Clinical prediction model to identify vulnerable patients in ambulatory surgery: towards optimal medical decision-making

__Background:__ Ambulatory surgery patients are at risk of adverse psychological outcomes such as anxiety, aggression, fatigue, and depression. We developed and validated a clinical prediction model to identify patients who were vulnerable to these psychological outcome parameters. __Methods:__ We prospectively assessed 383 mixed ambulatory surgery patients for psychological vulnerability, defined as the presence of anxiety (state/trait), aggression (state/trait), fatigue, and depression seven days after surgery. Three psychological vulnerability categories were considered–i.e., none, one, or multiple poor scores, defined as a score exceeding one standard deviation above the mean for each single outcome according to normative data. The following determinants were assessed preoperatively: sociodemographic (age, sex, level of education, employment status, marital status, having children, religion, nationality), medical (heart rate and body mass index), and psychological variables (self-esteem and self-efficacy), in addition to anxiety, aggression, fatigue, and depression. A prediction model was constructed using ordinal polytomous logistic regression analysis, and bootstrapping was applied for internal validation. The ordinal c-index (ORC) quantified the discriminative ability of the model, in addition to measures for overall model performance (Nagelkerke’s R2). __Results:__ In this population, 137 (36%) patients were identified as being psychologically vulnerable after surgery for at least one of the psychological outcomes. The most parsimonious and optimal prediction model combined sociodemographic variables (level of education, having children, and nationality) with psychological variables (trait anxiety, state/trait aggression, fatigue, and depression). Model performance was promising: R2 = 30% and ORC = 0.76 after correction for optimism. __Conclusion:__ This study identified a substantial group of vulnerable patients in ambulatory surgery. The proposed clinical prediction model could allow healthcare professionals the opportunity to identify vulnerable patients in ambulatory surgery, although additional modification and validation are needed. (ClinicalTrials.gov number, NCT01441843)

Commercially available industry-relevant software in the education of genome variant curation

BACKGROUND Genome analytics is a drastically expanding field, and there is an increasing demand for individuals with the necessary skillset to analyse the genome data that is being generated. A new Masters by coursework was developed to train individuals in genome analytics. Institutions analysing genomes commonly utilise in-house analysis tools, but increasingly commercial software packages that integrate AI are being considered in the research and diagnostic space (De La Vega et al., 2021). AIMS Evaluate the effectiveness of commercially available software as a tool for teaching variant analysis, classification and curation, enabling the analysis of real-world case examples for the teaching, training and assessment of students in the field of diagnostic genome analysis.   Assess students’ perspectives on work readiness after using commercially available tools in the educational environment. DESIGN AND METHODS Students were exposed to the use and limitations of a commercial software package for Human genome curation during two core units of the course. This software was used as part of both in-class training and in their assessment case studies. Students were invited to voluntarily complete an online survey including qualitative and quantitative components featuring Likert scale questions, both pre and post exposure to the software. Paired data from 23 individuals (73% response rate), most aged between 18 and 25, were recorded and anonymised prior to analysis. Qualitative data were thematically coded blind by two individuals independently using emergent coding (Charmaz, 2008). RESULTS AND CONCLUSIONS This project indicates that after the completion of the units that integrated commercially available industry software, we measured increased student confidence (increase in percentage reporting fairly confident or higher) in joining the genetic analysis workforce (significant change from 37% to 70%) and in completing job-specific tasks (significant increase in 7 out of 9 tasks of between 28% to 39%). The aspects of their studies the students valued in relation to these changes and their perception of the usefulness of integration of the commercial software were elucidated from qualitative theming, and can inform others looking to integrate commercially available software within their tertiary degree. REFERENCES Charmaz, K. (2008).  Grounded theory as an emergent method. In S. N. Hesse-Biber & P. Leavy (Eds.), Handbook of emergent methods. (pp. 155-170). The Guilford Press.  De La Vega, F.M., Chowdhury, S., Moore, B., Frise, E., McCarthy, J., Hernandez, E.J., Wong, T., James, K., Guidugli, L., Agrawal, P.B., Genetti, C.A., Brownstein, C.A., Beggs, A.H., Löscher, B.S., Franke, A., Boone, B., Levy, S.E., Õunap, K., Pajusalu, S., … Kingsmore, S.F. (2021). Artificial intelligence enables comprehensive genome interpretation and nomination of candidate diagnoses for rare genetic diseases. Genome Med, 13(1), 153. https://doi.org/10.1186/s13073-021-00965-

Factorization of Seiberg-Witten Curves and Compactification to Three Dimensions

We continue our study of nonperturbative superpotentials of four-dimensional N=2 supersymmetric gauge theories with gauge group U(N) on R^3 x S^1, broken to N=1 due to a classical superpotential. In a previous paper, hep-th/0304061, we discussed how the low-energy quantum superpotential can be obtained by substituting the Lax matrix of the underlying integrable system directly into the classical superpotential. In this paper we prove algebraically that this recipe yields the correct factorization of the Seiberg-Witten curves, which is an important check of the conjecture. We will also give an independent proof using the algebraic-geometrical interpretation of the underlying integrable system.Comment: laTeX, 14 pages, uses AMSmat

Intestinal Fatty Acid Binding Protein as a Predictor of Early Mesenteric Injury Preceding Clinical Presentation:A Case Report

Introduction: Diagnosing non-occlusive mesenteric ischaemia (NOMI) in patients is complicated, due to poor signs and symptoms and non-specific laboratory tests, leading to a high mortality rate. This case study presents the rare case of a patient who developed mesenteric ischaemia after an emergency thoracic endovascular aneurysm repair (TEVAR) for a type B aortic dissection (TBAD) and peri-operative cardiogenic shock. Study outcomes revealed that intestinal fatty acid binding protein (I-FABP) identified early mucosal damage two days before the clinical presentation. Report: A 43 year old male patient was admitted to the emergency department with an acute TBAD and a dissection of the superior mesenteric artery (SMA), for which TEVAR was performed with additional stent placement in the SMA. Peri-operatively, the patient went into cardiogenic shock with a sustained period of hypotension. Post-operatively, the plasma I-FABP levels were measured prospectively, revealing an initial increase on post-operative day five (551.1 pg/mL), which continued beyond day six (610.3 pg/mL). On post-operative day seven, the patient developed a fever and demonstrated signs of peritonitis and bowel perforation. He underwent an emergency laparotomy, followed by an ileocaecal resection (&lt;100 cm) with a transverse ileostomy. Pathological analysis confirmed the diagnosis of mesenteric ischaemia. Discussion: The diagnosis of NOMI in critically ill patients is often complicated, and the currently available diagnostic markers lack the specificity and sensitivity to detect early intestinal injury. This case report highlights that elevated I-FABP in plasma levels may indicate the presence of early mesenteric injury. Further research needs to be conducted before I-FABP can be applied in daily practice.</p

Nonperturbative Superpotentials and Compactification to Three Dimensions

We consider four-dimensional N=2 supersymmetric gauge theories with gauge group U(N) on R^3 x S^1, in the presence of a classical superpotential. The low-energy quantum superpotential is obtained by simply replacing the adjoint scalar superfield in the classical superpotential by the Lax matrix of the integrable system that underlies the 4d field theory. We verify in a number of examples that the vacuum structure obtained in this way matches precisely that in 4d, although the degrees of freedom that appear are quite distinct. Several features of 4d field theories, such as the possibility of lifting vacua from U(N) to U(tN), become particularly simple in this framework. It turns out that supersymmetric vacua give rise to a reduction of the integrable system which contains information about the field theory but also about the Dijkgraaf-Vafa matrix model. The relation between the matrix model and the quantum superpotential on R^3 x S^1 appears to involve a novel kind of mirror symmetry.Comment: LaTeX, 45 pages, uses AmsMath, minor correction, reference adde

Distribution and ecology of parent taxa of pollen lodged within the Latin American Pollen Database

