart.
On November 20, 2021, petroleum fuel contaminated the Red Hill well, which provides water to about 93 000 persons on Oahu, Hawaii. Initial investigations recommended further evaluations of long-term health effects of petroleum exposure in drinking water. We reviewed electronic health records of those potentially exposed to contaminated water to understand prevalence of conditions and symptoms.
Methods
A sample of persons potentially exposed during November 20, 2021-March 18, 2022 who sought care within the military health system through February 24, 2023 was identified. Abstracted records were categorized as worsening preexisting or persistent new for conditions and symptoms.
Results
Of 653 medical charts reviewed, 357 (55%) had worsening preexisting or persistent new conditions or symptoms. Most-documented conditions included worsening preexisting migraine (8%; 50/653) and chronic pain (4%; 26/653), and persistent new migraine (2%; 14/653) and adjustment disorder (2%; 13/653). Most-documented symptoms included worsening preexisting headache (8%; 49/653) and anxiety (6%; 42/653), and persistent new rash (7%; 46/653) and headache (5%; 34/653).
Conclusions
Approximately half of the abstracted medical records demonstrated worsening preexisting or persistent new conditions or symptoms and might benefit from sustained access to physical, mental, and specialized health care support systems. Continued monitoring for long-term health outcomes is recommended.
Functional impairment in daily activities, such as work and socializing, is part of the diagnostic criteria for major depressive disorder and most anxiety disorders. Despite evidence that symptom severity and functional impairment are partially distinct, functional impairment is often overlooked. To assess whether functional impairment captures diagnostically relevant genetic liability beyond that of symptoms, we aimed to estimate the heritability of, and genetic correlations between, key measures of current depression symptoms, anxiety symptoms, and functional impairment.
Methods
In 17,130 individuals with lifetime depression or anxiety from the Genetic Links to Anxiety and Depression (GLAD) Study, we analyzed total scores from the Patient Health Questionnaire-9 (depression symptoms), Generalized Anxiety Disorder-7 (anxiety symptoms), and Work and Social Adjustment Scale (functional impairment). Genome-wide association analyses were performed with REGENIE. Heritability was estimated using GCTA-GREML and genetic correlations with bivariate-GREML.
Results
The phenotypic correlations were moderate across the three measures (Pearson’s r = 0.50–0.69). All three scales were found to be under low but significant genetic influence (single-nucleotide polymorphism-based heritability [h2SNP] = 0.11–0.19) with high genetic correlations between them (rg = 0.79–0.87).
Conclusions
Among individuals with lifetime depression or anxiety from the GLAD Study, the genetic variants that underlie symptom severity largely overlap with those influencing functional impairment. This suggests that self-reported functional impairment, while clinically relevant for diagnosis and treatment outcomes, does not reflect substantial additional genetic liability beyond that captured by symptom-based measures of depression or anxiety.
This systematic review aimed to analyze studies assessing the extent to which General Practitioners (GPs) engage patients in the decision-making process during consultations.
Background:
Shared Decision Making (SDM) stands at the core of patient-centred care, particularly in primary healthcare, where a diverse array of medical decisions transpires. In a 2015 systematic review summarizing studies on the Observing Patient Involvement in Decision Making (OPTION) instrument to assess SDM objectively across healthcare settings, a notable dearth of patient involvement was observed.
Methods:
A comprehensive literature search encompassing three digital databases was conducted up to November 2023. Inclusion criteria focused on studies employing a comparative study design, centric to primary healthcare, and utilizing the OPTION-5 or -12 instrument to gauge SDM levels. Two investigators independently performed study selection, risk of bias assessment, and data extraction using a list of predefined variables, with discrepancies resolved by a third reviewer. PROSPERO registration-ID: CRD42023475419.
Findings:
Initially, harvesting 447 articles, our review retained 29 studies published between 2003 and 2022. Mean age of GPs was 45.5 (range 33–53) years. Reported baseline OPTION scores varied between 1.5 and 57.2 on a 0–100-point scale, with a median score of 16. Following SDM interventions, OPTION-scores increased significantly to a median of 28.5, range 16–83.
