Xeroderma Pigmentosum

Xeroderma pigmentosum (XP) is defined by extreme sensitivity to sunlight, resulting in sunburn, pigment changes in the skin and a greatly elevated incidence of skin cancers. It is a rare autosomal recessive disorder and has been found in all continents and racial groups. Estimated incidences vary from 1 in 20, 000 in Japan to 1 in 250, 000 in the USA, and approximately 2.3 per million live births in Western Europe. The first features are either extreme sensitivity to sunlight, triggering severe sunburn, or, in patients who do not show this sun-sensitivity, abnormal lentiginosis (freckle-like pigmentation due to increased numbers of melanocytes) on sun-exposed areas. This is followed by areas of increased or decreased pigmentation, skin aging and multiple skin cancers, if the individuals are not protected from sunlight. A minority of patients show progressive neurological abnormalities. There are eight XP complementation groups, corresponding to eight genes, which, if defective, can result in XP. The products of these genes are involved in the repair of ultraviolet (UV)- induced damage in DNA. Seven of the gene products (XPA through G) are required to remove UV damage from the DNA. The eighth (XPV or DNA polymerase h) is required to replicate DNA containing unrepaired damage. There is wide variability in clinical features both between and within XP groups. Diagnosis is made clinically by the presence, from birth, of an acute and prolonged sunburn response at all exposed sites, unusually early lentiginosis in sun-exposed areas or onset of skin cancers at a young age. The clinical diagnosis is confirmed by cellular tests for defective DNA repair. These features distinguish XP from other photodermatoses such as solar urticaria and polymorphic light eruption, Cockayne Syndrome (no pigmentation changes, different repair defect) and other lentiginoses such as Peutz-Jeghers syndrome, Leopard syndrome and Carney complex (pigmentation not sunassociated), which are inherited in an autosomal dominant fashion. Antenatal diagnosis can be performed by measuring DNA repair or by mutation analysis in CVS cells or in amniocytes. Although there is no cure for XP, the skin effects can be minimised by rigorous protection from sunlight and early removal of pre-cancerous lesions. In the absence of neurological problems and with lifetime protection against sunlight, the prognosis is good. In patients with neurological problems, these are progressive, leading to disabilities and a shortened lifespan

Stepping stability: effects of sensory perturbation

BACKGROUND: Few tools exist for quantifying locomotor stability in balance impaired populations. The objective of this study was to develop and evaluate a technique for quantifying stability of stepping in healthy people and people with peripheral (vestibular hypofunction, VH) and central (cerebellar pathology, CB) balance dysfunction by means a sensory (auditory) perturbation test. METHODS: Balance impaired and healthy subjects performed a repeated bench stepping task. The perturbation was applied by suddenly changing the cadence of the metronome (100 beat/min to 80 beat/min) at a predetermined time (but unpredictable by the subject) during the trial. Perturbation response was quantified by computing the Euclidian distance, expressed as a fractional error, between the anterior-posterior center of gravity attractor trajectory before and after the perturbation was applied. The error immediately after the perturbation (Emax), error after recovery (Emin) and the recovery response (Edif) were documented for each participant, and groups were compared with ANOVA. RESULTS: Both balance impaired groups exhibited significantly higher Emax (p = .019) and Emin (p = .028) fractional errors compared to the healthy (HE) subjects, but there were no significant differences between CB and VH groups. Although response recovery was slower for CB and VH groups compared to the HE group, the difference was not significant (p = .051). CONCLUSION: The findings suggest that individuals with balance impairment have reduced ability to stabilize locomotor patterns following perturbation, revealing the fragility of their impairment adaptations and compensations. These data suggest that auditory perturbations applied during a challenging stepping task may be useful for measuring rehabilitation outcomes

Composite undergraduate clinical examinations: how should the components be combined to maximize reliability?

