The predictive validity of the APIL-B in a financial institution.

The purpose of this study was to assess the predictive validity of the APIL test battery, designed to identify learning potential. A sample of 235 successful job applicants completed the APIL Battery and the scores obtained were compared with a set of job success ratings provided by their direct managers. The predictive validity and the use of this psychometric device were assessed within the broad context of the provisions of the Employment Equity Act (55 of 1998), and the manner in which the information about an employee is to be used. The findings are generally positive and their implications are discussed below

К вопросу о значимости дозировки препаратов в ферментозаместительной терапии при болезни Фабри

Болезнь Фабри (БФ) – X-сцепленное заболевание, обусловленное мутациями в гене, кодирующем лизосомальную гидролазу α-галактозидазу А, при котором происходит прогрессирующее накопление в лизосомах глоботриаозилцерамида и связанных гликосфинголипидов. У пациентов мужского пола с классическим фенотипом болезни заболевание клинически манифестирует в детском или подростковом возрасте и характеризуется несколькими симптомами, в том числе нарушением почечной функции, цереброваскулярными осложнениями, сердечной недостаточностью и в конечном счете преждевременной смертью

The first 110,593 COVID-19 patients hospitalised in Lombardy: a regionwide analysis of case characteristics, risk factors and clinical outcomes

Objectives: To describe the monthly distribution of COVID-19 hospitalisations, deaths and case-fatality rates (CFR) in Lombardy (Italy) throughout 2020. Methods: We analysed de-identified hospitalisation data comprising all COVID-19-related admissions from 1 February 2020 to 31 December 2020. The overall survival (OS) from time of first hospitalisation was estimated using the Kaplan-Meier method. We estimated monthly CFRs and performed Cox regression models to measure the effects of potential predictors on OS. Results: Hospitalisation and death peaks occurred in March and November 2020. Patients aged ≥70 years had an up to 180 times higher risk of dying compared to younger patients [70–80: HR 58.10 (39.14–86.22); 80–90: 106.68 (71.01–160.27); ≥90: 180.96 (118.80–275.64)]. Risk of death was higher in patients with one or more comorbidities [1: HR 1.27 (95% CI 1.20–1.35); 2: 1.44 (1.33–1.55); ≥3: 1.73 (1.58–1.90)] and in those with specific conditions (hypertension, diabetes). Conclusion: Our data sheds light on the Italian pandemic scenario, uncovering mechanisms and gaps at regional health system level and, on a larger scale, adding to the body of knowledge needed to inform effective health service planning, delivery, and preparedness in times of crisis

A robust sequential hypothesis testing method for brake squeal localisation

This contribution deals with the in situ detection and localisation of brake squeal in an automobile. As brake squeal is emitted from regions known a priori, i.e., near the wheels, the localisation is treated as a hypothesis testing problem. Distributed microphone arrays, situated under the automobile, are used to capture the directional properties of the sound field generated by a squealing brake. The spatial characteristics of the sampled sound field is then used to formulate the hypothesis tests. However, in contrast to standard hypothesis testing approaches of this kind, the propagation environment is complex and time-varying. Coupled with inaccuracies in the knowledge of the sensor and source positions as well as sensor gain mismatches, modelling the sound field is difficult and standard approaches fail in this case. A previously proposed approach implicitly tried to account for such incomplete system knowledge and was based on ad hoc likelihood formulations. The current paper builds upon this approach and proposes a second approach, based on more solid theoretical foundations, that can systematically account for the model uncertainties. Results from tests in a real setting show that the proposed approach is more consistent than the prior state-of-the-art. In both approaches, the tasks of detection and localisation are decoupled for complexity reasons. The localisation (hypothesis testing) is subject to a prior detection of brake squeal and identification of the squeal frequencies. The approaches used for the detection and identification of squeal frequencies are also presented. The paper, further, briefly addresses some practical issues related to array design and placement. (C) 2019 Author(s)