Conclusion:
The overall level of SDM among GPs remains relatively low and has shown minimal improvement over the past decade. However, interventions promoting SDM appear to enhance patient involvement levels. This underscores the necessity for increased education and tools, directed at GPs and patients, to foster and elevate the practice of SDM.
Global efforts to combat micronutrient deficiencies have often focused on assessing nutrient intakes and supplies(1,2), yet no studies have explored the role of crop selection and land suitability to tackle these deficiencies. This study aims to bridge this gap using existing estimates of global prevalence of iron(3) and zinc(4) deficiencies to identify crops with the highest potential to mitigate these deficiencies. Using the USDA food composition database, we established nutrient profiles for 37 widely cultivated crops, focusing on their iron and zinc content per 100 grams. To evaluate these crops’ effectiveness to meet nutrient requirements, we compared compositions to Harmonized Average Requirements (H-ARs) for women of reproductive age (WRA), a group particularly vulnerable to micronutrient deficiencies. The H-ARs account for variations in nutrient absorption and bioavailability(5). For each crop, we calculated the percentage of the H-AR met by 100 grams of iron and zinc content. This percentage was adjusted for the global prevalence of iron and zinc deficiencies by introducing deficiency weighting—multiplying each crop’s nutrient contributions by the global prevalence of iron and zinc deficiencies. The result was a deficiency-weighted nutrient score for each crop. Soybeans scored highest at 61.67, followed by cowpeas (50.30), pearl millet (33.69), and Phaseolus beans (31.33), indicating their strong potential to address global iron and zinc deficiencies. Next, we integrated these nutrient scores with global land suitability and yield potential data from the Global Agro-Ecological Zones (GAEZ) database to map regions most suited for growing these nutrient-dense crops. On average, our findings show that Tonga is the most suitable country for soybean cultivation, with a potential yield of 3.77 tons per hectare (tons/ha), Uruguay for cowpeas (2.82 tons/ha), Lithuania for Phaseolus beans (3.93 tons/ha), and Guinea-Bissau for pearl millet (3.87 tons/ha). Through multivariate clustering, we linked global deficiency patterns with yield potential across various regions. Countries such as those in the Caribbean, Eastern, Western, and Middle Africa, and Southern and Southeastern Asia emerged as priority regions where the production of these crops would be most beneficial to combat iron and zinc deficiencies. The results provide valuable insights to align agricultural land use practice with nutritional requirements, particularly in regions with high iron and zinc deficiency prevalence.
The World Health Organization (WHO) has a global initiative to eliminate industrially produced trans fatty acids (iTFAs) from the food supply (1). Formed via the partial hydrogenation of vegetable oils to create hardened vegetable fat, iTFAs can be found in processed foods including fried foods and baked goods. Even small amounts of iTFAs can increase the risk of coronary heart disease. These can be successfully eliminated from the food supply with the WHO recommending a ban on partially hydrogenated oils or to limit iTFA in food to a maximum of 2% of total fat (1). As of June 2024, over 50 countries had one of these regulatory measures in place. The trans-Tasman Food Regulation System is considering policy options to ensure iTFAs are eliminated or reduced as much as possible from the food supply in Australia and New Zealand. Up to date data on the presence of iTFAs in the New Zealand food supply is needed to inform this work as this was last measured in New Zealand in 2007/09 for packaged food and 2013 for fast food. The aim of this survey was to determine the presence and levels of iTFAs in the New Zealand food supply. Since it is not possible to analytically quantify iTFA separately from trans-fats that occur naturally in food products of ruminant origin, such as dairy, beef and lamb products, the sampling plan was designed to target products likely to contain predominately iTFA and adapted from the WHO global protocol for measuring trans fatty acid profiles of foods(2) to the New Zealand context. The survey analysed the trans-fat content of 627 products across national supermarkets (275 products), international supermarkets specialising in imported foods (149 products) and ready-to-eat food outlets (203 products from three regions). One hundred and six products (16.9%) contained trans-fat that exceeded 2% of total fat. Twenty-five (4%) of these products were likely to contain predominately iTFA. The 25 products predominately containing iTFA included eight products from national supermarkets (mostly bakery products), nine products from international supermarkets (mostly curry pastes and biscuits) and eight products from ready-to-eat food outlets (all fried foods). The median trans-fat content of these 25 products was 3.2% of total fat (assumed to be all iTFA). Over a third of these products contained more than double the recommended WHO limit, with five products containing over four times the limit and one product containing more than 16 times the WHO limit. The remaining 81 products may contain some iTFA, but we were unable to quantify the amount. The results from this survey will be used by New Zealand Food Safety to inform the consideration of regulatory options for reducing iTFAs in foods in New Zealand.