Background: Clinical examinations increasingly consist of composite tests to assess all aspects of the curriculum recommended by the General Medical Council. Setting: A final undergraduate medical school examination for 214 students. Aim: To estimate the overall reliability of a composite examination, the correlations between the tests, and the effect of differences in test length, number of items and weighting of the results on the reliability. Method: The examination consisted of four written and two clinical tests: multiple-choice questions (MCQ) test, extended matching questions (EMQ), shortanswer questions (SAQ), essays, an objective structured clinical examination (OSCE) and history-taking long cases. Multivariate generalizability theory was used to estimate the composite reliability of the examination and the effects of item weighting and test length. Results: The composite reliability of the examination was 0-77, if all tests contributed equally. Correlations between examination components varied, suggesting that different theoretically interpretable parameters of competence were being tested. Weighting tests according to items per test or total test time gave improved reliabilities of 0-93 and 0-81, respectively. Double weighting of the clinical component marginally affected the reliability (0-76). Conclusion: This composite final examination achieved an overall reliability sufficient for high-stakes decisions on student clinical competence. However, examination structure must be carefully planned and results combined with caution. Weighting according to number of items or test length significantly affected reliability. The components testing different aspects of knowledge and clinical skills must be carefully balanced to ensure both content validity and parity between items and test length.Selección de trabajos ya publicados sobre los que se trabajó en los talleres de las Jornadas de Educación MédicaSociedad de Educación Medica de La Plat

Tai Chi and vestibular rehabilitation improve vestibulopathic gait via different neuromuscular mechanisms: Preliminary report

BACKGROUND: Vestibular rehabilitation (VR) is a well-accepted exercise program intended to remedy balance impairment caused by damage to the peripheral vestibular system. Alternative therapies, such as Tai Chi (TC), have recently gained popularity as a treatment for balance impairment. Although VR and TC can benefit people with vestibulopathy, the degree to which gait improvements may be related to neuromuscular adaptations of the lower extremities for the two different therapies are unknown. METHODS: We examined the relationship between lower extremity neuromuscular function and trunk control in 36 older adults with vestibulopathy, randomized to 10 weeks of either VR or TC exercise. Time-distance measures (gait speed, step length, stance duration and step width), lower extremity sagittal plane mechanical energy expenditures (MEE), and trunk sagittal and frontal plane kinematics (peak and range of linear and angular velocity), were measured. RESULTS: Although gait time-distance measures were improved in both groups following treatment, no significant between-groups differences were observed for the MEE and trunk kinematic measures. Significant within groups changes, however, were observed. The TC group significantly increased ankle MEE contribution and decreased hip MEE contribution to total leg MEE, while no significant changes were found within the VR group. The TC group exhibited a positive relationship between change in leg MEE and change in trunk velocity peak and range, while the VR group exhibited a negative relationship. CONCLUSION: Gait function improved in both groups consistent with expectations of the interventions. Differences in each group's response to therapy appear to suggest that improved gait function may be due to different neuromuscular adaptations resulting from the different interventions. The TC group's improvements were associated with reorganized lower extremity neuromuscular patterns, which appear to promote a faster gait and reduced excessive hip compensation. The VR group's improvements, however, were not the result of lower extremity neuromuscular pattern changes. Lower-extremity MEE increases corresponded to attenuated forward trunk linear and angular movement in the VR group, suggesting better control of upper body motion to minimize loss of balance. These data support a growing body of evidence that Tai Chi may be a valuable complementary treatment for vestibular disorders

Effects of Space Charge, Dopants, and Strain Fields on Surfaces and Grain Boundaries in YBCO Compounds

Statistical thermodynamical and kinetically-limited models are applied to study the origin and evolution of space charges and band-bending effects at low angle [001] tilt grain boundaries in YBa$_2$Cu$_3$O$_7$ and the effects of Ca doping upon them. Atomistic simulations, using shell models of interatomic forces, are used to calculate the energetics of various relevant point defects. The intrinsic space charge profiles at ideal surfaces are calculated for two limits of oxygen contents, i.e. YBa$_2$Cu$_3$O$_6$ and YBa$_2$Cu$_3$O$_7$. At one limit, O$_6$, the system is an insulator, while at O$_7$, a metal. This is analogous to the intrinsic and doping cases of semiconductors. The site selections for doping calcium and creating holes are also investigated by calculating the heat of solution. In a continuum treatment, the volume of formation of doping calcium at Y-sites is computed. It is then applied to study the segregation of calcium ions to grain boundaries in the Y-123 compound. The influences of the segregation of calcium ions on space charge profiles are finally studied to provide one guide for understanding the improvement of transport properties by doping calcium at grain boundaries in Y-123 compound.Comment: 13 pages, 5 figure

Isotropic three-dimensional T₂ mapping of knee cartilage: Development and validation.