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Emerging evidence suggests that a small subpopulation of cancer stem cells (CSCs) is responsible for initiation, progression, and metastasis cascade in tumors. CSCs share characteristics with normal stem cells, i.e., self-renewal and differentiation potential, suggesting that they can drive cancer progression. Consequently, targeting CSCs to prevent tumor growth or regrowth might offer a chance to lead the fight against cancer. CSCs create their niche, a specific area within tissue with a unique microenvironment that sustains their vital functions. Interactions between CSCs and their niches play a critical role in regulating CSCs’ self-renewal and tumorigenesis. Differences observed in the frequency of CSCs, due to the phenotypic plasticity of many cancer cells, remain a challenge in cancer therapeutics, since CSCs can modulate their transcriptional activities into a more stem-like state to protect themselves from destruction. This plasticity represents an essential step for future therapeutic approaches. Regarding self-renewal, CSCs are modulated by the same molecular pathways found in normal stem cells, such as Wnt/β-catenin signaling, Notch signaling, and Hedgehog signaling. Another key characteristic of CSCs is their resistance to standard chemotherapy and radiotherapy treatments, due to their capacity to rest in a quiescent state. This review will analyze the primary mechanisms involved in CSC tumorigenesis, with particular attention to the roles of CSCs in tumor progression in benign and malignant diseases; and will examine future perspectives on the identification of new markers to better control tumorigenesis, as well as dissecting the metastasis process

Characterization of early disease status in treatment-naive male paediatric patients with Fabry disease enrolled in a randomized clinical trial.

Trial designThis analysis characterizes the degree of early organ involvement in a cohort of oligo-symptomatic untreated young patients with Fabry disease enrolled in an ongoing randomized, open-label, parallel-group, phase 3B clinical trial.MethodsMales aged 5-18 years with complete α-galactosidase A deficiency, without symptoms of major organ damage, were enrolled in a phase 3B trial evaluating two doses of agalsidase beta. Baseline disease characteristics of 31 eligible patients (median age 12 years) were studied, including cellular globotriaosylceramide (GL-3) accumulation in skin (n = 31) and kidney biopsy (n = 6; median age 15 years; range 13-17 years), renal function, and glycolipid levels (plasma, urine).ResultsPlasma and urinary GL-3 levels were abnormal in 25 of 30 and 31 of 31 patients, respectively. Plasma lyso-GL-3 was elevated in all patients. GL-3 accumulation was documented in superficial skin capillary endothelial cells (23/31 patients) and deep vessel endothelial cells (23/29 patients). The mean glomerular filtration rate (GFR), measured by plasma disappearance of iohexol, was 118.1 mL/min/1.73 m(2) (range 90.4-161.0 mL/min/1.73 m(2)) and the median urinary albumin/creatinine ratio was 10 mg/g (range 4.0-27.0 mg/g). On electron microscopy, renal biopsy revealed GL-3 accumulation in all glomerular cell types (podocytes and parietal, endothelial, and mesangial cells), as well as in peritubular capillary and non-capillary endothelial, interstitial, vascular smooth muscle, and distal tubules/collecting duct cells. Lesions indicative of early Fabry arteriopathy and segmental effacement of podocyte foot processes were found in all 6 patients.ConclusionsThese data reveal that in this small cohort of children with Fabry disease, histological evidence of GL-3 accumulation, and cellular and vascular injury are present in renal tissues at very early stages of the disease, and are noted before onset of microalbuminuria and development of clinically significant renal events (e.g. reduced GFR). These data give additional support to the consideration of early initiation of enzyme replacement therapy, potentially improving long-term outcome.Trial registrationClinicalTrials.gov NCT00701415

Foods for a Mission to Mars: Equivalent System Mass and Development of a Multipurpose Small-Scale Seed Processor

The candidate crops for planetary food systems include: wheat, white and sweet potatoes, soybean, peanut, strawberry, dry bean including le ntil and pinto, radish, rice, lettuce, carrot, green onion, tomato, p eppers, spinach, and cabbage. Crops such as wheat, potatoes, soybean, peanut, dry bean, and rice can only be utilized after processing, while others are classified as ready-to-eat. To process foods in space, the food processing subsystem must be capable of producing a variety of nutritious, acceptable, and safe edible ingredients and food produ cts from pre-packaged and resupply foods as well as salad crops grown on the transit vehicle or other crops grown on planetary surfaces. D esigning, building, developing, and maintaining such a subsystem is b ound to many constraints and restrictions. The limited power supply, storage locations, variety of crops, crew time, need to minimize waste , and other equivalent system mass (ESM) parameters must be considere d in the selection of processing equipment and techniques

Performance of binary prediction models in high-correlation low-dimensional settings:a comparison of methods

BACKGROUND: Clinical prediction models are developed widely across medical disciplines. When predictors in such models are highly collinear, unexpected or spurious predictor-outcome associations may occur, thereby potentially reducing face-validity of the prediction model. Collinearity can be dealt with by exclusion of collinear predictors, but when there is no a priori motivation (besides collinearity) to include or exclude specific predictors, such an approach is arbitrary and possibly inappropriate. METHODS: We compare different methods to address collinearity, including shrinkage, dimensionality reduction, and constrained optimization. The effectiveness of these methods is illustrated via simulations. RESULTS: In the conducted simulations, no effect of collinearity was observed on predictive outcomes (AUC, R(2), Intercept, Slope) across methods. However, a negative effect of collinearity on the stability of predictor selection was found, affecting all compared methods, but in particular methods that perform strong predictor selection (e.g., Lasso). Methods for which the included set of predictors remained most stable under increased collinearity were Ridge, PCLR, LAELR, and Dropout. CONCLUSIONS: Based on the results, we would recommend refraining from data-driven predictor selection approaches in the presence of high collinearity, because of the increased instability of predictor selection, even in relatively high events-per-variable settings. The selection of certain predictors over others may disproportionally give the impression that included predictors have a stronger association with the outcome than excluded predictors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41512-021-00115-5

Simultaneous in-field boost for patients with 1 to 4 brain metastasis/es treated with volumetric modulated arc therapy: a prospective study on quality-of-life

<p>Abstract</p> <p>Purpose</p> <p>To assess treatment toxicity and patients' survival/quality of life (QoL) after volumetric modulated arc therapy (VMAT) with simultaneous in-field boost (SIB) for cancer patients with 1 - 4 brain metastases (BM) treated with or without surgery.</p> <p>Methods and Materials</p> <p>Between March and December 2010, 29 BM patients (total volume BM, < 40 cm³) aged < 80 years, KPS ≥ 70, RPA < III were included in this prospective trial. Whole brain VMAT (30 Gy) and a SIB to the BM (40 Gy) was delivered in 10 fraction. Mean age was 62.1 ± 8.5 years. Fifteen (51.7%) underwent surgery. KPS and MMSE were prospectively assessed. A self-assessed questionnaire was used to assess the QoL (EORTC QLQ-C30 with -BN20 module).</p> <p>Results</p> <p>As of April 2011 and after a mean FU of 5.4 ± 2.8 months, 14 (48.3%) patients died. The 6-month overall survival was 55.1%. Alopecia was only observed in 9 (31%) patients. In 3-month survivors, KPS was significantly (<it>p </it>= 0.01) decreased. MMSE score remained however stable (<it>p </it>= 0.33). Overall, QoL did decrease after VMAT. The mean QLQ-C30 global health status (<it>p </it>= 0.72) and emotional functional (<it>p </it>= 0.91) scores were decreased (low QoL). Physical (<it>p </it>= 0.05) and role functioning score (<it>p </it>= 0.01) were significantly worse and rapidly decreased during treatment. The majority of BN20 domains and single items worsened 3 months after VMAT except headaches (<it>p </it>= 0.046) and bladder control (<it>p </it>= 0.26) which improved.</p> <p>Conclusions</p> <p>The delivery of 40 Gy in 10 fractions to 1 - 4 BM using VMAT was achieved with no significant toxicity. QoL, performance status, but not MMSE, was however compromised 3 months after treatment in this selected cohort of BM patients.</p