A 3D mathematical model for planning ostectomy on long-bone angular deformities

This study describes a 3D mathematical model for planning a corrective ostectomy on long bones with angular deformities based on CT imaging. The use of three-dimensional information allows the model to compute and correct the bone angulation and rotation. The cutting point selection is developed minimizing the bone length reduction inherent in an ostectomy process. An example of its application on a two year old dog is shown at the end of the paper.Veterinari

Evaluation of a New, Rapid, Fully Automated Assay for the Measurement of ADAMTS13 Activity

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy (TMA) characterized by the severe deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity (< 10%). Rapid ADAMTS13 testing is crucial for an early diagnosis and optimal management of acute TTP. We evaluated the performance of the HemosIL AcuStar ADAMTS13 activity assay (Instrumentation Laboratory, Bedford, Massachusetts, United States), a fully automated chemiluminescent immunoassay with an analytical time of 33 minutes. A method comparison study was performed on 176 samples from 49 healthy donors and 127 TMA patients (109 TTP, 7 atypical hemolytic uremic syndrome, 11 other TMAs), comparing this new assay with an in-house FRETS-VWF73 assay and a commercial enzyme-linked immunosorbent assay (ELISA) (TECHNOZYM ADAMTS-13 Activity, Technoclone GmbH, Vienna, Austria). Agreement between methods was assessed with focus on ADAMTS13 activity less than 10%, the medical decision level relevant for TTP diagnosis. The HemosIL AcuStar ADAMTS13 Activity showed good correlation with both the FRETS-VWF73 (r = 0.96) and ELISA (r = 0.96) methods. Slope of the Passing-Bablok regression was 1.05 for FRETS-VWF73 and 1.02 for ELISA, and absolute bias at the medical decision level was +0.1 and +0.3%, respectively. The study also revealed high agreement with FRETS-VWF73 (kappa 0.97) and ELISA (kappa 0.98) methods in classifying TTP patients with a severe deficiency of ADAMTS13 activity. Because of its short turnaround time and full automation, the HemosIL AcuStar ADAMTS13 activity assay might become the assay of choice to rapidly test ADAMTS13 activity in plasma and thus establish the diagnosis of acute TTP in emergency settings

Composite Higgs Sketch

The coupling of a composite Higgs to the standard model fields can deviate substantially from the standard model values. In this case perturbative unitarity might break down before the scale of compositeness is reached, which would suggest that additional composites should lie well below this scale. In this paper we account for the presence of an additional spin 1 custodial triplet of rhos. We examine the implications of requiring perturbative unitarity up to the compositeness scale and find that one has to be close to saturating certain unitarity sum rules involving the Higgs and the rho couplings. Given these restrictions on the parameter space we investigate the main phenomenological consequences of the spin 1 triplet. We find that they can substantially enhance the Higgs di-photon rate at the LHC even with a reduced Higgs coupling to gauge bosons. The main existing LHC bounds arise from di-boson searches, especially in the experimentally clean channel where the charged rhos decay to a W-boson and a Z, which then decay leptonically. We find that a large range of interesting parameter space with 700 GeV < m(rho) < 2 TeV is currently experimentally viable.Comment: 37 pages, 12 figures; v4: sum rule corrected, conclusions unchange

Gas phase Elemental abundances in Molecular cloudS (GEMS) : III. Unlocking the CS chemistry: the CS plus O reaction

