We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Accessibility at the Sterkfontein Caves UNESCO World Heritage Site limits public and scientific engagement. The authors digitally visualised part of the cave using laser scans and photogrammetry, geospatially integrating the digital cave and fossil datasets. This enables broader access for learners, educators and scientists and enhances scientific outreach potential.
We examine the optical counterparts of the 1 829 neutral hydrogen (H i) detections in three pilot fields in the Widefield ASKAP L-band Legacy All-sky Blind surveY (WALLABY) using data from the Dark Energy Spectroscopic Instrument (DESI) Legacy Imaging Surveys DR10. We find that 17% (315) of the detections are optically low surface brightness galaxies (LSBGs; mean g-band surface brightness within 1 $ R_e$ of $\gt 23$ mag arcsec$^{-2}$) and 3% (55) are optically ‘dark’. We find that the gas-rich WALLABY LSBGs have low star formation efficiencies, and have stellar masses spanning five orders of magnitude, which highlights the diversity of properties across our sample. 75% of the LSBGs and all of the dark H i sources had not been catalogued prior to WALLABY. We examine the optically dark sample of the WALLABY pilot survey to verify the fidelity of the catalogue and investigate the implications for the full survey for identifying dark H i sources. We assess the H i detections without optical counterparts and identify 38 which pass further reliability tests. Of these, we find that 13 show signatures of tidal interactions. The remaining 25 detections have no obvious tidal origin, so are candidates for isolated galaxies with high H i masses, but low stellar masses and star-formation rates. Deeper H i and optical follow-up observations are required to verify the true nature of these dark sources.
Common neuroanatomical regions are associated with both states of anorexia nervosa (AN) and autistic characteristics, but restoration of body mass index (BMI) has been associated with decreased presentation of autistic characteristics in some individuals with AN. This study aims to examine neuroanatomical correlates associated with autistic characteristics in those with acute anorexia nervosa (ac-AN) and those previously diagnosed with AN but whose weight has been restored (WR). In total, 183 individuals (healthy controls [HCs] = 67; n[ac-AN] = 68; n[WR] = 48) from the Brain imaging of Emotion And Cognition of adolescents with Anorexia Nervosa (BEACON) study were included, with autistic characteristics determined in both ac-AN and WR individuals (n = 116). To further examine BMI, ac-AN and WR group associations were compared. Random forest regression (RFR) models examined whether autistic characteristics and morphology of the anterior cingulate cortex (ACC), middle frontal gyrus (MFG), and orbitofrontal cortex (OFC) were able to predict future levels of social anhedonia and alexithymia. Group-wise differences were identified within the volume and surface area of the MFG and OFC, which were unrelated to BMI. Autistic characteristics were inversely associated with MFG and ACC volume, with differences in associations between ac-AN and WR groups seen in the surface area of the MFG. RFR models identified moderate-to-weak performance and found that autistic characteristics were not important predictive features in a priori and exploratory models. Findings suggest that the presence of autistic characteristics in those with ac-AN are associated with the volume of the MFG and are unrelated to BMI restoration.
The adoption of anaerobic digesters (ADs) and technologies stacked with them (AD+) has the potential to offer benefits to dairy producers and the environment. Production of biochar, hydrochar, and bioplastics can reduce greenhouse gas emissions, offer economic benefits to farmers through the sale of value-added products, reduce the need for fertilizer purchases, and promote a circular economy for dairy producers. We use a diffusion of innovations framework augmented to include economic, environmental, social, and regulatory considerations in addition to the operational aspects of the technologies. We conducted interviews with 21 participants representing for-profit, not-for-profit, governmental, and community service agencies in Idaho, the third-largest U.S. dairy state. Semi-structured interviews explored participants’ experiences with and perceptions of how relative advantage, compatibility, complexity, observability, trialability, environmental, economic, and social factors may facilitate or hinder the adoption of AD and three related emerging AD+ technologies. Interviews were analyzed using inductive coding and thematic analysis. Results show that participants were familiar with the need to address dairy manure waste and were interested in the potential benefits to farm revenue and the environment. However, the same factors associated with the relatively low adoption of AD in Idaho may also hinder the adoption of newer AD+ technologies. These include a lack of observability and trialability, installation and maintenance costs, access to technology, uncertain environmental impacts, unrealized economic benefits to dairy producers, and regulatory burden.