Comprehensive cognitive remediation improves cognitive and functional outcomes in people with serious mental illness, but the specific components required for effective programs are uncertain. The most common methods to improve cognition are facilitated computerized cognitive training with coaching and teaching cognitive self-management strategies. We compared these methods by dismantling the Thinking Skills for Work program, a comprehensive, validated cognitive remediation program that incorporates both strategies.
Methods
In a randomized controlled trial we assigned 203 unemployed people with serious mental illness in supported employment programs at two mental health agencies to receive either the full Thinking Skills for Work (TSW) program, which included computerized cognitive training (based on Cogpack software), or the program with cognitive self-management (CSM) but no computer training. Outcomes included employment, cognition, and mental health over 2 years. To benchmark outcomes, we also examined competitive work outcomes in a similar prior trial comparing the TSW program with supported employment only.
Results
The TSW and CSM groups improved significantly on all outcomes, but there were no differences between the groups. Competitive work outcomes for both groups resembled those of the TSW program in a prior trial and were better than the supported employment-only group in that study, suggesting that participants in both groups benefited from cognitive remediation.
Conclusions
Providing facilitated computerized cognitive training improved neither employment nor cognitive outcomes beyond teaching cognitive self-management strategies in people receiving supported employment. Computerized cognitive training may not be necessary for cognitive remediation programs to improve cognitive and functional outcomes.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
A variety of larvae and parthenitae of trematodes have been detected in gastropods in the intertidal zone in Japan. However, because of the difficulty associated with the morphological identification of these stages, they have rarely been identified to the species or higher taxonomic levels. In this study, trematodes of these stages were sampled from intertidal gastropods in the Japanese coastal regions and were identified to the species, genus, or family levels morphologically and molecularly to elucidate or predict their life cycles. Investigation of 17 gastropod species (682 individuals in total) from 14 localities led to the detection of trematodes in 47 individuals belonging to six snail species. The infected gastropods were morphologically identified as Nipponacmea fuscoviridis, Monodonta confusa, Trochus sacellum, Batillaria attramentaria, Littorina brevicula, and Purpuradusta gracilis. Our molecular analyses revealed that sporocysts, rediae, and metacercariae from the gastropods were divided into 14 species belonging to nine families: Philophthalmidae, Fellodistomidae, Gymnophallidae, Lepocreadiidae, Heterophyidae, Opisthorchiidae, Notocotylidae, Microphallidae, and Opecoelidae. These trematodes were thought to use fishes, octopuses, seabirds, and marine mammals as their definitive hosts. Marine organisms such as jellyfishes, crustaceans, and fishes are also thought to act as the second intermediate and paratenic hosts of few present trematode species. As for the other trematode species, DNA barcodes of trematodes from various marine organisms will also illuminate the life cycles in future.
