1,675 research outputs found

    Parkinson disease clinical subtypes: Key features & clinical milestones

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    OBJECTIVES: Based on multi-domain classification of Parkinson disease (PD) subtypes, we sought to determine the key features that best differentiate subtypes and the utility of PD subtypes to predict clinical milestones. METHODS: Prospective cohort of 162 PD participants with ongoing, longitudinal follow-up. Latent class analysis (LCA) delineated subtypes based on score patterns across baseline motor, cognitive, and psychiatric measures. Discriminant analyses identified key features that distinguish subtypes at baseline. Cox regression models tested PD subtype differences in longitudinal conversion to clinical milestones, including deep brain stimulation (DBS), dementia, and mortality. RESULTS: LCA identified distinct subtypes: motor only (N = 63) characterized by primary motor deficits; psychiatric & motor (N = 17) characterized by prominent psychiatric symptoms and moderate motor deficits; cognitive & motor (N = 82) characterized by impaired cognition and moderate motor deficits. Depression, executive function, and apathy best discriminated subtypes. Since enrollment, 22 had DBS, 48 developed dementia, and 46 have died. Although there were no subtype differences in rate of DBS, dementia occurred at a higher rate in the cognitive & motor subtype. Surprisingly, mortality risk was similarly elevated for both cognitive & motor and psychiatric & motor subtypes compared to the motor only subtype (relative risk = 3.15, 2.60). INTERPRETATION: Psychiatric and cognitive features, rather than motor deficits, distinguish clinical PD subtypes and predict greater risk of subsequent dementia and mortality. These results emphasize the value of multi-domain assessments to better characterize clinical variability in PD. Further, differences in dementia and mortality rates demonstrate the prognostic utility of PD subtypes

    Thin-Skin Electromagnetic Fields Around Surface-Breaking Cracks in Metals

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    In situations where the electrical skin depth δ is small compared with a typical crack dimension l, substantial progress has been achieved in recent years in modeling surface electromagnetic fields and the perturbations that are produced in them by surface-breaking flaws [1,2,3]. The development of an unfolding theory at UCL for thin-skin surface fields was based on the approximation that the electric and magnetic field vectors E and H are essentially tangential to the surface of the material in the surface skin. It was motivated by the desire to measure fatigue cracks in ferrous materials used in large-scale steel structures such as offshore oil rigs [2], and the method to which it was applied was the a.c. field measurement technique. Auld et al [4,5] later adapted the unfolding approach in considering thin-skin field models for the eddy current method, and their major concern was with applications to non-ferrous materials used in airframe and aero-engine manufacture. For acfm work, the unfolding theory leads to a surface Laplacian field on both the metal surface and the crack face and information on the crack presence is deduced by measuring perturbations in the surface field. Auld’s model for eddy currents also has a plane Laplacian field on the crack face, but it is assumed that the crack produces no change in the field on the metal surface. Field lines in the unfolded plane for both models are shown schematically in Figure 1(b,c) for the case when the interrogating field is uniform and the crack is semi-circular. Auld’s model has been described as a Born type of approximation from an analogy with wave scattering theory which ignores the scattered field when calculating scattering cross-sections

    Bianchi Type-II String Cosmological Models in Normal Gauge for Lyra's Manifold with Constant Deceleration Parameter

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    The present study deals with a spatially homogeneous and anisotropic Bianchi-II cosmological models representing massive strings in normal gauge for Lyra's manifold by applying the variation law for generalized Hubble's parameter that yields a constant value of deceleration parameter. The variation law for Hubble's parameter generates two types of solutions for the average scale factor, one is of power-law type and other is of the exponential form. Using these two forms, Einstein's modified field equations are solved separately that correspond to expanding singular and non-singular models of the universe respectively. The energy-momentum tensor for such string as formulated by Letelier (1983) is used to construct massive string cosmological models for which we assume that the expansion (θ\theta) in the model is proportional to the component σ 11\sigma^{1}_{~1} of the shear tensor σij\sigma^{j}_{i}. This condition leads to A=(BC)mA = (BC)^{m}, where A, B and C are the metric coefficients and m is proportionality constant. Our models are in accelerating phase which is consistent to the recent observations. It has been found that the displacement vector β\beta behaves like cosmological term Λ\Lambda in the normal gauge treatment and the solutions are consistent with recent observations of SNe Ia. It has been found that massive strings dominate in the decelerating universe whereas strings dominate in the accelerating universe. Some physical and geometric behaviour of these models are also discussed.Comment: 24 pages, 10 figure

    Muscle UCP-3 mRNA levels are elevated in weight loss associated with gastrointestinal adenocarcinoma in humans