The cornerstone of palaeoecological research, concerned with vegetation dynamics over the recent geological past, is a good understanding of the present-day ecology and distribution of the taxa. This is particularly necessary in areas of high floral diversity such as Latin America. Vegetation reconstructions, based on numerous pollen records, now exist with respect to all major vegetation associations from Latin America. With this ever-increasing number of sedimentary records becoming available, there is a need to collate this information and to provide information concerning ecology and distribution of the taxa concerned. The existing Latin American Pollen Database (LAPD) meets the first of these needs. Information concerning the ecology and distribution of the parent taxa responsible for producing the pollen, presently lodged within the LAPD, is the focus of this paper. The 'dictionary' describes the ecology and distribution of the parent taxa responsible for producing pollen identified within sedimentary records. These descriptions are based on a wide range of literature and extensive discussions with members of the palaeoecological community working in different parts of Latin America investigating a range of different vegetation types.Fil: Marchant, Robert. University of Amsterdam; Países BajosFil: Almeida, Lucía. Universidad Nacional Autónoma de México; MéxicoFil: Behling, Hermann. Center for Tropical Maritime Ecology; AlemaniaFil: Berrio, Juan Carlos. University of Amsterdam; Países BajosFil: Bush, Mark. West University Boulevard; Estados UnidosFil: Cleef, Antoine. University of Amsterdam; Países BajosFil: Duivenvoorden, Joost. University of Amsterdam; Países BajosFil: Kappelle, Maarten. Instituto Nacional de Biodiversidad (INBio); Costa RicaFil: De Oliveira, Paulo. Universidade de Sao Paulo; BrasilFil: de Oliveira, Ary Teixeira. Universidade Federal de Lavras; BrasilFil: Lozano García, Socorro. Universidad Nacional Autónoma de México; MéxicoFil: Hooghiemstra, Henry. University of Amsterdam; Países BajosFil: Ledru, Marie Pierre. Instituto de Geociencias; BrasilFil: Ludlow Wiechers, Beatriz. Universidad Nacional Autónoma de México; MéxicoFil: Markgraf, Vera. University of Colorado; Estados UnidosFil: Mancini, Maria Virginia. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Laboratorio de Paleoecología y Palinología; ArgentinaFil: Paez, Marta Mercedes. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Laboratorio de Paleoecología y Palinología; ArgentinaFil: Prieto, Aldo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Laboratorio de Paleoecología y Palinología; ArgentinaFil: Rangel, Olando. Universidad Nacional de Colombia; ColombiaFil: Salgado Labouriau, Maria Lea. Universidade do Brasília; Brasi

The quick motor function test: a new tool to rate clinical severity and motor function in Pompe patients

Pompe disease is a lysosomal storage disorder characterized by progressive muscle weakness. With the emergence of new treatment options, psychometrically robust outcome measures are needed to monitor patients’ clinical status. We constructed a motor function test that is easy and quick to use. The Quick Motor Function Test (QMFT) was constructed on the basis of the clinical expertise of several physicians involved in the care of Pompe patients; the Gross Motor Function Measure and the IPA/Erasmus MC Pompe survey. The test comprises 16 items. Validity and test reliability were determined in a cohort of 91 Pompe patients (5 to 76 years of age). In addition, responsiveness of the scale to changes in clinical condition over time was examined in a subgroup of 18 patients receiving treatment and 23 untreated patients. Interrater and intrarater reliabilities were good (intraclass correlation coefficients: 0.78 to 0.98 and 0.76 to 0.98). The test correlated strongly with proximal muscle strength assessed by hand held dynamometry and manual muscle testing (rs= 0.81, rs=0.89), and showed significant differences between patient groups with different disease severities. A clinical-empirical exploration to assess responsiveness showed promising results, albeit it should be repeated in a larger group of patients. In conclusion, the Quick Motor Function Test can reliably rate clinical severity and motor function in children and adults with Pompe disease

Anti-tumour activity of bisphosphonates in preclinical models of breast cancer

There is increasing evidence of anti-tumour effects of bisphosphonates from pre-clinical studies, supporting a role for these drugs beyond their traditional use in treatment of cancer-induced bone disease. A range of model systems have been used to investigate the effects of different bisphosphonates on tumour growth, both in bone and at peripheral sites. Most of these studies conclude that bisphosphonates cause a reduction in tumour burden, but that early intervention and the use of high and/or repeated dosing is required. Successful eradication of cancer may only be achievable by targeting the tumour cells directly whilst also modifying the tumour microenvironment. In line with this, bisphosphonates are demonstrated to be particularly effective at reducing breast tumour growth when used in combination with agents that directly target cancer cells. Recent studies have shown that the effects of bisphosphonates on breast tumours are not limited to bone, and that prolonged anti-tumour effects may be achieved following their inclusion in combination therapy. This has opened the field to a new strand of bisphosphonate research, focussed on elucidating their effects on cells and components of the local, regional and distal tumour microenvironment. This review highlights the recent developments in relation to proposed anti-tumour effects of bisphosphonates reported from in vitro and in vivo models, and summarises the data from key breast cancer studies. Evidence for effects on different processes and cell types involved in cancer development and progression is discussed, and the main outstanding issues identified

The Atacama Cosmology Telescope: A Measurement of the DR6 CMB Lensing Power Spectrum and its Implications for Structure Growth

We present new measurements of cosmic microwave background (CMB) lensing over $9400$ sq. deg. of the sky. These lensing measurements are derived from the Atacama Cosmology Telescope (ACT) Data Release 6 (DR6) CMB dataset, which consists of five seasons of ACT CMB temperature and polarization observations. We determine the amplitude of the CMB lensing power spectrum at $2.3\%$ precision ($43\sigma$ significance) using a novel pipeline that minimizes sensitivity to foregrounds and to noise properties. To ensure our results are robust, we analyze an extensive set of null tests, consistency tests, and systematic error estimates and employ a blinded analysis framework. The baseline spectrum is well fit by a lensing amplitude of $A_{\mathrm{lens}}=1.013\pm0.023$ relative to the Planck 2018 CMB power spectra best-fit $\Lambda$CDM model and $A_{\mathrm{lens}}=1.005\pm0.023$ relative to the $\text{ACT DR4} + \text{WMAP}$ best-fit model. From our lensing power spectrum measurement, we derive constraints on the parameter combination $S^{\mathrm{CMBL}}_8 \equiv \sigma_8 \left({\Omega_m}/{0.3}\right)^{0.25}$ of $S^{\mathrm{CMBL}}_8= 0.818\pm0.022$ from ACT DR6 CMB lensing alone and $S^{\mathrm{CMBL}}_8= 0.813\pm0.018$ when combining ACT DR6 and Planck NPIPE CMB lensing power spectra. These results are in excellent agreement with $\Lambda$CDM model constraints from Planck or $\text{ACT DR4} + \text{WMAP}$ CMB power spectrum measurements. Our lensing measurements from redshifts $z\sim0.5$--$5$ are thus fully consistent with $\Lambda$CDM structure growth predictions based on CMB anisotropies probing primarily $z\sim1100$. We find no evidence for a suppression of the amplitude of cosmic structure at low redshiftsComment: 45+21 pages, 50 figures. Prepared for submission to ApJ. Also see companion papers Madhavacheril et al and MacCrann et a

The Atacama Cosmology Telescope: High-resolution component-separated maps across one-third of the sky

Observations of the millimeter sky contain valuable information on a number of signals, including the blackbody cosmic microwave background (CMB), Galactic emissions, and the Compton-$y$ distortion due to the thermal Sunyaev-Zel'dovich (tSZ) effect. Extracting new insight into cosmological and astrophysical questions often requires combining multi-wavelength observations to spectrally isolate one component. In this work, we present a new arcminute-resolution Compton-$y$ map, which traces out the line-of-sight-integrated electron pressure, as well as maps of the CMB in intensity and E-mode polarization, across a third of the sky (around 13,000 sq.~deg.). We produce these through a joint analysis of data from the Atacama Cosmology Telescope (ACT) Data Release 4 and 6 at frequencies of roughly 93, 148, and 225 GHz, together with data from the \textit{Planck} satellite at frequencies between 30 GHz and 545 GHz. We present detailed verification of an internal linear combination pipeline implemented in a needlet frame that allows us to efficiently suppress Galactic contamination and account for spatial variations in the ACT instrument noise. These maps provide a significant advance, in noise levels and resolution, over the existing \textit{Planck} component-separated maps and will enable a host of science goals including studies of cluster and galaxy astrophysics, inferences of the cosmic velocity field, primordial non-Gaussianity searches, and gravitational lensing reconstruction of the CMB.Comment: The Compton-y map and associated products will be made publicly available upon publication of the paper. The CMB T and E mode maps will be made available when the DR6 maps are made publi