Objectives/Goals: Personalized cancer therapy based on genomic testing is advancing patient care. Genomic alterations in fibroblast growth factor receptor (FGFR) predict response to FGFR inhibitors; however, the role of RNA expression and protein activation is not known. We propose to examine the phospho-proteomic signature in FGFR-altered cancers to identify new candidates for FGFR-targeted therapies. Methods/Study Population: In our preliminary study, we have curated a cohort of FGFR2 mutants (13 FGFR2-fusions and 4 FGFR2 point mutations) with known clinical outcomes to FGFR inhibitors and 8 FGFR2 wild-type (WT) cholangiocarcinoma tumor samples to investigate the phospho-proteomic fingerprint using a clinical grade reverse phase protein array (RPPA). RPPAs are high throughput quantitative antibody-based proteomics assays that can quantify hundreds of proteins in thousands of patient tissues providing a high degree of sensitivity through laser tumor microdissection (LCM). We have selected proteins in the FGFR signaling pathway including FGFR2, AKT, ERK1.2, STAT1/3, FRS2, and PLCg to define the range of phospho-proteomic signal between FGFR2 WT and mutant cancers. All samples will undergo evaluation with RNASeq for gene expression. Results/Anticipated Results: Our initial analysis defined the range of RNA expression of FGFR2 and pFGFR2 protein signal (Y653/654 and Y769) between FGFR2 WT and FGFR2 mutant samples. On average, the FGFR2 mutant cohort displayed higher FGFR2 RNA expression compared to the FGFR2 WT cohort. There is no apparent correlation between RNA expression and clinical response to FGFR-targeted therapy. However, in this small cohort, there is no significant difference in FGFR2 phosphorylation between FGFR2 WT and mutant cancers. RPPA analysis of FGFR downstream signaling proteins reveals a wide range of phosphorylation, but no significant difference between FGFR2 WT and mutant cancers. Discussion/Significance of Impact: These findings illustrate the complexities of FGFR signaling between FGFR2 WT and mutant cancers. These data suggest that tumors with genomically WT FGFR may display increased pFGFR2 and downstream signaling phospho-proteins. We propose a larger study of cholangiocarcinoma to evaluate evidence of FGFR pathway activation in WT tumors.
In their 2022 publication in this journal, Suber and colleagues attempt to apply crime mapping to the illicit trade of cultural objects from the Middle East to establish a causal relationship between conflict and heritage looting. The article calls for comments by readers on the methodological approaches and results (p. 559). This commentary addresses the article’s shortcomings, specifically highlighting its inadequate grounding in existing literature, methodological limitations, and problematic data approach.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
COVID-19 vaccine effectiveness (VE) studies are limited in low- and middle-income countries. A case-control study was conducted among COVID-19 and other pneumonia patients admitted to a hospital in the Philippines during the pre-Omicron and Omicron periods. To elucidate factors associated with in-hospital death, 1782 COVID-19 patients were assessed. To estimate absolute VE for various severe outcomes, 1059 patients were assessed (869 [82.1%] COVID-19 cases; 190 [17.9%] controls). Factors associated with in-hospital death included older age, tuberculosis (adjusted odds ratio [aOR] 2.45 [95% confidence interval {95% CI} 1.69–3.57]), HIV (aOR 3.30 [95% CI 2.03–5.37]), and current smokers (aOR 2.65 [95% CI 1.72–4.10]). Pre-Omicron, the primary series provided high protection within a median of 2 months (hospitalization: 85.4% [95% CI 35.9–96.7%]; oxygen requirement: 91.0% [95% CI 49.4–98.4%]; invasive mechanical ventilation (IMV): 97.0% [95% CI 65.7–99.7%]; death: 96.5% [95% CI 67.1–99.6%]). During Omicron, the primary series provided moderate-high protection within a median of 6–9 months (hospitalization: 70.2% [95% CI 27.0–87.8%]; oxygen requirement: 71.4% [95% CI 29.3–88.4%]; IMV: 72.7% [95% CI −11.6–93.3%]; death: 58.9% [95% CI −82.8–90.8%]). Primary series VE against severe COVID-19 outcomes was consistently high for both pre-Omicron and Omicron in a setting where approximately half of the vaccinees received inactivated vaccines.
Tape rolls are often used for multiple patients despite recommendations by manufacturers for single-patient use. We developed a survey to query Health Care Personnel about their tape use practices and beliefs and uncovered behaviors that put patients at risk for hospital-acquired infections due to tape use.
Evidence-based insertion and maintenance bundles are effective in reducing the incidence of central line-associated bloodstream infections (CLABSI) in intensive care unit (ICU) settings. We studied the adoption and compliance of CLABSI prevention bundle programs and CLABSI rates in ICUs in a large network of acute care hospitals across Canada.
There is a high incidence of serious mental illness (SMI) and antipsychotic use in the respiratory high dependence unit (HDU) compared with the general population. However, there is a paucity of data in the extant literature evaluating the relationships between respiratory failure and antipsychotics.
Aims
To investigate the relationship between antipsychotics and respiratory failure in people admitted to a respiratory HDU, and to gain a better understanding of the potential impact of antipsychotic medications on respiratory outcomes.
Method
Medical, demographic and clinical outcome data were collected for a consecutive sample of 638 individuals admitted to a respiratory HDU between the dates 1 January 2018 and 29 May 2021 at a large quaternary hospital.
Results
Multivariate models controlling for confounders found that antipsychotic medications increased risk of admission for type 2 respiratory failure and chronic obstructive pulmonary disease exacerbation without hypercapnia by 3.7 and 11.45 times, respectively. For people admitted with type 2 respiratory failure, antipsychotic use increased the risk of requiring non-invasive ventilation by 4.9 times. Those prescribed an antipsychotic were more likely to be readmitted within 30 days. Over 30% of individuals were prescribed antipsychotics for an unlicensed indication.
Conclusions
Poor respiratory outcomes may be a previously unknown adverse drug reaction of antipsychotics. Modifications to clinical care and clinical pathways for those with SMI prescribed antipsychotic medications, including optimising their chronic health and deprescribing where appropriate, should be prioritised.
Racial and ethnic variations in antibiotic utilization are well-reported in outpatient settings but little is known about inpatient settings. Our objective was to describe national inpatient antibiotic utilization among children by race and ethnicity.
Methods:
This study included hospital visit data from the Pediatric Health Information System between 01/01/2022 and 12/31/2022 for patients <20 years. Primary outcomes were the percentage of hospitalization encounters that received an antibiotic and antibiotic days of therapy (DOT) per 1000 patient days. Mixed-effect regression models were used to determine the association of race-ethnicity with outcomes, adjusting for covariates.
Results:
There were 846,530 hospitalizations. 45.2% of children were Non-Hispanic (NH) White, 27.1% were Hispanic, 19.2% were NH Black, 4.5% were NH Other, 3.5% were NH Asian, 0.3% were NH Native Hawaiian/Other Pacific Islander (NHPI) and 0.2% were NH American Indian. Adjusting for covariates, NH Black children had lower odds of receiving antibiotics compared to NH White children (aOR 0.96, 95%CI 0.94–0.97), while NH NHPI had higher odds of receiving antibiotics (aOR 1.16, 95%CI 1.05–1.29). Children who were Hispanic, NH Asian, NH American Indian, and children who were NH Other received antibiotic DOT compared to NH White children, while NH NHPI children received more antibiotic DOT.
Conclusions:
Antibiotic utilization in children’s hospitals differs by race and ethnicity. Hospitals should assess policies and practices that may contribute to disparities in treatment; antibiotic stewardship programs may play an important role in promoting inpatient pharmacoequity. Additional research is needed to examine individual diagnoses, clinical outcomes, and drivers of variation.
Oceania is currently facing a substantial challenge: to provide sustainable and ethical food systems that support nutrition and health across land and water. The Nutrition Society of Australia and the Nutrition Society of New Zealand held a joint 2023 Annual Scientific Meeting on ‘Nutrition and Wellbeing in Oceania’ attended by 408 delegates. This was a timely conference focussing on nutrition challenges across the Pacific, emphasising the importance of nutrition across land and water, education settings, women’s health and gut health. Cutting-edge, multi-disciplinary and collaborative research was presented in a 4-day programme of keynote presentations, workshops, oral and poster sessions, breakfast and lunch symposiums and early career researcher sessions. The conference highlighted the importance of collaboration between nations to address the challenge facing nutrition and wellbeing across Oceania. A systems approach of collaboration among scientists, industry and government is vital for finding solutions to this challenge.
