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.
Single ventricle patients undergoing comprehensive stage II palliation have higher incidence of severe acute kidney injury compared to the bidirectional Glenn palliation; however, the optimal method for early detection remains unknown. Several urinary biomarkers are increased in other patient populations with postoperative kidney injury. We explored the kinetics of these biomarkers in this high-risk population.
We conducted prospective, observational study of 20 patients with single ventricle physiology who underwent second stage palliation (July 2019–December 2021). Acute kidney injury was defined by Kidney Diseases Improving Global Guidelines, based on peak serum creatinine value and urine output. Urine samples were collected pre-operatively and at 1-, 6-, and 24-hours post-surgery. Urinary biomarkers neutrophil gelatinase-associated lipocalin, interleukin-18, liver fatty acid-binding protein, kidney injury molecule-1, and cystatin C were quantified by enzyme linked immunosorbent assay, normalised to urinary creatinine, and shown as median [interquartile range].
Four patients (50%) undergoing comprehensive stage II and 1 patient (8%) undergoing bidirectional Glenn palliation developed stage ≥ 2 acute kidney injury. Comprehensive stage II compared to bidirectional Glenn group had higher median neutrophil gelatinase-associated lipocalin (1769 [1309–1961] versus 91[18–1120] ng/mg) and liver fatty acid-binding protein (12,836 [5016–19798] versus 1272 [220–5172] ng/mg) that peaked 1-hour post-surgery. Kidney injury molecule-1 was significantly greater at 1-, 6-, and 24-hours (greatest) post-surgery in comprehensive stage II than bidirectional Glenn (24h: 11[9–23]) versus 2 [1–6] ng/mg).
Elevated urinary neutrophil gelatinase-associated lipocalin, liver fatty acid-binding protein, and kidney injury molecule-1 may be useful biomarkers for early detection of acute kidney injury in children following comprehensive stage II palliation.
Objectives/Goals: One in 14 individuals have a substance use disorder (SUD). We suggest that a trait of poor impulse control, or high impulsivity, may predict relapse risk. We explore how changes in brain structure linked to decision-making and reward might drive high impulsivity, helping create a “biosignature” to identify those most at risk and guide treatment choices. Methods/Study Population: Male rats were phenotyped as high impulsive (HI) or low impulsive (LI) based on premature responses on the one-choice serial reaction time (1-CSRT) task. Rats then received an intracranial infusion of a retrograde virus (AAVr2) in the nucleus accumbens (NAc) to trace corticoaccumbens neurons back to the medial prefrontal cortex (mPFC). After impulsivity phenotyping (ITI8), another cohort of animals performed cocaine self-administration followed by 30 days of abstinence. Cue reactivity, a measure of relapse-like behaviors, was performed on abstinence day 30. Analyses of microtubule-associated protein 2 (MAP2), a cytoskeletal marker of dendrites, spines, and somas was performed with western blotting and fluorescent images of brain slices after phenotyping and cocaine abstinence. Results/Anticipated Results: HI rats made greater premature responses, a marker of impulsive action vs. LI rats at baseline (p Discussion/Significance of Impact: Poor inherent impulse control and drug cues heighten relapse risk. We found high impulsivity linked to brain structure differences and lower protein markers of synaptic (units supporting signaling) strengthening. Future investigations into brain-behavior links with impulsivity may further identify a SUD relapse vulnerability biosignature.
People with psychosis experience worse cardiometabolic health than the same-aged general population. In New Zealand, Indigenous Māori experiencing psychosis have greater risk of cardiometabolic and other physical health problems.
Aims
To identify a cohort of adults accessing secondary mental health and addiction services in New Zealand, with a previous psychosis diagnosis as of 1 January 2018, and compare odds of hospital admission outcomes, mortality and receipt of cardiometabolic blood screening between Māori and non-Māori in the following 2 years.
Method
Crude and adjusted logistic regression models compared odds of hospital admission outcomes, mortality and receipt of cardiometabolic blood screening (lipids and haemoglobin A1c) between Māori and non-Māori, occurring between 1 January 2018 and 31 December 2019.
Results
A cohort (N = 21 214) of Māori (n = 7274) and non-Māori (n = 13 940) was identified. Māori had higher adjusted risk of mortality (odds ratio 1.26, 95% CI 1.03–1.54), and hospital admission with diabetes (odds ratio 1.64, 95% CI 1.43–1.87), cardiovascular disease (odds ratio 1.54, 95% CI 1.25–1.88) and any physical health condition (odds ratio 1.07, 95% CI 1.00–1.15) than non-Māori. Around a third of people did not receive recommended cardiometabolic blood screening, with no difference between Māori and non-Māori after covariate adjustment.