A new model is presented for the decay of plane shock waves in equilibrium flows with an arbitrary equation of state. A fundamental challenge for the accurate prediction of shock propagation using analytical modelling is to account for the coupling between a shock’s motion and the post-shock flow. Our model accomplishes this by neglecting only higher-order perturbations to the second velocity gradient, $u_{xx}$, in the incident simple wave. The second velocity gradient is generally small and exactly zero for centred expansion waves in a perfect gas, so neglecting its effect on the shock motion provides an accurate closure criterion for a shock-change equation. This second-order shock-change equation is derived for a general equation of state. The model is tested by comparison with numerical simulations for three problems: decay by centred waves in a perfect gas, decay by centred waves in equilibrium air and decay by the simple wave generated from the constant deceleration of piston in a perfect gas. The model is shown to be exceptionally accurate for a wide range of conditions, including small $\gamma$ and large shock Mach numbers. For a Mach 15 shock in equilibrium air, model errors are less than 2 % in the first 60 % of the shock’s decay. The analytical results possess a simple formulation but are applicable to fluids with a general equation of state, enabling new insight into this fundamental problem in shock wave physics.
Background: Epstein-Barr virus (EBV) infection is believed to be a critical prerequisite for the development of multiple sclerosis (MS). This study aims to investigate whether anti-EBV titres are elevated before the onset of MS symptoms in people with radiologically isolated syndrome (pwRIS) and to evaluate their association with markers of adverse clinical outcomes. Methods: Epstein-Barr nuclear antigen 1 (EBNA1) and viral capsid antigen (VCA) titres were quantified in a cohort of 47 pwRIS and 24 healthy controls using Enzyme-Linked Immuno-Sorbent Assay. Plasma glial fibrillary acidic protein (GFAP) and neurofilament light protein (NfL) were measured using single-molecule array. MRI lesion metrics and the development of MS symptoms over time were also evaluated. Results: EBNA1 titres were higher pwRIS compared to healthy controls (p=0.038), while VCA titres were not (p=0.237). A positive correlation was observed between EBNA1 titres and plasma GFAP in pwRIS (p=0.005). Neither EBNA1 nor VCA titres correlated with NfL. MRI lesion measures and the development of MS symptoms did not show any significant relationship with EBNA1 or VCA titres. Conclusions: Eelevated EBNA1 titres are detectable prior to MS symptom onset and correlate with GFAP, a biomarker associated with worse clinical outcomes. However, their role in disease progression and clinical outcomes requires further investigation.
Background: Non-pharmacological interventions that promote self-management are crucial for individuals with mild cognitive impairment (MCI.) Mindfulness training has shown promise but is often not tailored to MCI. Methods: In 2021, the Neil and Susan Manning Cognitive Health Initiative (CHI) - a collaboration between the Vancouver Island Health Authority, Universities of BC and Victoria, and the Victoria Hospitals Foundation - partnered with the BC Association for Living Mindfully (BCALM) to develop a specialized mindfulness program for MCI, based on Mindfulness-Based Stress Reduction (MBSR). This multi-phase initiative aimed to enhance self-management, address the lack of outpatient services for MCI in Victoria, and contribute to the evidence base for mindfulness interventions. Results: Phase 1 assessed the BCALM program’s suitability for MCI; feedback included suggestions to simplify content and meditations. Phase 2 piloted an adapted version, with an 8-week program consisting of weekly sessions. Participants, recruited from the Seniors Outpatient Clinic in Victoria, completed pre- and post-program surveys; results showed over 90% of participants reported improved memory and coping, and 80% managed memory-related challenges better. Conclusions: Now in Phase 3, the MCI program is being transitioned into regular BCALM curriculum, with plans for a clinical trial comparing it to traditional psychoeducational approaches.
Background: In multiple sclerosis (MS), soluble mediators of neuroinflammation are released by activated lymphocytes and resident immune cells, leading to demyelination and neurodegeneration. Radiologically isolated syndrome (RIS) is an entity in which white matter lesions fulfilling criteria for MS occur in individuals without any suggestive symptoms. The exact nature of pro- and anti-inflammatory cytokines in blood, and their association with disease activity in RIS/MS requires further clarification. Methods: Plasma was collected and cryopreserved from healthy controls (HCs), people with RIS and relapsing-remitting MS (RRMS) at the Barlo MS Centre. All samples were analyzed with OLink Target 96 Inflammation Multiplex Immunoassay Panel. Results: Individuals with RIS (p=0.0001; p= 0.0007; p= 0.0012) and RRMS (p<0.0001; p= 0.0003; p= 0.00112) had significantly higher concentrations of hepatocyte growth factor (HGF), interleukin-6 (IL-6), and chemokine ligand 23 (CCL23) in plasma compared to HCs, and patients with RRMS (p=0.0087) had significantly higher concentrations of HGF compared to individuals with RIS. Conclusions: Our study demonstrates that HGF, IL-6 and CCL23 are significantly increased in the plasma of patients with RIS and RRMS compared to HCs. Our observations suggest that the biology of MS is present in those with RIS, and these neuroinflammatory mediators may serve as a biomarker of disease activity.
