Risk factors for complications after emergency surgery for paediatric appendicitis: a national prospective observational cohort study.

Appendicectomy is a common procedure in children with a low risk of mortality, however, complication rates and risk factors are largely unknown. This study aimed to characterise the incidence and epidemiology of postoperative complications in children undergoing appendicectomy in the UK. This multicentre prospective observational cohort study, which included children aged 1-16 y who underwent surgery for suspected appendicitis, was conducted between November 2019 and January 2022. The primary outcome was 30-day postoperative morbidity. Data collected included: patient characteristics; comorbidities; and physiological status. Multivariable regression analysis was used to identify independent risk factors for poor outcomes. Data from 2799 children recruited from 80 hospitals were analysed, of which 185 (7%) developed postoperative complications. Children from black and 'other' minority ethnic groups were at significantly higher risk of poor outcomes: OR (95%CI) 4.13 (1.87-9.08), p < 0.001 and 2.08 (1.12-3.87), p = 0.021, respectively. This finding was independent of socio-economic status and type of appendicitis found on histology. Other risk factors for complications included: ASA physical status ≥ 3 (OR (95%CI) 4.05 (1.70-9.67), p = 0.002); raised C-reactive protein (OR 95%CI 1.01 (1.00-1.01), p < 0.001); pyrexia (OR (95%CI) 1.77(1.20-2.63), p = 0.004); and peri-operative oxygen supplementation (OR (95%CI) 4.20 (1.44-12.24), p = 0.009). In the UK NHS, which is a universally accessible healthcare system, ethnicity, but not socio-economic status, was associated with an increased risk of postoperative complications in children having surgery for acute appendicitis. Further evaluations and interventions are required to address this health inequality in keeping with NHS and international priorities.

Patient interest in and clinician reservations on polygenic embryo screening: a qualitative study of stakeholder perspectives.

PURPOSE: We explored and compared perspectives of reproductive endocrinology and infertility specialists (REIs) and in vitro fertilization (IVF) patients regarding polygenic embryo screening (PES), a new type of preimplantation screening that estimates the genetic chances of developing polygenic conditions and traits in the future. METHODS: Qualitative thematic analysis of semi-structured interviews with US-based REIs and IVF patients. RESULTS: Clinicians and patients often held favorable views of screening embryos for physical or psychiatric conditions, though clinicians tended to temper their positive attitudes with specific caveats. Clinicians also expressed negative views about screening embryos for traits more frequently than patients, who generally held more positive views. Most clinicians were either unwilling to discuss or offer PES to patients or were willing to do so only under certain circumstances, while many patients expressed interest in PES. Both stakeholder groups envisioned multiple potential benefits or uses of PES and raised multiple potential, interrelated concerns about PES. CONCLUSION: A gap exists between clinician and patient attitudes toward PES; clinicians generally maintained reservations about such screening and patients indicated interest in it. Clinicians and patients sometimes imagined using PES to prepare for the birth of a predisposed or "affected" individual-a rationale that is often associated with prenatal testing. Many clinicians and patients held different attitudes depending on what is specifically screened, despite the sometimes blurry distinction between conditions and traits. Considerations raised by clinicians and patients may help guide professional societies in developing guidelines to navigate the uncertain terrain of PES.

Transversal optical singularity induced precision measurement of step-nanostructures.

Optical singularities indicate zero-intensity points in space where parameters, such as phase, polarization, are undetermined. Vortex beams such as the Laguerre-Gaussian modes are characterized by a phase factor eilθ, and contain a phase singularity in the middle of its beam. In the case of a transversal optical singularity (TOS), it occurs perpendicular to the propagation, and its phase integral is 2π in nature. Since it emerges within a nano-size range, one expects that TOSs could be sensitive in the light-matter interaction process and could provide a great possibility for accurate determination of certain parameters of nanostructure. Here, we propose to use TOSs generated by a three-wave interference to illuminate a step nanostructure. After interaction with the nanostructure, the TOS is scattered into the far field. The scattering direction can have a relation with the physical parameters of the nanostructure. We show that by monitoring the spatial coordinates of the scattered TOS, its propagation direction can be determined, and as consequence, certain physical parameters of the step nanostructure can be retrieved with high precision.

Is cardiorespiratory fitness associated with cognitive outcomes in mid-adulthood? Findings from the 1958 British birth cohort.

Identifying causal factors to intervene on to delay age-related declines in cognitive function is urgently needed. We examined associations between non-exercise testing cardiorespiratory fitness (NETCRF; estimated using sex, age, body mass index, resting heart rate, and physical activity) at 45 years and cognitive function outcomes (immediate and delayed verbal memory; verbal fluency; visual processing speed) at 50 years in 8130 participants from the 1958 British birth cohort. In unadjusted models, higher NETCRF was associated with better cognitive function across all outcomes. When adjusted for confounding factors, associations disappeared. In this cohort, associations between 45 years NETCRF and 50 years cognitive function likely result from confounding factors.

Associations between diabetes status and grip strength trajectory sub-groups in adulthood: findings from over 16 years of follow-up in the MRC National Survey of Health and Development.

BACKGROUND: Cross-sectional studies suggest a relationship between diabetes status and weaker grip strength (GS) in adulthood and limited evidence from longitudinal studies has focussed on the association with average change in GS. We aimed to investigate whether diabetes status was related to membership of distinct GS trajectories in mid-to-late adulthood in 2,263 participants in the Medical Research Council National Survey of Health and Development. METHODS: Grip strength (kg) was measured at 53, 60-64 and 69 years. Pre-/diabetes was defined at 53 years based on HbA1c > 5.6% and/or doctor-diagnosis of diabetes. Sex-specific latent class trajectory models were developed and multinomial logistic regression was used to investigate the association between pre-/diabetes status and membership into GS trajectory classes. RESULTS: For both males and females, a 3-class solution ('High', 'Intermediate', 'Low') provided the best representation of the GS data and the most plausible solution. There was no evidence that pre-/diabetes status was associated with class membership in either sex: e.g., adjusted odds ratios of being in the 'Low' class (vs. 'High') for males with pre-/diabetes (vs. no-diabetes) was 1.07 (95% CI:0.45,2.55). CONCLUSION: Using a flexible data-driven approach to identify GS trajectories between 53 and 69 years, we observed three distinct GS trajectories, all declining, in both sexes. There was no association between pre-/diabetes status at 53 years and membership into these GS trajectories. Understanding the diabetes status-GS trajectories association is vital to ascertain the consequences that projected increases in pre-/diabetes prevalence's are likely to have.

Risk factors for fixation failure in intertrochanteric fractures treated with cephalomedullary nailing: a retrospective study of 251 patients.

This study aimed to identify the variables associated with fixation failure in intertrochanteric fractures treated with cephalomedullary nailing (CMN). We retrospectively analyzed 251 consecutive patients who underwent surgery between January 2016 and July 2019. In order to identify predictors of failure (cut-out, cut-through, and/or nonunion), we analyzed: gender, age, fracture stability (according to the AO/OTA Classification), femoral neck angle (FNA), FNA as compared to the contralateral hip, lag screw position, and tip-apex distance (TAD). The failure rate was 9.6%: there were 10 cut-outs (4%), 7 non-unions (2.8%), and 7 cut-throughs (2.8%). Univariate logistic regression analysis showed that the risk factors for fixation failure were: female sex (p= 0.018), FNA <125° (p= 0.003), a difference in FNA of 7.5° as compared to the contralateral hip on the lateral radiograph (p= <0.0001), superior (p= 0.0141) and anterior position (p= <0.0001) of the lag screw, and TAD >25mm (p= 0.016). According to the multivariate analysis, female gender (OR 12.92 ; p 0.0019), the difference in FNA on the lateral view (OR 1.36; p < 0.001), and the anterior position of the screw in the femoral head (OR14.01;p <0.001) were confirmed as independent predictors of failure. In order to avoid failures in intertrochanteric hip fractures treated with CMN, this study confirmed the importance of achieving an accurate reduction on the lateral plane and avoiding the anterior position of the screw on the femoral head.

Optical singularity assisted method for accurate parameter detection of step-shaped nanostructure in coherent Fourier scatterometry.

Accurate determination of the physical parameters of nanostructures from optical far-field scattering is an important and challenging topic in the semiconductor industry. Here, we propose a novel metrology method to determine simultaneously the height and side-wall angle of a step-shaped silicon nanostructure. By employing an optical singular beam into a typical coherent Fourier scatterometry system, both parameters can be retrieved through analyzing the intensity profile of the far-field scattering pattern. The use of singular beam is shown to be sensitive to slight changes of the parameters of the step. By changing the relative direction between the singularity and structure, the height and side-wall angle can both be retrieved with high precision. This new method is robust, simple, and can provide valuable means for micro-and-nano- metrologies.

Direct detection of polystyrene equivalent nanoparticles with diameter of 21 nm (∼λ/19) using coherent Fourier scatterometry: erratum.

We present an erratum to our article Kolenov, D., et al. "Direct detection of polystyrene equivalent nanoparticles with a diameter of 21 nm ( ∼ λ/19) using coherent Fourier scatterometry." Opt. Express29, 16487 (2021)10.1364/OE.421145.

Polygenic embryo screening: four clinical considerations warrant further attention.

Recent advances in developing polygenic scores have made it possible to screen embryos for common, complex conditions and traits. Polygenic embryo screening (PES) is currently offered commercially, and though there has been much recent media and academic coverage, reproductive specialists' points of view have not yet been prominent in these discussions. We convened a roundtable of multidisciplinary experts, including reproductive specialists to discuss PES and its implications. In this Opinion, we describe four clinically relevant issues associated with the use of PES that have not yet been discussed in the literature and warrant consideration.

Obesity in early adulthood and physical functioning in mid-life: Investigating the mediating role of c-reactive protein.

INTRODUCTION: Obesity in adulthood is associated with reduced physical functioning (PF) at older ages. However, mechanisms underpinning this association are not well understood. We investigated whether and the extent to which C-reactive protein (CRP) mediates the association between early-adult obesity and mid-life PF. METHODS: We used data from 8495 participants in the 1958 British birth cohort study. Body mass index (BMI), CRP and PF were measured at 33, 45 and 50y, respectively. Poor PF was defined as the lowest (sex-specific) 10% on the Short-form 36 Physical Functioning subscale. We accounted for prospectively measured confounders in early-life (e.g., social class at birth) and in mid-adulthood (e.g., 42y comorbidities). We decomposed the total effect of early-adult obesity on mid-life PF into direct and indirect (via CRP) effects, by employing a mediation analysis based on parametric g-computation. RESULTS: The estimated total effect of obesity at 33y on poor PF at 50y, expressed as an odds ratio (OR), was 2.41 (95% CI: 1.89, 3.08). The direct effect of obesity on poor PF (i.e., not operating via CRP), was 1.97 (95% CI: 1.51, 2.56), with an indirect effect of 1.23 (95% CI: 1.10, 1.37). As such, the proportion of the total effect which was mediated by the effect of obesity on CRP at 45y, was 23.27% (95% CI: 8.64%, 37.90%). CONCLUSION: Obesity in early-adulthood was associated with over twice the odds of poor PF in mid-life, with approximately 23% of the obesity effect operating via a downstream effect on CRP. As current younger generations are likely to spend greater proportions of their life course in older age and with obesity, both of which are associated with poor PF, there is an urgent need to identify mechanisms, and thus potential modifiable intermediaries, linking obesity to poor PF.

Capturing the non-stationarity of whole-brain dynamics underlying human brain states.

Brain dynamics depicts an extremely complex energy landscape that changes over time, and its characterisation is a central unsolved problem in neuroscience. We approximate the non-stationary landscape sustained by the human brain through a novel mathematical formalism that allows us characterise the attractor structure, i.e. the stationary points and their connections. Due to its time-varying nature, the structure of the global attractor and the corresponding number of energy levels changes over time. We apply this formalism to distinguish quantitatively between the different human brain states of wakefulness and different stages of sleep, as a step towards future clinical applications.

Direct detection of polystyrene equivalent nanoparticles with a diameter of 21 nm (∼λ/19) using coherent Fourier scatterometry.

Coherent Fourier scatterometry (CFS) has been introduced to fulfil the need for noninvasive and sensitive inspection of subwavelength nanoparticles in the far field. The technique is based on detecting the scattering of coherent light when it is focused on isolated nanoparticles. In the present work, we describe the results of an experimental study aimed at establishing the actual detection limits of the technique, namely the smallest particle that could be detected with our system. The assessment for particles with a diameter smaller than 40 nm is carried out using calibrated nano-pillars of photoresist on silicon wafers that have been fabricated with e-beam lithography. We demonstrate the detection of polystyrene equivalent nanoparticles of diameter of 21 nm with a signal-to-noise ratio of 4 dB using the illuminating wavelength of 405 nm.

Trends in the molecular epidemiology and population genetics of emerging Sporothrix species.

Sporothrix (Ophiostomatales) comprises species that are pathogenic to humans and other mammals as well as environmental fungi. Developments in molecular phylogeny have changed our perceptions about the epidemiology, host-association, and virulence of Sporothrix. The classical agent of sporotrichosis, Sporothrix schenckii, now comprises several species nested in a clinical clade with S. brasiliensis, S. globosa, and S. luriei. To gain a more precise view of outbreaks dynamics, structure, and origin of genetic variation within and among populations of Sporothrix, we applied three sets of discriminatory AFLP markers (#3 EcoRI-GA/MseI-TT, #5 EcoRI-GA/MseI-AG, and #6 EcoRI-TA/MseI-AA) and mating-type analysis to a large collection of human, animal and environmental isolates spanning the major endemic areas. A total of 451 polymorphic loci were amplified in vitro from 188 samples, and revealed high polymorphism information content (PIC = 0.1765-0.2253), marker index (MI = 0.0001-0.0002), effective multiplex ratio (E = 15.1720-23.5591), resolving power (Rp = 26.1075-40.2795), discriminating power (D = 0.9766-0.9879), expected heterozygosity (H = 0.1957-0.2588), and mean heterozygosity (Havp  = 0.000007-0.000009), demonstrating the effectiveness of AFLP markers to speciate Sporothrix. Analysis using the program structure indicated three genetic clusters matching S. brasiliensis (population 1), S. schenckii (population 2), and S. globosa (population 3), with the presence of patterns of admixture amongst all populations. AMOVA revealed highly structured clusters (PhiPT = 0.458-0.484, P < 0.0001), with roughly equivalent genetic variability within (46-48 %) and between (52-54 %) populations. Heterothallism was the exclusive mating strategy, and the distributions of MAT1-1 or MAT1-2 idiomorphs were not significantly skewed (1:1 ratio) for S. schenckii (χ2 = 2.522; P = 0.1122), supporting random mating. In contrast, skewed distributions were found for S. globosa (χ2 = 9.529; P = 0.0020) with a predominance of MAT1-1 isolates, and regional differences were highlighted for S. brasiliensis with the overwhelming occurrence of MAT1-2 in Rio de Janeiro (χ2 = 14.222; P = 0.0002) and Pernambuco (χ2 = 7.364; P = 0.0067), in comparison to a higher prevalence of MAT1-1 in the Rio Grande do Sul (χ2 = 7.364; P = 0.0067). Epidemiological trends reveal the geographic expansion of cat-transmitted sporotrichosis due to S. brasiliensis via founder effect. These data support Rio de Janeiro as the centre of origin that has led to the spread of this disease to other regions in Brazil. Our ability to reconstruct the source, spread, and evolution of the ongoing outbreaks from molecular data provides high-quality information for decision-making aimed at mitigating the progression of the disease. Other uses include surveillance, rapid diagnosis, case connectivity, and guiding access to appropriate antifungal treatment.

Machine learning techniques applied for the detection of nanoparticles on surfaces using coherent Fourier scatterometry.

We present an efficient machine learning framework for detection and classification of nanoparticles on surfaces that are detected in the far-field with coherent Fourier scatterometry (CFS). We study silicon wafers contaminated with spherical polystyrene (PSL) nanoparticles (with diameters down to λ/8). Starting from the raw data, the proposed framework does the pre-processing and particle search. Further, the unsupervised clustering algorithms, such as K-means and DBSCAN, are customized to be used to define the groups of signals that are attributed to a single scatterer. Finally, the particle count versus particle size histogram is generated. The challenging cases of the high density of scatterers, noise and drift in the dataset are treated. We take advantage of the prior information on the size of the scatterers to minimize the false-detections and as a consequence, provide higher discrimination ability and more accurate particle counting. Numerical and real experiments are conducted to demonstrate the performance of the proposed search and cluster-assessment techniques. Our results illustrate that the proposed algorithm can detect surface contaminants correctly and effectively.

Superresolution effect due to a thin dielectric slab for imaging with radially polarized light.

Improving the image quality of small particles is a classic problem and especially challenging when the distance between particles are below the optical diffraction limit. We propose a imaging system illuminated with radially polarized light combined with a suitable substrate that contains a thin dielectric layer to demonstrate that the imaging quality can be enhanced. The coupling between the evanescent wave produced in a designed thin dielectric layer, the small particles and the propagating wave forms a mechanism to transfer sub-wavelength information about the particles to the far field. The smallest distinguished distance reaches to 0.634λ, when the imaging system is composed of a high numerical aperture (NA=0.9) lens and the illumination wavelength λ = 632nm, beyond the diffraction limit 0.678λ. The lateral resolution can be further improved by combining the proposed structure with superresolution microscopy techniques.

Epigenomic alterations define lethal CIMP-positive ependymomas of infancy.

Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.

Convolutional neural network applied for nanoparticle classification using coherent scatterometry data.

The analysis of 2D scattering maps generated in scatterometry experiments for detection and classification of nanoparticles on surfaces is a cumbersome and slow process. Recently, deep learning techniques have been adopted to avoid manual feature extraction and classification in many research and application areas, including optics. In the present work, we collected experimental datasets of nanoparticles deposited on wafers for four different classes of polystyrene particles (with diameters of 40, 50, 60, and 80 nm) plus a background (no particles) class. We trained a convolutional neural network, including its architecture optimization, and achieved 95% accurate results. We compared the performance of this network to an existing method based on line-by-line search and thresholding, demonstrating up to a twofold enhanced performance in particle classification. The network is extended by a supervisor layer that can reject up to 80% of the fooling images at the cost of rejecting only 10% of original data. The developed Python and PyTorch codes, as well as dataset, are available online.

Identification of Cystic Lesions by Secondary Screening of Familial Pancreatic Cancer (FPC) Kindreds Is Not Associated with the Stratified Risk of Cancer.

OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) are associated with risk of pancreatic ductal adenocarcinoma (PDAC). It is unclear if an IPMN in individuals at high risk of PDAC should be considered as a positive screening result or as an incidental finding. Stratified familial pancreatic cancer (FPC) populations were used to determine if IPMN risk is linked to familial risk of PDAC. METHODS: This is a cohort study of 321 individuals from 258 kindreds suspected of being FPC and undergoing secondary screening for PDAC through the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC). Computerised tomography, endoscopic ultrasound of the pancreas and magnetic resonance imaging were used. The risk of being a carrier of a dominant mutation predisposing to pancreatic cancer was stratified into three even categories (low, medium and high) based on: Mendelian probability, the number of PDAC cases and the number of people at risk in a kindred. RESULTS: There was a median (interquartile range (IQR)) follow-up of 2 (0-5) years and a median (IQR) number of investigations per participant of 4 (2-6). One PDAC, two low-grade neuroendocrine tumours and 41 cystic lesions were identified, including 23 IPMN (22 branch-duct (BD)). The PDAC case occurred in the top 10% of risk, and the BD-IPMN cases were evenly distributed amongst risk categories: low (6/107), medium (10/107) and high (6/107) (P = 0.63). CONCLUSIONS: The risk of finding BD-IPMN was independent of genetic predisposition and so they should be managed according to guidelines for incidental finding of IPMN.

An approach to the implementation of Low Impact Development measures towards an EcoCampus classification.

Impervious cover has important hydrologic impacts, namely the increased runoff volume and peak discharges in the rainwater network, which can lead to significant consequences like rapid urban floods with social, environmental and economic implications. LID (Low Impact Development) consist of distributed runoff management measures, like green roofs, pervious pavements, waterways covered with vegetation and filter trails, among others, that seek to control stormwater in the origin, reducing imperviousness. These solutions avoid increased runoff rate and volume, increase infiltration and groundwater recharge. The main goal of the research work here presented is to study the hydrological impact of LID's in UTAD (University of Trás-os-Montes e Alto Douro) campus, which is an institution focused on sustainability, since it has defined in its Strategic Plan to achieve, in a near future, an EcoCampus classification. To achieve the proposed goal, the campus area was studied in detail in order to evaluate the technical possibility of LID's implementation. A peak discharge comparison was made between the current situation and the one with LID's implementation, using the rational method. The results showed that peak discharges reduction between 68 and 95% may be achieved with LID solutions in UTAD campus.