1) To implement a higher-resolution isotropic 3D T <sub>2</sub> mapping technique that uses sequential T <sub>2</sub> -prepared segmented gradient-recalled echo (Iso3DGRE) images for knee cartilage evaluation, and 2) to validate it both in vitro and in vivo in healthy volunteers and patients with knee osteoarthritis. The Iso3DGRE sequence with an isotropic 0.6 mm spatial resolution was developed on a clinical 3T MR scanner. Numerical simulations were performed to optimize the pulse sequence parameters. A phantom study was performed to validate the T <sub>2</sub> estimation accuracy. The repeatability of the sequence was assessed in healthy volunteers (n = 7). T <sub>2</sub> values were compared with those from a clinical standard 2D multislice multiecho (MSME) T <sub>2</sub> mapping sequence in knees of healthy volunteers (n = 13) and in patients with knee osteoarthritis (OA, n = 5). The numerical simulations resulted in 100 excitations per segment and an optimal radiofrequency (RF) excitation angle of 15°. The phantom study demonstrated a good correlation of the technique with the reference standard (slope 0.9 ± 0.05, intercept 0.2 ± 1.7 msec, R <sup>2</sup> ≥ 0.99). Repeated measurements of cartilage T <sub>2</sub> values in healthy volunteers showed a coefficient of variation of 5.6%. Both Iso3DGRE and MSME techniques found significantly higher cartilage T <sub>2</sub> values (P < 0.03) in OA patients. Iso3DGRE precision was equal to that of the MSME T <sub>2</sub> mapping in healthy volunteers, and significantly higher in OA (P = 0.01). This study successfully demonstrated that high-resolution isotropic 3D T <sub>2</sub> mapping for knee cartilage characterization is feasible, accurate, repeatable, and precise. The technique allows for multiplanar reformatting and thus T <sub>2</sub> quantification in any plane of interest. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:362-371

[Letter] A distinct genotype of XP complementation group A: surprisingly mild phenotype highly prevalent in Northern India/ Pakistan/ Afghanistan

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Simultaneous fat-free isotropic 3D anatomical imaging and T₂ mapping of knee cartilage with lipid-insensitive binomial off-resonant RF excitation (LIBRE) pulses.

Improved knee cartilage morphological delineation and T <sub>2</sub> mapping precision necessitates isotropic 3D high-resolution and efficient fat suppression. To develop and assess an isotropic 3D lipid-insensitive T <sub>2</sub> mapping technique of the knee for improved cartilage delineation and precise measurement of T <sub>2</sub> relaxation times. Prospective. Phantoms (n = 6) used in this study were designed to mimic the T <sub>1</sub> and T <sub>2</sub> relaxation times of cartilage and fat. The study cohort comprised healthy volunteers (n = 7) for morphometry and T <sub>2</sub> relaxation time measurements. A high-resolution isotropic 3D T <sub>2</sub> mapping technique that uses sequential T <sub>2</sub> -prepared segmented gradient-recalled echo (Iso3DGRE) images and lipid-insensitive binomial off-resonant radiofrequency (RF) excitation (LIBRE) at 3T. Numerical simulations and phantom experiments were performed to optimize the LIBRE pulse. Phantom studies were carried out to test the accuracy of the technique against reference standard spin-echo (SE) T <sub>2</sub> mapping. Subsequently, T <sub>2</sub> maps with and without LIBRE pulses were acquired in knees of healthy volunteers and the T <sub>2</sub> relaxation time values in different cartilage compartments were compared. A two-tailed paired Student's t-test was used to compare the average T <sub>2</sub> values and the relative standard deviations (inverse measurement of the precision) obtained with and without LIBRE pulses. A LIBRE pulse of 1 msec suppressed fat with an RF excitation frequency offset of 1560 Hz and optimal RF excitation angle of 35°. These results were corroborated by phantom and knee experiments. Robust and homogeneous fat suppression was obtained (a fat signal-to-noise ratio (SNR) decrease of 86.4 ± 2.4%). In phantoms, T <sub>2</sub> values were found in good agreement when comparing LIBRE-Iso3DGRE with SE (slope 0.93 ± 0.04, intercept 0.11 ± 1.6 msec, R <sup>2</sup> >0.99). In vivo, LIBRE excitation resulted in more precise T <sub>2</sub> estimation (23.7 ± 7.4%) than normal excitation (30.5 ± 9.9%, P < 0.0001). Homogeneous LIBRE fat signal suppression was achieved with a total RF pulse duration of 1 msec, allowing for the removal of chemical shift artifacts and resulting in improved cartilage delineation and precise T <sub>2</sub> values. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1275-1284