Background: Electroencephalography (EEG) has emerged as a minimally invasive technique to quantify functional changes in neural activity associated with neurodegenerative disorders such as Alzheimer’s Disease (AD). Given its non-invasive approach, EEG has the potential to fill the pressing gap forearly, accurate, and accessible methods to detect and characterize disease progression in AD. Methods: To address these challenges, we conducted a pilot analysis of a custom machine learning-based automated preprocessing and feature extraction pipeline to identify indicators of AD and correlates of disease progression. Results: Our pipeline successfully detected several new and previously established EEG-based measures indicative of AD status and progression. Key findings included alterations in delta and theta band power, network connectivity disruptions, and increased slowing of brain rhythms. Additionally, we observed strong correlations between EEG-derived metrics and clinical measures such as Mini-Mental State Examination (MMSE) scores, supporting the external validity of our approach. These findings highlight the sensitivity of EEG biomarkers in differentiating between early and late stages of AD. Conclusions: Our findings suggest that this automated approach provides a promising initial framework for implementing EEG biomarkers in the AD patient population, paving the way for improved diagnostic and monitoring strategies.
Depression, a leading cause of global disability, arises from a multifaceted combination of genetic and environmental components. This study explores the relationship between major depressive disorder (MDD) polygenic scores (PGS), characteristics and symptoms of depression, and community-shared socioeconomic factors derived from postal code data in a cohort of 12,646 individuals from the Australian Genetics of Depression Study (AGDS). Our findings reveal that people living in areas with relatively higher socioeconomic advantages and education/occupation scores are more likely to report experiencing fewer depressive symptoms during their worst depressive period, as well as fewer number of lifetime episodes. Additionally, participants who reported depression onset later in life tend to currently reside in wealthier areas. Interestingly, no significant interaction between genetic and socioeconomic factors was observed, suggesting their independent contribution to depression outcomes. This research underscores the importance of integrating socioeconomic factors into psychiatric evaluation and care, and points to the critical role of public policy in addressing mental health disparities driven by socioeconomic factors. Future research should aim to further elucidate the causal relationships within these associations and explore the potential for integrated genetic and socioeconomic approaches in mental health interventions.
This study evaluated Medicaid claims (MC) data as a valid source for outpatient antimicrobial stewardship programs (ASPs) by comparing it to electronic medical record (EMR) data from a single academic center.
Methods:
This retrospective study compared pediatric patients’ MC data with EMR data from the Marshall Health Network (MHN). Claims were matched to EMR records based on patient Medicaid ID, service date, and provider NPI number. Demographics, antibiotic choice, diagnosis appropriateness, and guideline concordance were assessed across both data sources.
Setting:
The study was conducted within the MHN, involving multiple pediatric and family medicine outpatient practices in West Virginia, USA.
Patients:
Pediatric patients receiving care within MHN with Medicaid coverage.
Results:
MC and EMR data showed >90% agreement in antibiotic choice, gender, and date of service. Discrepancies were observed in diagnoses, especially for visits with multiple infectious diagnoses. MC data demonstrated similar accuracy to EMR data in identifying inappropriate prescriptions and assessing guideline concordance. Additionally, MC data provided timely information, enhancing the feasibility of impactful outpatient ASP interventions.
Conclusion:
MC data is a valid and timely resource for outpatient ASP interventions. Insurance providers should be leveraged as key partners to support large-scale outpatient stewardship efforts.