development of measures of polyneuropathy impairment in hattr amyloidosis from nis to mnis 7

Abstract Hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) is a rare, life-threatening disease, caused by point mutations in the transthyretin gene. It is a heterogeneous, multisystem disease with rapidly progressing polyneuropathy (including sensory, motor, and autonomic impairments) and cardiac dysfunction. Measures used to assess polyneuropathy in other diseases have been tested as endpoints in hATTR amyloidosis clinical trials (i.e. Neuropathy Impairment Score [NIS], NIS-lower limb, and NIS + 7), yet the unique nature of the polyneuropathy in this disease has necessitated modifications to these scales. In particular, the heterogeneous impairment and the aggressive disease course have been key drivers in developing scales that better capture the disease burden and progression of polyneuropathy in hATTR amyloidosis. The modified NIS + 7 (mNIS + 7) scale was specifically designed to assess polyneuropathy impairment in patients with hATTR amyloidosis, and has been the primary endpoint in two recent, phase III studies in this disease. The mNIS + 7 uses highly standardized, quantitative, and referenced assessments to quantify decreased muscle weakness, muscle stretch reflexes, sensory loss, and autonomic impairment. Physicians using this scale in clinical trials should be specifically trained and monitored to minimize variability. This article discusses the different scales that have been/are being used to assess polyneuropathy in patients with hATTR amyloidosis, their correlation with other disease assessments, and reflects on how and why scales have evolved to the latest iteration of mNIS + 7

Breaking CPT by mixed non-commutativity

The mixed component of the non-commutative parameter \theta_{\mu M}, where \mu = 0,1,2,3 and M is an extra dimensional index may violate four-dimensional CPT invariance. We calculate one and two-loop induced couplings of \theta_{\mu 5} with the four-dimensional axial vector current and with the CPT odd dim=6 operators starting from five-dimensional Yukawa and U(1) theories. The resulting bounds from clock comparison experiments place a stringent constraint on \theta_{\mu 5}, |\theta_{\mu 5}|^{-1/2} > 5\times 10^{11} GeV. The orbifold projection and/or localization of fermions on a 3-brane lead to CPT-conserving physics, in which case the constraints on \theta{\mu 5} are softened.Comment: 4 pages, latex, 1 figur

L'anémie à l'accouchement à Lomé (Togo) : prévalence, facteurs de risque et répercussions chez le nouveau-né

Une étude de prévalence réalisée à Lomé (Togo) a porté sur 125 couples mère-nouveau-né : 48% des mères et 30% des nouveaux-nés sont anémiques d'après les seuils de l'OMS. Trois mères sur quatre ont au moins un indicateur de carence en fer et celle-ci est le déterminant principal de l'anémie. Soixante huit pour cent ont une carence en folates, sans répercussion sur les paramètres hématologiques. Lorsque la carence en fer maternelle est grave (fer sérique <7umol), le fer sérique du nouveau-né est abaissé, ce qui témoigne d'une réduction de l'apport de fer au foetus. Le statut folique des nouveaux-nés est meilleur lorsque les mères ont reçu de l'acide folique pendant leur grossesse. Une supplémentation de ferro-folique systématique est donc nécessaire pendant la grossesse et serait bénéfique à la mère et à l'enfant. Les consultations prénatales devraient servir de cadre à la supplémentation. Leur fréquentation par 98% des femmes enceintes permet d'envisager une bonne couverture pour une telle intervention. (Résumé d'auteur

A List of Bright Interferometric Calibrators measured at the ESO VLTI

In a previous publication (Richichi & Percheron 2005) we described a program of observations of candidate calibrator stars at the ESO Very Large Telescope Interferometer (VLTI), and presented the main results from a statistical point of view. In the present paper, we concentrate on establishing a new homogeneous group of bright interferometric calibrators, based entirely on publicly available K-band VLTI observations carried out with the VINCI instrument up to July 2004. For this, we have defined a number of selection criteria for the quality and volume of the observations, and we have accordingly selected a list of 17 primary and 47 secondary calibrators. We have developed an approach to a robust global fit for the angular diameters using the whole volume of quality-controlled data, largely independent of a priori assumptions. Our results have been compared with direct measurements, and indirect estimates based on spectrophotometric methods, and general agreement is found within the combined uncertainties. The stars in our list cover the range K=-2.9 to +3.0 mag in brightness, and 1.3 to 20.5 milliarcseconds in uniform-disk diameter. The relative accuracy of the angular diameter values is on average 0.4% and 2% for the primary and secondary calibrators respectively. Our calibrators are well suited for interferometric observations in the near-infrared on baselines between ~20m and ~200m, and their accuracy is superior, at least for the primary calibrators, to other similar catalogues. Therefore, the present list of calibrators has the potential to lead to significantly improved interferometric scientific results