Conclusions
Māori experiencing psychosis are more likely to die and be admitted to hospital with cardiovascular disease or diabetes than non-Māori. Because of the higher cardiometabolic risk borne by Māori, it is suggested that cardiometabolic screening shortfalls will lead to worsening physical health inequities for Māori experiencing psychosis.
Few studies have examined the genetic population structure of vector-borne microparasites in wildlife, making it unclear how much these systems can reveal about the movement of their associated hosts. This study examined the complex host–vector–microbe interactions in a system of bats, wingless ectoparasitic bat flies (Nycteribiidae), vector-borne microparasitic bacteria (Bartonella) and bacterial endosymbionts of flies (Enterobacterales) across an island chain in the Gulf of Guinea, West Africa. Limited population structure was found in bat flies and Enterobacterales symbionts compared to that of their hosts. Significant isolation by distance was observed in the dissimilarity of Bartonella communities detected in flies from sampled populations of Eidolon helvum bats. These patterns indicate that, while genetic dispersal of bats between islands is limited, some non-reproductive movements may lead to the dispersal of ectoparasites and associated microbes. This study deepens our knowledge of the phylogeography of African fruit bats, their ectoparasites and associated bacteria. The results presented could inform models of pathogen transmission in these bat populations and increase our theoretical understanding of community ecology in host–microbe systems.
An alternative surgical approach for hypoplastic left heart syndrome is the Hybrid pathway, which delays the risk of acute kidney injury outside of the newborn period. We sought to determine the incidence, and associated morbidity, of acute kidney injury after the comprehensive stage 2 and the cumulative incidence after the first two operations in the Hybrid pathway.
Design:
A single centre, retrospective study was conducted of hypoplastic left heart patients completing the second-stage palliation in the Hybrid pathway from 2009 to 2018. Acute kidney injury was defined utilising Kidney Diseases Improving Global Outcomes criteria. Perioperative and post-operative characteristics were analysed.
Results:
Sixty-one patients were included in the study cohort. The incidence of acute kidney injury was 63.9%, with 36.1% developing severe injury. Cumulatively after the Hybrid Stage 1 and comprehensive stage 2 procedures, 69% developed acute kidney injury with 36% developing severe injury. The presence of post-operative acute kidney injury was not associated with an increase in 30-day mortality (acute kidney injury 7.7% versus none 9.1%; p = > 0.9). There was a significantly longer median duration of intubation among those with acute kidney injury (acute kidney injury 32 (8, 155) hours vs. no injury 9 (0, 94) hours; p = 0.018).
Conclusions:
Acute kidney injury after the comprehensive stage two procedure is common and accounts for most of the kidney injury in the first two operations of the Hybrid pathway. No difference in mortality was detected between those with acute kidney injury and those without, although there may be an increase in morbidity.
Background: A subset of patients experience poor outcomes following anterior cervical discectomy and fusion (ACDF). Our study aimed to identify postoperative trajectories of disability, neck/arm pain and determine baseline measures that predict subgroup membership. Methods: Patients with cervical spondylotic radiculopathy undergoing ACDF are presented. Prognostic factors comprised demographic, health and surgery-related variables. Study outcomes were trajectories of neck disability index scores, numeric rating scales for neck/arm pain modeled with latent-class growth analysis. Associations were explored using robust Poisson models and reported with risk ratios and 95% confidence intervals. Results: Patients (N = 352; mean (SD) age = 50.9(9.5) years, 43.8% female) identified trajectories for disability (excellent=45.3%,fair=39.2%,poor=15.5%),arm pain (excellent=24.5%,good=52.0%,poor=23.5%),and neck pain (excellent=13.7%,good=63.1%,poor=23.2%). Greater physical and mental health-related quality of life were associated with a reduced risk of poor outcome(per SD,0.40[0.30,0.53]-0.80[0.65,0.99]), while higher risk for depression (per SD, 1.36[1.12,1.65]-2.26[1.84,2.78]), longer wait time(per 90 days, 1.31[1.05,1.63]-1.64[1.20,2.24]), and longer procedure time (per 30 min,1.07[1.03,1.10]-1.08[1.05,1.12]) were associated with an increased risk of poor outcome for all outcomes. Poor disability was increased with self-reported depression(3.03[1.76,5.21]), greater neck-to-arm pain ratio (2.63 [1.28 to 5.40]), ASA score > 2(2.26[1.33,3.83]), and preoperative opiates (2.05[1.18,3.56]), while preoperative physiotherapy (0.51[0.30, 0.88]), spinal injections (0.48[0.23 to 0.98]), and regular exercise (0.44 [0.24, 0.79]) decreased risk. Receiving compensation and smoking were associated with poor outcome for neck pain. Remaining candidate prognostic factors were not associated with clinical outcome. Conclusions: Perioperative factors were shown to decrease risk of poor outcomes for pain and disability two years following ACDF.