Pragmatic trials aim to speed translation to practice by integrating study procedures in routine care settings. This study evaluated implementation outcomes related to clinician and patient recruitment and participation in a trial of community paramedicine (CP) and presents successes and challenges of maintaining pragmatic study features.
Methods:
Adults in the pre-hospital setting, emergency department (ED), or hospital being considered for referral to the ED/hospital or continued hospitalization for intermediate-level care were randomized 1:1 to CP care or usual care. Referral and enrollment data were tracked administratively, and patient characteristics were abstracted from the electronic health record (EHR). Enrolled patients completed baseline surveys, and a subset of intervention patients were interviewed. All CPs and a sample of clinicians and administrators were invited to complete a survey and interview.
Results:
Between January 2022 and February 2023, 240 enrolled patients (42% rural) completed surveys, and 22 completed an interview; 63 staff completed surveys and 20 completed an interview. Ninety-three clinicians in 27 departments made at least one referral. Factors related to referrals included program awareness and understanding the CP practice scope. Most patients were enrolled in the hospital, but characteristics were similar to the primary care population and included older and medically complex patients. Challenges to achieving representativeness included limited EHR infrastructure, constraints related to patient consenting, and clinician concerns about patient randomization disrupting preferred care.
Conclusion:
Future pragmatic trials in busy clinical settings may benefit from regulatory policies and EHR capabilities that allow for real-world study conduct and representative participation. Trial registration: NCT05232799.
Young people from racialised backgrounds are overrepresented in justice services. This study explored differences in community support offered to young people from racialised groups referred to a forensic child and adolescent mental health service.
Method
We compared support offered to 427 young people, according to five ethnic groups.
Results
Over 20% of young people referred were Black (compared with 14% of the local population) and 15.8% were Dual White and Black Heritage (compared with 4% of the local population). Odds ratios showed that Black and Dual Heritage groups were more frequently involved with youth offending services (Black: 2.59, Dual Heritage: 2.88), gangs services (Black: 4.31, Dual Heritage: 7.13) and have a national referral mechanism (Black: 3.61, Dual Heritage: 4.01) than their White peers, but were less often in mainstream education compared with their Asian peers (Black: 0.26, Dual Heritage: 0.29). Black (odds ratio 0.35) and Dual Heritage (odds ratio 0.40) young people were less frequently diagnosed with a neurodevelopmental disorder than their White peers.
Conclusions
Those from Black and Dual Heritage backgrounds were disproportionately disadvantaged.
In December 2018, an outbreak of Salmonella Enteritidis infections was identified in Canada by whole-genome sequencing (WGS). An investigation was initiated to identify the source of the illnesses, which proved challenging and complex. Microbiological hypothesis generation methods included comparisons of Salmonella isolate sequence data to historical domestic outbreaks and international repositories. Epidemiological hypothesis generation methods included routine case interviews, open-ended centralized re-interviewing, thematic analysis of open-ended interview data, collection of purchase records, a grocery store site visit, analytic comparison to healthy control groups, and case–case analyses. Food safety hypothesis testing methods included food sample collection and analysis, and traceback investigations. Overall, 83 cases were identified across seven provinces, with onset dates from 6 November 2018 to 7 May 2019. Case ages ranged from 1 to 88 years; 60% (50/83) were female; 39% (22/56) were hospitalized; and three deaths were reported. Brand X profiteroles and eclairs imported from Thailand were identified as the source of the outbreak, and eggs from an unregistered facility were hypothesized as the likely cause of contamination. This study aims to describe the outbreak investigation and highlight the multiple hypothesis generation methods that were employed to identify the source.
Declining labor force participation of older men throughout the 20th century and recent increases in participation have generated substantial interest in understanding the effect of public pensions on retirement. The National Bureau of Economic Research's International Social Security (ISS) Project, a long-term collaboration among researchers in a dozen developed countries, has explored this and related questions. The project employs a harmonized approach to conduct within-country analyses that are combined for meaningful cross-country comparisons. The key lesson is that the choices of policy makers affect the incentive to work at older ages and these incentives have important effects on retirement behavior.