Deconstruction of compound objects from image sets

We propose a method to recover the structure of a compound object from multiple silhouettes. Structure is expressed as a collection of 3D primitives chosen from a pre-defined library, each with an associated pose. This has several advantages over a volume or mesh representation both for estimation and the utility of the recovered model. The main challenge in recovering such a model is the combinatorial number of possible arrangements of parts. We address this issue by exploiting the sparse nature of the problem, and show that our method scales to objects constructed from large libraries of parts

One pot ‘click’ reactions: tandem enantioselective biocatalytic epoxide ring opening and [3+2] azide alkyne cycloaddition

Halohydrin dehalogenase (HheC) can perform enantioselective azidolysis of aromatic epoxides to 1,2-azido alcohols which are subsequently ligated to alkynes producing chiral hydroxy triazoles in a one-pot procedure with excellent enantiomeric excess.

Response article to commentary on our article titled ‘Volvulus of the gastrointestinal tract’

Peer reviewe

The dual continua in youth mental health policy and practice : screening and intervention for low mental wellbeing in youth to achieve targeted prevention

Background: The mental health of young people in Australia and other nations has declined dramatically over the last decade and a half. While an increase in youth mental healthcare services is needed to meet rising demand, on its own, this is unlikely to reverse the concerning trend. A greater focus on prevention is needed. Aims: This article aims to propose an innovative, theoretically-grounded approach to prevention that complements more common population-based (i.e., changing risk and protective factors) and targeted (i.e., supporting individuals with subthreshold symptoms of mental illness) approaches. Aligned with the dual-continua model of mental health (i.e., where mental well-being and ill-health are distinct dimensions of overall mental health), this third approach focuses on addressing low levels of mental wellbeing, which is both a significant predictor of future mental ill-health and a distressing and disabling state that requires intervention in its own right. Recommendations: Large-scale screening for low mental wellbeing, using psychometrically sound tools, could be conducted online and through schools, higher education, and primary care services. Those with low mental wellbeing could be linked to community services offering evidence-based interventions. This approach is likely to carry less stigma and may be easier to achieve than targeting those with subthreshold symptoms through clinical services. Conclusions: The dire state of youth mental health is an urgent call-to-action to adopt novel approaches to address this crisis. We need to make better use of the available evidence and tools at-hand to strengthen our focus on low mental wellbeing, not just mental ill-health. © 2025 Elsevier Gmb

Evaluating the Safety of Performing Flexible Cystoscopy When Urinalysis Suggests Presence of “Infection”:Results of a Prospective Clinical Study in 2350 patients

BACKGROUND: There is significant underutilisation of allocated health service resources when a scheduled flexible cystoscopy (FC) is cancelled because a pre-cystoscopy urinalysis (PCU) suggests “infection”, despite patients being asymptomatic for urinary tract infection (UTI). OBJECTIVE: To evaluate the risk of UTI or urinary sepsis when FC is performed in asymptomatic patients with a PCU positive for leucocyte esterase and/or nitrites. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study was conducted in a high-volume UK centre recruiting all patients undergoing outpatient FC. INTERVENTION: A protocol was developed to guide response to PCU performed prior to FC, which was performed regardless of the result, unless patients were symptomatic for UTI. All patients completed a questionnaire to identify risk factors and were followed up via a telephone survey and a review of electronic clinical records. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Post-FC UTI was defined as hospital admission with UTI/urinary sepsis or if patients were symptomatic for UTI with receipt of antibiotics or with positive urine culture and sensitivity. An analysis of the association was performed. RESULTS AND LIMITATIONS: An initial pilot study confirmed the safety and feasibility of our protocol. Of 1996 patients, 136 (6.8%) developed a UTI by our definition, with 51 (2.6%) having a culture-proven infection. The risk was higher in patients with a positive PCU (odds ratio [OR] 1.61, 95% confidence interval [CI] = 1.07–2.40, p = 0.02), history of UTI (OR 1.72, 95% CI = 1.09–2.73, p = 0.02), or a bladder tumour on FC (OR 2.22, 95% CI = 1.27–3.90, p = 0.005). No patient with a positive PCU developed urinary sepsis. The main limitation of this study was the lack of pre-protocol control. CONCLUSIONS: We observed a clinically low and acceptable risk of UTI, with no incidence of sepsis, when FC was performed in asymptomatic patients with a PCU suggesting “infection”. Routine cancellation of these patients is unnecessary and may worsen the burden on health service resources. PATIENT SUMMARY: We evaluated the safety of performing flexible cystoscopy when the urine dipstick on the day suggested presence of an “infection” but the patient had no symptoms of urinary tract infection (UTI). Our study in over 2000 patients demonstrated a low incidence of UTI, and none of these patients developed sepsis. We therefore recommend that flexible cystoscopy should not be cancelled automatically on the basis of the dipstick result alone, as it might delay a time-sensitive crucial diagnosis

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Association between polygenic risk for Major Depression and brain structure in a mega-analysis of 50,975 participants across 11 studies

Major Depression (MD) is a prevalent, disabling and life-limiting condition. The neurobiological associations of genetic risk for MD remain under-explored in large samples, with no comprehensive mega-analysis conducted to date. Our study analysed data from 11 separate studies, encompassing 50,975 participants from the ENIGMA Major Depressive Disorder Working Group. We developed highly consistent genetic and neuroimaging protocols and applied these throughout all participating studies, together with rigorous genetic methods to remove overlap between the polygenic risk scores (PRS) training and testing samples. Elevated PRS for MD correlated with lower intracranial volume and lower global measure of cortical surface area (β ICV = −0.017, p ICV = 1.97 × 10 −6; β Surf = −0.013, p Surf = 4.5 × 10 −4; pFDR &lt; 3.62 × 10 −4). The most significant cortical association was observed in the surface area of the frontal lobe (β = −0.011, p = 2.85 × 10 −6, pFDR = 1.42 × 10 −5), particularly in the left medial orbito-frontal gyrus (β = −0.021, p = 9.48 × 10 −8, pFDR = 1.25 × 10 −5). In subcortical regions, lower volumes of the thalamus, hippocampus, and pallidum correlated with higher PRS of MD (β ranged from −0.011 to −0.015, p ranged from 0.002–1.73 × 10 −5, pFDR &lt; 0.006). In a subsample of young individuals only (&lt;25 years old, N = 5570), although there were no FDR-significant findings, directions of effects were highly consistent between the analyses of cortical surface areas in youth and the full sample (71.2% in the same direction, exact binomial test p-value = 7.56 × 10 −4). Subsequent Mendelian randomisation analysis revealed potentially causal effects of smaller left hippocampal volume on higher liability for MD (Inverse variance weighted analysis β = −0.064, p = 8.04 × 10 −3, pFDR = 0.04). Our findings represent an example of how extensive international collaborations can significantly advance our neurogenetic understanding of MD and give insights to avenues for early interventions in those at high risk for developing MD.</p