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    The mitochondrial uncoupling proteins-2 and -3 are putative mediators of thermogenesis and energy expenditure. We measured the mRNA levels of uncoupling proteins-2 and -3 in skeletal muscle from 12 gastrointestinal adenocarcinoma patients, of whom six had stable weight and six had lost 2–18 kg, and from six healthy controls undergoing elective surgery. Uncoupling proteins-3 mRNA levels were significantly higher in the muscle of the cancer patients with weight loss (2.2±0.47 arbitrary units) compared both with controls (0.39±0.20) and with cancer patients who had not lost weight (0.47±0.23; P<0.02). Uncoupling proteins-2 mRNA levels did not differ significantly between groups. Elevations in muscle uncoupling proteins-3 activity may enhance energy expenditure and this in turn could contribute to tissue catabolism

    McCune-Albright syndrome

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    McCune-Albright syndrome (MAS) is classically defined by the clinical triad of fibrous dysplasia of bone (FD), café-au-lait skin spots, and precocious puberty (PP). It is a rare disease with estimated prevalence between 1/100,000 and 1/1,000,000. FD can involve a single or multiple skeletal sites and presents with a limp and/or pain, and, occasionally, a pathologic fracture. Scoliosis is common and may be progressive. In addition to PP (vaginal bleeding or spotting and development of breast tissue in girls, testicular and penile enlargement and precocious sexual behavior in boys), other hyperfunctioning endocrinopathies may be involved including hyperthyroidism, growth hormone excess, Cushing syndrome, and renal phosphate wasting. Café-au-lait spots usually appear in the neonatal period, but it is most often PP or FD that brings the child to medical attention. Renal involvement is seen in approximately 50% of the patients with MAS. The disease results from somatic mutations of the GNAS gene, specifically mutations in the cAMP regulating protein, Gs alpha. The extent of the disease is determined by the proliferation, migration and survival of the cell in which the mutation spontaneously occurs during embryonic development. Diagnosis of MAS is usually established on clinical grounds. Plain radiographs are often sufficient to make the diagnosis of FD and biopsy of FD lesions can confirm the diagnosis. The evaluation of patients with MAS should be guided by knowledge of the spectrum of tissues that may be involved, with specific testing for each. Genetic testing is possible, but is not routinely available. Genetic counseling, however, should be offered. Differential diagnoses include neurofibromatosis, osteofibrous dysplasia, non-ossifying fibromas, idiopathic central precocious puberty, and ovarian neoplasm. Treatment is dictated by the tissues affected, and the extent to which they are affected. Generally, some form of surgical intervention is recommended. Bisphosphonates are frequently used in the treatment of FD. Strengthening exercises are recommended to help maintaining the musculature around the FD bone and minimize the risk for fracture. Treatment of all endocrinopathies is required. Malignancies associated with MAS are distinctly rare occurrences. Malignant transformation of FD lesions occurs in probably less than 1% of the cases of MAS

    Targeting the X Chromosome during Spermatogenesis Induces Y Chromosome Transmission Ratio Distortion and Early Dominant Embryo Lethality in Anopheles gambiae

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    We have exploited the high selectivity of the homing endonuclease I-PpoI for the X-linked Anopheles gambiae 28S ribosomal genes to selectively target X chromosome carrying spermatozoa. Our data demonstrated that in heterozygous males, the expression of I-PpoI in the testes induced a strong bias toward Y chromosome–carrying spermatozoa. Notably, these male mosquitoes also induced complete early dominant embryo lethality in crosses with wild-type females. Morphological and molecular data indicated that all spermatozoa, irrespectively of the inheritance of the transgene, carried a substantial amount of I-PpoI protein that could attack the maternally inherited chromosome X of the embryo. Besides the obvious implications for implementing vector control measures, our data demonstrated the feasibility of generating synthetic sex distorters and revealed the intriguing possibility of manipulating maternally inherited genes using wild-type sperm cells carrying engineered endonucleases

    Targeting the X Chromosome during Spermatogenesis Induces Y Chromosome Transmission Ratio Distortion and Early Dominant Embryo Lethality in Anopheles gambiae

    Get PDF
    We have exploited the high selectivity of the homing endonuclease I-PpoI for the X-linked Anopheles gambiae 28S ribosomal genes to selectively target X chromosome carrying spermatozoa. Our data demonstrated that in heterozygous males, the expression of I-PpoI in the testes induced a strong bias toward Y chromosome–carrying spermatozoa. Notably, these male mosquitoes also induced complete early dominant embryo lethality in crosses with wild-type females. Morphological and molecular data indicated that all spermatozoa, irrespectively of the inheritance of the transgene, carried a substantial amount of I-PpoI protein that could attack the maternally inherited chromosome X of the embryo. Besides the obvious implications for implementing vector control measures, our data demonstrated the feasibility of generating synthetic sex distorters and revealed the intriguing possibility of manipulating maternally inherited genes using wild-type sperm cells carrying engineered endonucleases
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