Screening for congenital hypothyroidism in Maltese newborns using cord blood

Routine screening for congenital hypothyroidism (CHT) has been introduced because clinical features of CHT may not be evident before the baby is a few weeks old and treatment at this stage may already be too late. Since a newborn testing programme employing liquid cord blood for other conditions had already been developed in the University of Malta and the Department of Health, we explored the possibility of implementing newborn thyroid testing using liquid cord blood. A similar programme had been implemented successfully in Finland and Philadelphia. Between September 1989 and August 1995 around 32,000 newborns were tested. This is nearly complete ascertainment. Preliminary testing was by radioimmunoassay for TSH. The sera of those with TSH levels more than 13mU/l were further tested for free T4. If the free T4 level was below 12 pmol/l, the babies were recalled for clinical evaluation and repeat testing. Other babies were recalled for technical reasons, giving a total recall rate of 3.88%. CHT was identified in seven newborns and treatment started within 3 weeks of delivery. One baby was reported normal on screening but was suspected to have CHT on clinical grounds at 3 weeks of age, confirmed biochemically. The incidence of CHT in Malta is therefore 1 in 4500.peer-reviewe

Kinematics: On Direction Cosine Matrices

Motion mechanics (dynamics) comprises kinetics to describe the implications of applied forces and torques; and also kinematics (phoronomics). Developed in the 1700s, kinematics describes mathematical translations from one basis of measurement to another using common kinematic measurement variables like quaternions, Euler angles, and direction cosine matrices. Two ubiquitous rotation sequences are unquestionably adopted for developing modern direction cosine matrices from among the 12 potential options, stemming from applicability to aerospace systems, accuracy, and computation burden. This chapter provides a comprehensive reevaluation of all 12 options yielding a menu of options for accuracy and computational burdens, with the results illustrated compared to the ubiquitous two modernly adopted choices, broken into two rotational groups: symmetric rotations and nonsymmetric rotations. Validation will be provided by critical analysis of integration using step size to illustrate correlated minimal accuracy. No single rotational sequence is universally superior with respect to all figures of merit, enabling trade-space analysis between rotational sequences. One interesting revelation of one of the two ubiquitous sequences (the 3-1-3 symmetric sequence) is illustrated to have relatively less accuracy but lower computational burden than the other (the 3-2-1 nonsymmetric sequence). Meanwhile, a relatively unknown “2-3-1” rotational sequence is shown to have similar computational burden and accuracy

Modern Control System Learning

This manuscript will explore and analyze the effects of different controllers in an overall spacecraft’s attitude determination and control system (ADCS). The experimental setup will include comparing an ideal nonlinear feedforward controller, a feedback controller, and a combined ideal nonlinear feedforward + feedback controller within a Simulink simulation. A custom proportional, derivative, integral controller was implemented in the feedback control, adding an additional term to account for the nonlinear coupled motion. Consistent proportional, derivative, and integral gains were used throughout the duration of the experiment. The simulated results will show that the ideal nonlinear feedforward controller lacked an error correction mechanism and took extra time to execute, the feedback controller faired only slightly better, but the combined ideal nonlinear feedforward controller with feedback correction yielded the highest accuracy with the lowest execution time. This highlights the potential effectiveness for a learning control system

Optimal Learning and Self-Awareness Versus PDI

The article of record as published may be found at�https://doi.org/10.3390/a13010023This manuscript will explore and analyze the effects of different paradigms for the control of rigid body motion mechanics. The experimental setup will include deterministic artificial intelligence composed of optimal self-awareness statements together with a novel, optimal learning algorithm, and these will be re-parameterized as ideal nonlinear feedforward and feedback evaluated within a Simulink simulation. Comparison is made to a custom proportional, derivative, integral controller (modified versions of classical proportional-integral-derivative control) implemented as a feedback control with a specific term to account for the nonlinear coupled motion. Consistent proportional, derivative, and integral gains were used throughout the duration of the experiments. The simulation results will show that akin feedforward control, deterministic self-awareness statements lack an error correction mechanism, relying on learning (which stands in place of feedback control), and the proposed combination of optimal self-awareness statements and a newly demonstrated analytically optimal learning yielded the highest accuracy with the lowest execution time. This highlights the potential effectiveness of a learning control system

Identification of an HNF1A p.Gly292fs frameshift mutation presenting as diabetes during pregnancy in a Maltese family

The diagnosis of maturity onset diabetes of the young (MODY) is a challenging process in view of the extensive clinical and genetic heterogeneity of the disease. Mutations in the gene encoding hepatocyte nuclear factor 1α (HNF1A) are responsible for most forms of monogenic diabetes in Northern European populations. Genetic analysis through a combination of whole exome sequencing and Sanger sequencing in three Maltese siblings and their father identified a rare duplication/frameshift mutation in exon 4 of HNF1A that lies within a known mutational hotspot in this gene. In this report, we provide the first description of an HNF1A-MODY3 phenotype in a Maltese family. The findings reported are relevant and new to a regional population, where the epidemiology of atypical diabetes has never been studied before. This report is of clinical interest as it highlights how monogenic diabetes can be misdiagnosed as either type 1, type 2, or gestational diabetes. It also reinforces the need for a better characterisation of monogenic diabetes in Mediterranean countries, particularly in island populations such as Malta with a high prevalence of diabetes.peer-reviewe

Presence of Skin α-Synuclein Deposits Discriminates Parkinson's Disease from Progressive Supranuclear Palsy and Corticobasal Syndrome

Background: Previous studies reported skin phosphorylated α-synuclein (p-syn) deposits in Parkinson's disease (PD) patients but not in patients with parkinsonism due to tauopathies, although data on the latter are limited. Objective: We aimed to assess the presence of skin p-syn deposits in patients with clinical diagnosis of parkinsonism usually due to tauopathy and PD. Methods: We consecutively recruited 26 patients, 18 fulfilling clinical diagnostic criteria of progressive supranuclear palsy (PSP) and 8 of corticobasal syndrome (CBS), 26 patients with PD, and 26 healthy controls (HC). All subjects underwent skin biopsy to study p-syn deposits in skin nerves by immunofluorescence. Results: Skin p-syn deposits were present in only two of the PSP/CBS patients and none of the HC. Conversely, all PD patients showed p-syn deposition (p <  0.001, Chi-square). The two p-syn positive patients were diagnosed with PSP and CBS, respectively. Although clinical and MRI findings supported these diagnoses, both patients had some atypical features more typical of synucleinopathies. Conclusion: The detection of skin p-syn deposits may help in the differential diagnosis of parkinsonism. Indeed, in this study, all PD patients and only two out of 26 with a clinical diagnosis of PSP/CBS had skin p-syn deposits. Furthermore, these two patients showed clinical features that could suggest an atypical synucleinopathy presentation or a mixed pathology

Reactive oxygen species and its role in pathogenesis and resistance to therapy in acute myeloid leukemia

Relapse following a short clinical response to therapy is the major challenge for the management of acute myeloid leukemia (AML) patients. Leukemic stem cells (LSC), as the source of relapse, have been investigated for their metabolic preferences and their alterations at the time of relapse. As LSC rely on oxidative phosphorylation (OXPHOS) for energy requirement, reactive oxygen species (ROS), as by-products of OXPHOS, have been investigated for their role in the effectiveness of the standard AML therapy. Increased levels of non-mitochondrial ROS, generated by nicotinamide adenine dinucleotide phosphate oxidase, in a subgroup of AML patients add to the complexity of studying ROS. Although there are various studies presenting the contribution of ROS to AML pathogenesis, resistance, and its inhibition or activation as a target, a model that can clearly explain its role in AML has not been conceptualized. This is due to the heterogeneity of AML, the dynamics of ROS production, which is influenced by factors such as the type of treatment, cell differentiation state, mitochondrial activity, and also the heterogeneous generation of non-mitochondrial ROS and limited available data on their interaction with the microenvironment. This review summarizes these challenges and the recent progress in this field

Dark Matter in the Coming Decade: Complementary Paths to Discovery and Beyond

In this report we summarize the many dark matter searches currently being pursued through four complementary approaches: direct detection, indirect detection, collider experiments, and astrophysical probes. The essential features of broad classes of experiments are described, each with their own strengths and weaknesses. The complementarity of the different dark matter searches is discussed qualitatively and illustrated quantitatively in two simple theoretical frameworks. Our primary conclusion is that the diversity of possible dark matter candidates requires a balanced program drawing from all four approaches.Comment: Report prepared for the Community Summer Study (Snowmass) 2013, on behalf of Cosmic Frontier Working Groups 1-4 (CF1: WIMP Dark Matter Direct Detection, CF2: WIMP Dark Matter Indirect Detection, CF3: Non-WIMP Dark Matter, and CF4: Dark Matter Complementarity); published versio

Electroweak symmetry breaking after LEP1 and LEP2

In a generic 'universal' theory of electroweak symmetry breaking, non fine-tuned heavy new physics affects the low-energy data through four parameters, which include and properly extend the generally insufficient S and T. Only by adding the LEP2 data to the global electroweak fit, can all these four form factors be determined and deviations from the SM be strongly constrained. Several of the recently proposed models (little Higgs, gauge bosons in extra dimensions or Higgsless models in 5D) are recognized to be 'universal' in a straightforward way after a proper definition of the effective vector boson fields. Among various applications, we show that proposed Higgsless models in 5D, when calculable, do not provide a viable description of electroweak symmetry breaking in their full range of parameters.Comment: 16 pages, 5 figures. Ref.s added, discussion of low energy observables improve