People living with dementia (PLWD) in residential aged care homes (RACHs) are frequently prescribed psychotropic medications due to the high prevalence of neuropsychiatric symptoms, also known as behaviors and psychological symptoms of dementia (BPSD). However, the gold standard to support BPSD is using psychosocial/non-pharmacological therapies.
Objective:
This study aims to describe and evaluate services and neuropsychiatric outcomes associated with the provision of psychosocial person-centered care interventions delivered by national multidisciplinary dementia-specific behavior support programs.
Methods:
A 2-year retrospective pre-post study with a single-arm analysis was conducted on BPSD referrals received from Australian RACHs to the two Dementia Support Australia (DSA) programs, the Dementia Behavior Management Advisory Service (DBMAS) and the Severe Behavior Response Teams (SBRT). Neuropsychiatric outcomes were measured using the Neuropsychiatric Inventory (NPI) total scores and total distress scores. The questionnaire version “NPI-Q” was administered for DBMAS referrals whereas the nursing home version “NPI-NH” was administered for SBRT referrals. Linear mixed effects models were used for analysis, with time, baseline score, age, sex, and case length as predictors. Clinical significance was measured using Cohen’s effect size (d; ≥0.3), the mean change score (MCS; 3 points for the NPI-Q and 4 points for the NPI-NH) and the mean percent change (MPC; ≥30%) in NPI parameters.
Results:
A total of 5,914 referrals (55.9% female, age 82.3 ± 8.6 y) from 1,996 RACHs were eligible for analysis. The most common types of dementia were Alzheimer’s disease (37.4%) and vascular dementia (11.7%). The average case length in DSA programs was 57.2 ± 26.3 days. The NPI scores were significantly reduced as a result of DSA programs, independent of covariates. There were significant reductions in total NPI scores as a result of the DBMAS (61.4%) and SBRT (74.3%) programs. For NPI distress scores, there were 66.5% and 69.1% reductions from baseline for the DBMAS and SBRT programs, respectively. All metrics (d, MCS, MPC) were above the threshold set for determining a clinically significant effect.
Conclusions:
Multimodal psychosocial interventions delivered by DSA programs are clinically effective as demonstrated by positive referral outcomes, such as improved BPSD and related caregiver distress.
We review 1982–1984 articles identifying Superfund sites in three nationalnewspapers. Articles almost never identify the race of nearby residents. Basedon sites receiving disproportionate coverage, readers might conclude thatSuperfund generally affected white, working-class families, but results do notsupport this narrative. In a pooled sample, neither race nor income predicts thenumber of times a site gets mentioned. When the sample is partitioned bynewspaper or by each newspaper's coverage of nearby sites, a positiverelationship emerges between the proportion of Hispanic or nonwhite residentsand the number of articles about a site. We discuss this apparentcontradiction.
Microscopic examination of blood smears remains the gold standard for laboratory inspection and diagnosis of malaria. Smear inspection is, however, time-consuming and dependent on trained microscopists with results varying in accuracy. We sought to develop an automated image analysis method to improve accuracy and standardization of smear inspection that retains capacity for expert confirmation and image archiving. Here, we present a machine learning method that achieves red blood cell (RBC) detection, differentiation between infected/uninfected cells, and parasite life stage categorization from unprocessed, heterogeneous smear images. Based on a pretrained Faster Region-Based Convolutional Neural Networks (R-CNN) model for RBC detection, our model performs accurately, with an average precision of 0.99 at an intersection-over-union threshold of 0.5. Application of a residual neural network-50 model to infected cells also performs accurately, with an area under the receiver operating characteristic curve of 0.98. Finally, combining our method with a regression model successfully recapitulates intraerythrocytic developmental cycle with accurate lifecycle stage categorization. Combined with a mobile-friendly web-based interface, called PlasmoCount, our method permits rapid navigation through and review of results for quality assurance. By standardizing assessment of Giemsa smears, our method markedly improves inspection reproducibility and presents a realistic route to both routine lab and future field-based automated malaria diagnosis.