Quantum Logic with a Single Trapped Electron

We propose the use of a trapped electron to implement quantum logic operations. The fundamental controlled-NOT gate is shown to be feasible. The two quantum bits are stored in the internal and external (motional) degrees of freedom.Comment: 7 Pages, REVTeX, No Figures, To appear in Phys. Rev.

Social and physical environmental correlates of adults\u27 weekend sitting time and moderating effects of retirement status and physical health

Emerging research suggests that prolonged sedentary behaviour (SB) is detrimental to health. Changes in SB patterns are likely to occur during particular life stages, for example at retirement age (55-65-year-old). Evidence on socio-ecological SB correlates is scarce and inconsistent in this age group. Moreover, the influence of socio-ecological correlates may vary depending on health and retirement status. This study examined social and environment correlates of overall weekend day sitting among adults at or approaching retirement age, and moderating effects of perceived physical health and retirement status. Baseline data from the Wellbeing, Eating and Exercise for a Long Life study in 2839 Australian adults (55-65-year-old) were analysed. Participants self-reported proximal social factors, neighbourhood social and physical environment, physical health and retirement status. MLwiN multilevel regression analyses were conducted. In the multivariable model, only social support from friends/colleagues to discourage sitting (B = -0.891; p = 0.036) was associated with overall weekend day sitting. No moderation of retirement status, nor physical health were found in the multivariable results. Results from this study suggest the importance of social factors in relation to weekend day sitting among 55-65-year-old adults. Health promotion initiatives in this age group should pay special attention to enhancing social interaction opportunities. Moreover, findings suggest that SB-specific correlates may need to be examined in future research

Electron diffraction and high-resolution transmission electron microscopy of the high temperature crystal structures of GexSb2Te3+x (x=1,2,3) phase change material

The crystal structures of GeSb2Te4, Ge2Sb2Te5, and Ge3Sb2Te6 were determined using electron diffraction and high-resolution transmission electron microscopy. The structure determined for the former two crystals deviates from the ones proposed in the literature. These crystal structures were developed jointly upon cooling of liquid Ge2Sb2Te5. A stacking disorder parallel to the basal plane was observed that increases with increasing cooling rates. For the GexSb2Te3+x (x=1,2,3) crystals it is shown that an a,b,c stacking holds with an alternating stacking of x GeTe double layers identically present in binary GeTe and one Te-Sb-Te-Te-Sb- repeat unit also present in binary Sb2Te3. A stacking disorder is a logical consequence of building crystals with these two principal units. On the other hand, it is likely that all stable crystals of the Ge-Sb-Te systems are an ordered sequence of these two units. Some of the implications of these findings of the stable and metastable crystal structures that develop from amorphous Ge2Sb2Te5 are presented so as to understand the crucial crystallization process in Ge2Sb2Te5 phase change material

The Challenges of Living with and Caring for a Child or Children Affected by Neuronal Ceroid Lipofuscinosis Type 2 Disease: In-Depth Family Surveys in the United Kingdom and Germany

Limited research has investigated the challenges faced by families caring for children with neuronal ceroid lipofuscinosis type 2 (CLN2) disease. Face-to-face, mixed-method, in-depth surveys were conducted with 19 families (23 children) in the UK (n=9) and Germany (n=10) to assess the impact of caring for children with CLN2 disease, using national wellbeing and quality of life (QoL) measures. Primary (n=19) and secondary (n=10) caregivers, adult siblings (n=2), and child siblings (n=2) were included. Caregivers reported reduced health-related QoL compared with age and gender-matched controls (mean utility scores 0.08 and 0.11 lower in Germany and the UK, respectively). Hours of caregiving were significantly higher relative to that provided to a child of normal health, with stress, back pain, and reductions in sleep being recorded. Lower life satisfaction and happiness with partners were also reported, along with significant financial burden. Those caring for children in the late stage of disease were more greatly impacted than those with children in the rapidly progressive stage, or who were bereaved. The results of this study make clear the importance of emotional and practical support for caregivers and siblings coping with CLN2 disease