Context. Carbon monosulphide (CS) is among the most abundant gas-phase S-bearing molecules in cold dark molecular clouds. It is easily observable with several transitions in the millimeter wavelength range, and has been widely used as a tracer of the gas density in the interstellar medium in our Galaxy and external galaxies. However, chemical models fail to account for the observed CS abundances when assuming the cosmic value for the elemental abundance of sulfur. Aims. The CS+O -> CO + S reaction has been proposed as a relevant CS destruction mechanism at low temperatures, and could explain the discrepancy between models and observations. Its reaction rate has been experimentally measured at temperatures of 150-400 K, but the extrapolation to lower temperatures is doubtful. Our goal is to calculate the CS+O reaction rate at temperatures Methods. We performed ab initio calculations to obtain the three lowest potential energy surfaces (PES) of the CS+O system. These PESs are used to study the reaction dynamics, using several methods (classical, quantum, and semiclassical) to eventually calculate the CS + O thermal reaction rates. In order to check the accuracy of our calculations, we compare the results of our theoretical calculations for T similar to 150-400 K with those obtained in the laboratory. Results. Our detailed theoretical study on the CS+O reaction, which is in agreement with the experimental data obtained at 150-400 K, demonstrates the reliability of our approach. After a careful analysis at lower temperatures, we find that the rate constant at 10 K is negligible, below 10(-15) cm(3) s(-1), which is consistent with the extrapolation of experimental data using the Arrhenius expression. Conclusions. We use the updated chemical network to model the sulfur chemistry in Taurus Molecular Cloud 1 (TMC 1) based on molecular abundances determined from Gas phase Elemental abundances in Molecular CloudS (GEMS) project observations. In our model, we take into account the expected decrease of the cosmic ray ionization rate, zeta(H2), along the cloud. The abundance of CS is still overestimated when assuming the cosmic value for the sulfur abundance.Peer reviewe

SARS-CoV-2 Catalonia contact tracing program : evaluation of key performance indicators

Background: Guidance on SARS-CoV-2 contact tracing indicators have been recently revised by international public health agencies. The aim of the study is to describe and analyse contact tracing indicators based on Catalonia's (Spain) real data and proposing to update them according to recommendations. Methods: Retrospective cohort analysis including Catalonia's contact tracing dataset from 20 May until 31 December 2020. Descriptive statistics are performed including sociodemographic stratification by age, and differences are assessed over the study period. Results: We analysed 923,072 contacts from 301,522 SARS-CoV-2 cases with identified contacts (67.1% contact tracing coverage). The average number of contacts per case was 4.6 (median 3, range 1-243). A total of 403,377 contacts accepted follow-up through three phone calls over a 14-day quarantine period (84.5% of contacts requiring follow-up). The percentage of new cases declared as contacts 14 days prior to diagnosis evolved from 33.9% in May to 57.9% in November. All indicators significantly improved towards the target over time (p < 0.05 for all four indicators). Conclusions: Catalonia's SARS-CoV-2 contact tracing indicators improved over time despite challenging context. The critical revision of the indicator's framework aims to provide essential information in control policies, new indicators proposed will improve system delay's follow-up. The study provides information on COVID-19 indicators framework experience from country's real data, allowing to improve monitoring tools in 2021-2022. With the SARS-CoV-2 pandemic being so harmful to health systems and globally, is important to analyse and share contact tracing data with the scientific community

PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer

Triple-negative breast cancers (TNBCs) have poor prognosis and lack targeted therapies. Here we identified increased copy number and expression of the PIM1 proto-oncogene in genomic data sets of patients with TNBC. TNBC cells, but not nonmalignant mammary epithelial cells, were dependent on PIM1 for proliferation and protection from apoptosis. PIM1 knockdown reduced expression of the anti-apoptotic factor BCL2, and dynamic BH3 profiling of apoptotic priming revealed that PIM1 prevents mitochondrial-mediated apoptosis in TNBC cell lines. In TNBC tumors and their cellular models, PIM1 expression was associated with several transcriptional signatures involving the transcription factor MYC, and PIM1 depletion in TNBC cell lines decreased, in a MYC-dependent manner, cell population growth and expression of the MYC target gene MCL1. Treatment with the pan–PIM kinase inhibitor AZD1208 impaired the growth of both cell line and patient-derived xenografts and sensitized them to standard-of-care chemotherapy. This work identifies PIM1 as a malignant-cell-selective target in TNBC and the potential use of PIM1 inhibitors for sensitizing TNBC to chemotherapy-induced apoptotic cell death

Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C: A prospective observational study

Background: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. Methods: In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with =2 clinical signs/symptoms of NP-C were considered ''suspected NP-C'' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI =70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. Results: In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores =70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. Conclusion: This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis