Prognostic value of low-level MRD in adult acute lymphoblastic leukemia detected by low- and high-throughput methods

Persistence of minimal residual disease (MRD) after induction/consolidation therapy in acute lymphoblastic leukemia is the leading cause of relapse. The GMALL 07/2003 study used MRD detection by RQ-PCR of clonal immune gene rearrangements with 1x10-4 as discriminating cut-off: levels ≥1x10-4 define molecular failure and MRD-negativity with an assay sensitivity of at least 1x10-4 defines complete molecular response. The clinical relevance of MRD results not fitting in these categories is unclear and termed "molecular not evaluable" (MolNE) towards MRD-based treatment decisions. Within the GMALL 07/03 study, 1019 consecutive bone marrow samples after first consolidation were evaluated for MRD. Patients with complete molecular response had significantly better outcome (five-year overall survival, 5y-OS=85±2%, n=603; five-year disease-free survival, 5y-DFS=73±2%, n=599) compared to patients with molecular failure 5y-OS=40±3%, n=238; 5y-DFS=29±3%, n=208), with MolNE patients in-between (5y-OS=66±4%, 5y-DFS=52±4%, n=178). Of MolNE samples re-analyzed using next-generation sequencing (NGS), patients with undetectable NGS-MRD (n=44; 5y-OS=88±5%, 5y-DFS=70±7%) had significantly better outcome than those with positive NGS-MRD (n=42; 5y-OS=37±8%, 5y-DFS=33±8%). MolNE MRD results are not just borderline values with questionable relevance, but form an intermediate risk group, assignment of which can be further improved by NGS.

Analog and Photon Signal Splicing for CO2-DIAL Based on Piecewise Nonlinear Algorithm

In the CO2 differential absorption lidar (DIAL) system, signals are simultaneously collected through analog detection (AD) and photon counting (PC). These two kinds of signals have their own characteristics. Therefore, a combination of AD and PC signals is of great importance to improve the detection capability (detection range and accuracy) of CO2-DIAL. The traditional signal splicing algorithm cannot meet the accuracy requirements of CO2 inversion due to unreasonable data fitting. In this paper, a piecewise least square splicing algorithm is developed to make signal splicing more flexible and efficient. First, the lidar signal is segmented, and according to the characteristics of each signal, the best fitting parameters are obtained by using the least square fitting with different steps. Then, all the segmented and fitted signals are integrated to realize the effective splicing of the near-field AD signal and the far-field PC signal. A weight gradient strategy is also adopted in signal splicing, and the weights of the AD and PC signals in the spliced signal change with the height. The splicing effect of the improved algorithm is evaluated by the measured signal, which are obtained in Wuhan, China, and the splice of the AD and PC signals in the range of 800–1500 m are completed. Compared with the traditional method, the evaluation parameter R2 and the residual sum of squares of the spliced signal are greatly improved. The linear relationship between the AD and PC signals is improved, and the fitting R2 of differential absorption optical depth reaches 0.909, indicating that the improved signal splicing algorithm can well splice the near-field AD signal and the far-field PC signal.

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SmartKC

Keratoconus is a severe eye disease affecting the cornea (the clear, dome-shaped outer surface of the eye), causing it to become thin and develop a conical bulge. The diagnosis of keratoconus requires sophisticated ophthalmic devices which are non-portable and very expensive. This makes early detection of keratoconus inaccessible to large populations in low-and middle-income countries, making it a leading cause for partial/complete blindness among such populations. We propose SmartKC, a low-cost, smartphone-based keratoconus diagnosis system comprising of a 3D-printed placido's disc attachment, an LED light strip, and an intelligent smartphone app to capture the reflection of the placido rings on the cornea. An image processing pipeline analyzes the corneal image and uses the smartphone's camera parameters, the placido rings' 3D location, the pixel location of the reflected placido rings and the setup's working distance to construct the corneal surface, via the Arc-Step method and Zernike polynomials based surface fitting. In a clinical study with 101 distinct eyes, we found that SmartKC achieves a sensitivity of 87.8% and a specificity of 80.4%. Moreover, the quantitative curvature estimates (sim-K) strongly correlate with a gold-standard medical device (Pearson correlation coefficient = 0.77). Our results indicate that SmartKC has the potential to be used as a keratoconus screening tool under real-world medical settings.

There is More Than Meets the Eye: Identification of Dual Molecular Diagnosis in Patients Affected by Hearing Loss

Hearing loss (HL) is the most common sensory impairment, and it is characterized by a high clinical/genetic heterogeneity. Here we report the identification of dual molecular diagnoses (i.e., mutations at two loci that lead to the expression of two Mendelian conditions) in a series of families affected by non-syndromic and syndromic HL. Eighty-two patients who displayed HL as a major clinical feature have been recruited during the last year. After an accurate clinical evaluation, individuals have been analyzed through whole-exome sequencing (WES). This protocol led to the identification of seven families characterized by the presence of a dual diagnosis. In particular, based on the clinical and genetic findings, patients have been classified into two groups: a) patients with HL and distinct phenotypes not fitting in a known syndrome due to mutations at two loci (e.g., HL in association with Marfan syndrome) and b) patients with two genes involved in HL phenotype (e.g., TMPRSS3 and MYH14). These data highlight for the first time the high prevalence of dual molecular diagnoses in HL patients and suggest that they should be considered especially for those cases that depart from the expected clinical manifestation or those characterized by a significant intra-familiar variability.

Analyzing the Fitting of Novel Preformed Osteosynthesis Plates for the Reduction and Fixation of Mandibular Fractures

Purpose: The known preformed osteosynthesis plates for the midface are helpful tools for a precise and fast fixation of repositioned fractures. The purpose of the current study is to analyze the precision of newly developed prototypes of preformed osteosynthesis plates for the mandible. Methods: Four newly designed preformed osteosynthesis plates, generated by a statistical shape model based on 115 CT scans, were virtually analyzed. The used plates were designed for symphyseal, parasymphyseal, angle, and condyle fractures. Each type of plate has three different sizes. For analysis, the shortest distance between the plate and the bone surface was measured, and the sum of the plate-to-bone distances over the whole surface was calculated. Results: A distance between plate and bone of less than 1.5 mm was defined as sufficient fitting. The plate for symphyseal fractures showed good fitting in 90% of the cases for size M, and in 84% for size L. For parasymphyseal fractures, size S fits in 80%, size M in 68%, and size L in 65% of the cases. Angle fractures with their specific plate show good fitting for size S in 53%, size M in 60%, and size L in 47%. The preformed plate for the condyle part fits for size S in 75%, for size M in 85%, and for size L in 74% of the cases. Conclusion: The newly developed mandible plates show sufficient clinical fitting to ensure adequate fracture reduction and fixation.

Calcatedessa gen.n. a new genus sister to Grammedessa Correia & Fernandes (Heteroptera, Pentatomidae, Edessinae) based on a cladistic analysis

Grammedessa Correia & Fernandes, 2016 is a genus raised to include some species of Edessa Fabricius, 1803 that is a very common group of stink bugs inhabiting only the Neotropical region. Grammedessa was proposed excluding a few species that were morphologically similar but not completely fitting in the diagnostic requirements of the genus. Grammedessa was also proposed without considering a phylogenetic context. In this work, the monophyly of Grammedessa was tested using a cladistic analysis, including all species that were originally excluded, under both Maximum Parsimony and Bayesian methods. As a result, six new species are now included in Grammedessa, which will be described in a forthcoming paper; Edessa botocudo Kirkaldy, 1909 was considered an unnecessary new name for Edessa hamata Walker, 1868 that was transferred to Grammedessa, resulting in G. hamata (Walker, 1868) comb.n. Calcatedessa gen.n., a new genus sister to Grammedessa, is here proposed to include four new species: C. anthomorpha sp.n., C. clarimarginata sp.n., C. germana sp.n. and C. temnomarginata sp.n. The Calcatedessa–Grammedessa clade and both genera were recovered as monophyletic by Maximum Parsimony and Bayesian methods. An identification key to the species of Calcatedessa gen.n. is provided. The new genus is distributed in Guyana, Suriname, French Guyana, and Brazil.

Ethical leadership and public accountability: Problematiques of South Africa’s State-Owned Enterprises

This paper aims to explore the potency of ethical frameworks in the advent of a democratic dispensation in State-Owned Enterprises in an attempt to address conundrums of unethical leadership and devastating public accountability. This paper argues that South Africa is grappling with fitting in the notion of ethos and accountability. On the same line, the contestation about the impasse of the State-Owned Enterprises (SOEs) befits germane in the topical and constant political transformation in South Africa. SOEs endure eccentric to those serving it and those who benefit from it, leading to a lack of orthodoxy by public officials to ethical framework prescribed and contemplated in legislation for good conduct in public services. Ethical leadership and public accountability are two sides of the same coin; however, they serve as a nut and bolt of a well-functioning public administration. The two are inseparable. The paper is theoretical as such, and it is epistemologically juxtaposed and grounded or underpinned by agency theory and its ideals. Be that as it may, it further depends on literature base review for its premise, argument, crux, and purpose and drawing up results and conclusion. Thus, the paper gathers information regarding the various scholars’ notions on ethical leadership and public accountability from related articles, journals, and books. The paper reveals that the South African State-Owned Enterprises are antagonized and branded by unethical leaders and public accountability challenges. At this juncture, the SOEs are faced with poor fiscal coordination and management. The paper further reveals that the SOEs are swimming in the pool of debts. The conclusion that can be deduced from this paper is that it calls for strengthening and reforming all legislative prescripts that govern the State-Owned Enterprises. Public administrators must avoid incubating politicians as it creates the ground for corruption and various types of ethical dilemmas.