Acute kidney injury leads to worse outcomes following paediatric cardiac surgery. There is a lack of literature focusing on acute kidney injury after the Hybrid stage 1 palliation for single ventricle physiology. Patients undergoing the Hybrid Stage 1, as a primary option, may have a lower incidence of kidney injury than previously reported. When present, kidney injury may increase the risk of post-operative morbidity and mortality.
Methods:
A retrospective, single centre review was conducted in patients with hypoplastic left heart syndrome who underwent Hybrid Stage 1 from 2008 to 2018. Acute kidney injury was defined as a dichotomous yes (meeting any injury criteria) or no (no injury) utilising two different criteria utilised in paediatrics. The impact of kidney injury on perioperative characteristics and 30-day mortality was analysed.
Results:
The incidence of acute kidney injury is 13.4–20.7%, with a severe injury rate of 2.4%. Patients without a prenatal diagnosis of hypoplastic left heart syndrome have a higher incidence of kidney injury than those prenatally diagnosed, (40% versus 14.5%, p = 0.024). Patients with acute kidney injury have a significantly higher incidence of 30-day mortality, 27.3%, compared to without, 5.6% (p = 0.047).
Discussion:
The incidence of severe acute kidney injury after the Hybrid Stage 1 palliation is low. A prenatal diagnosis may be associated with a lower incidence of kidney injury following the Hybrid Stage 1. Though uncommon, severe acute kidney injury following Hybrid Stage 1 may be associated with higher 30-day mortality.
A survey of Veterans’ Affairs Medical Centers on control of carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-producing CRE (CP-CRE) demonstrated that most facilities use VA guidelines but few screen for CRE/CP-CRE colonization regularly or regularly communicate CRE/CP-CRE status at patient transfer. Most respondents were knowledgeable about CRE guidelines but cited lack of adequate resources.
Generative neural networks (GNNs) have successfully used human-created designs to generate novel 3D models that combine concepts from disparate known solutions, which is an important aspect of design exploration. GNNs automatically learn a parameterization (or latent space) of a design space, as opposed to alternative methods that manually define a parameterization. However, GNNs are typically not evaluated using an explicit notion of physical performance, which is a critical capability needed for design. This work bridges this gap by proposing a method to extract a set of functional designs from the latent space of a point cloud generating GNN, without sacrificing the aforementioned aspects of a GNN that are appealing for design exploration. We introduce a sparsity preserving cost function and initialization strategy for a genetic algorithm (GA) to optimize over the latent space of a point cloud generating autoencoder GNN. We examine two test cases, an example of generating ellipsoid point clouds subject to a simple performance criterion and a more complex example of extracting 3D designs with a low coefficient of drag. Our experiments show that the modified GA results in a diverse set of functionally superior designs while maintaining similarity to human-generated designs in the training data set.
Although there is growing interest in mental health problems in university students there is limited understanding of the scope of need and determinants to inform intervention efforts.
Aims
To longitudinally examine the extent and persistence of mental health symptoms and the importance of psychosocial and lifestyle factors for student mental health and academic outcomes.
Method
Undergraduates at a Canadian university were invited to complete electronic surveys at entry and completion of their first year. The baseline survey measured important distal and proximal risk factors and the follow-up assessed mental health and well-being. Surveys were linked to academic grades. Multivariable models of risk factors and mental health and academic outcomes were fit and adjusted for confounders.
Results
In 1530 students surveyed at entry to university 28% and 33% screened positive for clinically significant depressive and anxiety symptoms respectively, which increased to 36% and 39% at the completion of first year. Over the academic year, 14% of students reported suicidal thoughts and 1.6% suicide attempts. Moreover, there was persistence and overlap in these mental health outcomes. Modifiable psychosocial and lifestyle factors at entry were associated with positive screens for mental health outcomes at completion of first year, while anxiety and depressive symptoms were associated with lower grades and university well-being.
Conclusions
Clinically significant mental health symptoms are common and persistent among first-year university students and have a negative impact on academic performance and well-being. A comprehensive mental health strategy that includes a whole university approach to prevention and targeted early-intervention measures and associated research is justified.
Craving in negative emotional situations (negative craving) is commonly associated with relapse and heavy alcohol use. Elevated dynorphin levels were associated with negative emotions, while variations in the OPRK1 and PDYN genes encoding OPRK1 receptor and dynorphins were associated with alcohol dependence.
Objectives
To investigate potential overlap in the genetic factors underlying, negative craving and alcohol dependence.
Aims
Examine the association of the negative craving and genetic variation in the OPRK1 and PDYN genes.
Methods
13 PDYN and 10 OPRK1 Single Nucleotide Polymorphisms (SNPs), including those previously reported to be associated with alcohol dependence were genotyped in 196 alcohol dependent subjects. The raw scores of the negative subscale of Inventory of Drug Taking Situations (IDTS) were utilized as a quantitative measure of negative craving. Logistic regression models were used to test for associations after controlling for age and gender.
Results
Gene-level haplotype testing demonstrated significant association of negative craving with variation in PDYN (p < 0.05) but not OPRK1 gene. The rs2281285 - rs199794 haplotype showed significant association (p = 0.0236) with negative craving, while rs2235749 - rs10485703 haplotype showed marginally significant association (p = 0.055). This replicates previous findings of association between these haplotypes and alcohol dependence. Negative craving was also associated with PDYN rs2281285 variant (p = 0.012) with estimated effect size of 6.95 (SE = 2.75). This new association finding was not significant after correction for multiple testing (p = 0.18).
Conclusions
Our findings support association of PDYN sequence variation with negative craving in alcohol dependent subjects. Future studies should investigate functional mechanisms of this association.
Lithium-treated patients with polyuria are at increased risk of lithium toxicity. We aimed to describe the clinical benefits and risks of different management strategies for polyuria in community lithium-treated patients.
Methods:
This is a naturalistic, observational, prospective 12-month cohort study of lithium-treated patients with polyuria attending a community mental health service in Dublin, Ireland. When polyuria was detected, management changed in one of four ways: (a) no pharmacological change; (b) lithium dose decrease; (c) lithium substitution; or (d) addition of amiloride.
Results:
Thirty-four participants were diagnosed with polyuria and completed prospective data over 12 months. Mean 24-hour urine volume decreased from 4852 to 4344 ml (p = 0.038). Mean early morning urine osmolality decreased from 343 to 338 mOsm/kg (p = 0.823). Mean 24-hour urine volume decreased with each type of intervention but did not attain statistical significance for any individual intervention group. Mean early morning urine osmolality decreased in participants with no pharmacological change and increased in participants who received a change in medication but these changes did not attain statistical significance. Only participants who discontinued lithium demonstrated potentially clinically significant changes in urine volume (mean decrease 747 ml in 24 hours) and early morning urine osmolality (mean increase 31 mOsm/kg) although this was not definitively proven, possibly owing to power issues.
Conclusions:
Managing polyuria by decreasing lithium dose does not appear to substantially improve objective measures of renal tubular dysfunction, whereas substituting lithium may do so. Studies with larger numbers and longer follow-up would clarify these relationships.
Disease surveillance in wildlife populations presents a logistical challenge, yet is critical in gaining a deeper understanding of the presence and impact of wildlife pathogens. Erinaceus coronavirus (EriCoV), a clade C Betacoronavirus, was first described in Western European hedgehogs (Erinaceus europaeus) in Germany. Here, our objective was to determine whether EriCoV is present, and if it is associated with disease, in Great Britain (GB). An EriCoV-specific BRYT-Green® real-time reverse transcription PCR assay was used to test 351 samples of faeces or distal large intestinal tract contents collected from casualty or dead hedgehogs from a wide area across GB. Viral RNA was detected in 10.8% (38) samples; however, the virus was not detected in any of the 61 samples tested from Scotland. The full genome sequence of the British EriCoV strain was determined using next generation sequencing; it shared 94% identity with a German EriCoV sequence. Multivariate statistical models using hedgehog case history data, faecal specimen descriptions and post-mortem examination findings found no significant associations indicative of disease associated with EriCoV in hedgehogs. These findings indicate that the Western European hedgehog is a reservoir host of EriCoV in the absence of apparent disease.
In Cameroon, there is a national programme engaged in the control of schistosomiasis and soil-transmitted helminthiasis. In certain locations, the programme is transitioning from morbidity control towards local interruption of parasite transmission. The volcanic crater lake villages of Barombi Mbo and Barombi Kotto are well-known transmission foci and are excellent context-specific locations to assess appropriate disease control interventions. Most recently they have served as exemplars of expanded access to deworming medications and increased environmental surveillance. In this paper, we review infection dynamics through time, beginning with data from 1953, and comment on the short- and long-term success of disease control. We show how intensification of local control is needed to push towards elimination and that further environmental surveillance, with targeted snail control, is needed to consolidate gains in preventive chemotherapy as well as empower local communities to take ownership of interventions.